Medicine â€ș Urology

Periodontal Regeneration and Treatments

Description

This cluster of papers focuses on the applications of platelet-rich plasma (PRP) in regenerative medicine, particularly in the fields of orthopedic surgery and periodontal regeneration. The papers explore the use of PRP as a source of growth factors for tissue regeneration, its effectiveness in treating musculoskeletal injuries and osteoarthritis, and its potential as a biological agent for promoting healing and regeneration. Additionally, the cluster discusses the optimization and quantification of cytokines and growth factors in PRP for regenerative medicine.

Keywords

Platelet-Rich Plasma; Regenerative Medicine; Growth Factors; Tissue Regeneration; Orthopedic Surgery; Periodontal Regeneration; Biological Agents; Musculoskeletal Injuries; Osteoarthritis Treatment; Biomaterials

The aim of the present experiment was to study events involved in the healing of marginal, central and apical compartments of an extraction socket, from the formation of a blood 
 The aim of the present experiment was to study events involved in the healing of marginal, central and apical compartments of an extraction socket, from the formation of a blood clot, to bone tissue formation and remodeling of the newly formed hard tissue.Nine mongrel dogs were used for the experiment. The fourth mandibular premolars were selected for study and were divided into one mesial and one distal portion. The distal root was removed and the socket with surrounding soft and mineralized tissue was denoted "experimental unit". The dogs were killed 1, 3, 7, 14, 30, 60, 90, 120 and 180 days after the root extractions. Biopsies including the experimental units were demineralized in EDTA, dehydrated in ethanol and embedded in paraffin. Serial sections 7 microm thick were cut in a mesio-distal plane. From each biopsy, three sections representing the central part of the socket were selected for histological examination. Morphometric measurements were performed to determine the volume occupied by different types of tissues in the marginal, central and apical compartments of the extraction socket at different intervals.During the first 3 days of healing, a blood clot was found to occupy most of the extraction site. After seven days this clot was in part replaced with a provisional matrix (PCT). On day 14, the tissue of the socket was comprised of PM and woven bone. On day 30, mineralized bone occupied 88% of the socket volume. This tissue had decreased to 15% on day 180. The portion occupied by bone marrow (BM) in the day 60 specimens was about 75%, but had increased to 85% on day 180.The healing of an extraction socket involved a series of events including the formation of a coagulum that was replaced by (i) a provisional connective tissue matrix, (ii) woven bone, and (iii) lamellar bone and BM. During the healing process a hard tissue bridge--cortical bone--formed, which "closed" the socket.
In the oral cavity, an open growth system, bacterial adhesion to the non-shedding surfaces is for most bacteria the only way to survive. This adhesion occurs in 4 phases: the 
 In the oral cavity, an open growth system, bacterial adhesion to the non-shedding surfaces is for most bacteria the only way to survive. This adhesion occurs in 4 phases: the transport of the bacterium to the surface, the initial adhesion with a reversible and irreversible stage, the attachment by specific interactions, and finally the colonization in order to form a biofilm. Different hard surfaces are available in the oral cavity (teeth, filling materials, dental implants, or prostheses), all with different surface characteristics. In a healthy situation, a dynamic equilibrium exists on these surfaces between the forces of retention and those of removal. However, an increased bacterial accumulation often results in a shift toward disease. 2 mechanisms favour the retention of dental plaque: adhesion and stagnation. The aim of this review is to examine the influence of the surface roughness and the surface free energy in the adhesion process. Both in vitro and in vivo studies underline the importance of both variables in supragingival plaque formation. Rough surfaces will promote plaque formation and maturation, and high-energy surfaces are known to collect more plaque, to bind the plaque more strongly and to select specific bacteria. Although both variables interact with each other, the influence of surface roughness overrules that of the surface free energy. For the subgingival environment, with more facilities for microorganisms to survive, the importance of surface characteristics dramatically decreases. However, the influence of surface roughness and surface-free energy on supragingival plaque justifies the demand for smooth surfaces with a low surface-free energy in order to minimise plaque formation, thereby reducing the occurrence of caries and periodontitis.
The purpose of this study was to present the surgical procedures and the clinical results of guided tissue regeneration (GTR) treatment aimed at regenerating local jaw bone in situations where 
 The purpose of this study was to present the surgical procedures and the clinical results of guided tissue regeneration (GTR) treatment aimed at regenerating local jaw bone in situations where the anatomy of the ridge did not allow the placement of dental implants. 12 patients were selected for ridge enlargement or bony defect regeneration. A combined split‐ and full‐thickness flap was raised in areas designated for subsequent implant placement. Following perforation of the cortical bone to create a bleeding bone surface, a PTFE membrane was adjusted to the surgical site in such a way that a secluded space was created between the membrane and the subjacent bone surface in order to increase the width of the ridge or to regenerate bony defects present. Complete tension‐free closure of the soft tissue flap was emphasized. Following a healing period of 6 to 10 months, reopening procedures were performed and the gain of bone dimension was assessed. In 9 patients with 12 potential implant sites, a sufficient bone volume was obtained to allow subsequent implant placement. The gain of new bone formation varied between 1.5 and 5.5 mm. In 3 patients, acute infections developed which necessitated early removal of the membranes and no bone regeneration could be achieved. The results of the study indicate that the biological principle of GTR is highly predictable for ridge enlargement or defect regeneration under the prerequisite of a complication‐free healing.
Abstract The aim of the present study was to evaluate whether a regenerative surgical procedure, based on guided tissue regeneration, could predictably result in the formation of a new attachment 
 Abstract The aim of the present study was to evaluate whether a regenerative surgical procedure, based on guided tissue regeneration, could predictably result in the formation of a new attachment in human teeth. The material included 12 teeth in 10 patients with advanced periodontal disease. Following flap elevation, scaling, root planing and removal of granulation tissue, a teflon membrane was placed over the denuded root surface in such a way that the epithelium and the gingival connective tissue were prevented from reaching contact with the root during healing. The flap was replaced on the outer surface of the membrane and secured with interdental sutures. This design of wound preparation gives preference to the cells originating from the periodontal ligment (PDL‐cells) to repopulate the wound area adjacent to the root. Histologic analysis of the result of treatment was made in 5 of the 12 teeth scheduled for extraction. In the remaining 7 teeth, the result was evaluated using clinical measurements. The result of healing disclosed that in all teeth treated, substantial amounts of new attachment had formed. This suggests that predictable restitution of the attachment apparatus can be accomplished by using a method of treatment which is based on the principle of guided tissue regeneration.
Platelet concentrates for surgical topical applications are nowadays often used, but quantification of the long-term growth factor release from these preparations in most cases is impossible. Indeed, in most protocols, 
 Platelet concentrates for surgical topical applications are nowadays often used, but quantification of the long-term growth factor release from these preparations in most cases is impossible. Indeed, in most protocols, platelets are massively activated and there is no significant fibrin matrix to support growth factor release and cell migration. Choukroun's platelet-rich fibrin (PRF), a second generation platelet concentrate, is a leucocyte- and platelet-rich fibrin biomaterial. Here, we show that this dense fibrin membrane releases high quantities of three main growth factors (Transforming Growth Factor b-1 (TGFbeta-1), platelet derived growth factor AB, PDGF-AB; vascular endothelial growth factor, VEGF) and an important coagulation matricellular glycoprotein (thrombospondin-1, TSP-1) during 7 days. Moreover, the comparison between the final released amounts and the initial content of the membrane (after forcible extraction) allows us to consider that the leucocytes trapped in the fibrin matrix continue to produce high quantities of TGFbeta-1 and VEGF during the whole experimental time.
The objective of the present experiment was to study lesions in the peri‐implant and periodontal tissues resulting from ligature placement and subgingival plaque formation. The experiment was performed in 5 
 The objective of the present experiment was to study lesions in the peri‐implant and periodontal tissues resulting from ligature placement and subgingival plaque formation. The experiment was performed in 5 beagle dogs which at the start of the study were about 15 months old. They were given a diet which allowed gross plaque formation. The mandibular right premolars were extracted, 3 fixtures (a.m. BrĂ„nemark) installed and abutment connection performed. Towards the end of a 6‐month plaque control period, a clinical and radiographic examination was performed. Ligatures were placed in a subgingival position at 2 of the implants and the contralateral premolars. Plaque was allowed to accumulate. After 6 weeks, the ligatures were removed. 1 month later, the clinical and radiographical examination was repeated and samples from the subgingival microbiota obtained. Biopsies from the teeth and implant sites were harvested and processed for histometric and morphometric analyses. The results from the clinical and histological examinations revealed that:(i) clinical and radiographic signs of tissue destruction were more pronounced at implants than at teeth;(ii) the size of the soft tissue lesion was larger at implants than at teeth;(iii) the lesion at implants but 1 not at teeth extended into the bone marrow.
The utility of platelet-rich plasma (PRP) has spanned various fields of dermatology from chronic ulcer management to trichology and aesthetics, due to its role in wound healing. Though PRP is 
 The utility of platelet-rich plasma (PRP) has spanned various fields of dermatology from chronic ulcer management to trichology and aesthetics, due to its role in wound healing. Though PRP is being used over a long time, there is still confusion over proper terminology to define, classify and describe the different variations of platelet concentrates. There is also a wide variation in the reported protocols for standardization and preparation of PRP, in addition to lack of accurate characterization of the tested products in most articles on the topic. Additionally, the high cost of commercially available PRP kits, precludes its use over a larger population. <br>In this article, we review the principles and preparation methods of PRP based on available literature and place our perspective in standardizing a safe, simple protocol that can be followed to obtain an optimal consistent platelet yield.
Platelet-rich plasma is an autologous source of platelet-derived growth factor and transforming growth factor beta that is obtained by sequestering and concentrating platelets by gradient density centrifugation. This technique produced 
 Platelet-rich plasma is an autologous source of platelet-derived growth factor and transforming growth factor beta that is obtained by sequestering and concentrating platelets by gradient density centrifugation. This technique produced a concentration of human platelets of 338% and identified platelet-derived growth factor and transforming growth factor beta within them. Monoclonal antibody assessment of cancellous cellular marrow grafts demonstrated cells that were capable of responding to the growth factors by bearing cell membrane receptors. The additional amounts of these growth factors obtained by adding platelet-rich plasma to grafts evidenced a radiographic maturation rate 1.62 to 2.16 times that of grafts without platelet-rich plasma. As assessed by histomorphometry, there was also a greater bone density in grafts in which platelet-rich plasma was added (74.0% +/- 11%) than in grafts in which platelet-rich plasma was not added (55.1% +/- 8%; p = 0.005).
In this study we describe a principle for the accomplishment of bone regeneration based on the hypothesis that different cellular components in the tissue have varying rates of migration into 
 In this study we describe a principle for the accomplishment of bone regeneration based on the hypothesis that different cellular components in the tissue have varying rates of migration into a wound area during healing. By a mechanical hindrance, using a membrane technique, fibroblasts and other soft connective-tissue cells are prevented from entering the bone defect so that the presumably slower-migrating cells with osteogenic potential are allowed to repopulate the defect. Defects of standard size were created bilaterally through the man-dibular angles of rats. On one side of the jaw the defect was covered with Teflon membranes, whereas the defect on the other side served as control. Histologic analysis after healing demonstrated that on the test (membrane) side, half the number of animals showed complete bone healing after 3 weeks and all animals showed complete healing after 6 weeks. Little or no sign of healing was evident on the control side even after an observation period of 22 weeks.
Abstract The present study was designed to examine whether new attachment forms on root surfaces previously exposed to plaque by preventing the oral epithelium and the gingival connective tissue from 
 Abstract The present study was designed to examine whether new attachment forms on root surfaces previously exposed to plaque by preventing the oral epithelium and the gingival connective tissue from participating in the process of healing following treatment. 4 roots in each of 3 monkeys were used as test units while the roots of contralateral teeth served as controls. A surgical procedure was first used to expose the coronal half of the buccal root surfaces. Plaque was allowed to accumulate on the exposed surfaces for a period of 6 months. Subsequently, soft tissue flaps were raised and the root surfaces were carefully scaled and planed. The crowns of the test and control teeth were resected and the mucosal Haps were repositioned and sutured in such a way that the roots were properly covered. Immediately prior to suturing, membranes (Millipore¼ filter or Gore‐tex¼ membrane) were placed over the denuded root surfaces of the test teeth in order to prevent granulation tissue from the soft tissue flaps from reaching the roots during healing. The monkeys were sacrificed 3 months later. The jaws were removed and histological sections of test and control roots including their periodontal tissues were produced. New cementum with inserting collagen fibers was observed on the previously exposed surfaces of both test and control roots. However, the test surfaces exhibited considerably more new attachment than the control surfaces, indicating that the placement of the membrane favoured repopulation of the wound area adjacent to the roots by cells originating from the periodontal ligament.
Platelet-rich plasma (PRP) has been a breakthrough in the stimulation and acceleration of bone and soft tissue healing. It represents a relatively new biotechnology that is part of the growing 
 Platelet-rich plasma (PRP) has been a breakthrough in the stimulation and acceleration of bone and soft tissue healing. It represents a relatively new biotechnology that is part of the growing interest in tissue engineering and cellular therapy today. Because of its newness, there is a potential for misunderstanding, misuse, and application of what the practitioner may incorrectly think is PRP. The purpose of this paper is to discuss the definition of PRP, its safety, its proper development, and its most efficacious means of application. What is PRP? Platelet-rich plasma is just that; it is a volume of autologous plasma that has a platelet concentration above baseline. Normal platelet counts in blood range between 150,000/ÎŒl and 350,000/ÎŒl and average about 200,000/ÎŒl. Because the scientific proof of bone and soft tissue healing enhancement has been shown using PRP with 1,000,000 platelets/ÎŒl, it is this concentration of platelets in a 5-ml volume of plasma which is the working definition of PRP today. Lesser concentrations cannot be relied upon to enhance wound healing, and greater concentrations have not yet been shown to further enhance wound healing (Fig. 1).Fig. 1: Human platelet-derived growth factor AB (PDG-AB). Graph of PDGF-ab versus platelet count indicates growth factors available to tissues as directly proportional to the concentration of platelets.What is PRP in Relation to Recombinant Growth Factors? Because PRP is developed from autologous blood, it is inherently safe and is free from transmissible diseases such as HIV and hepatitis. Within PRP, the increased number of platelets delivers an increased number of growth factors to the surgical area. The seven known growth factors in PRP are: platelet derived growth factor aa (PDGFaa), PDGFbb, PDGFab, transforming growth factor beta-1 (TGF-b1), TGF-b2, vascular endothelial growth factor (VEGF), and epithelial growth factor (EGF). These are native growth factors in their biologically determined ratios. This is what distinguishes PRP from recombinant growth factors. Recombinant growth factors are pure human growth factors, but they are not native growth factors. Human cells such as platelets do not synthesize them. Instead they are synthesized usually by a culture of Chinese hamster ovarian cells that have a human gene inserted into their nucleus through a bacterial plasmid vector. Recombinant growth factors are single growth factors and are delivered in high doses within either a synthetic carrier or a carrier derived from processed animal proteins. PRP is the combination of seven native growth factors within a normal clot as the carrier. The clot is composed of fibrin, fibronectin, and vitronectin, which are cell adhesion molecules required for cell migration such as is seen in osteoconduction, wound epithelialization, and osseointegration. PRP, however, contains only the same concentrations of these cell adhesion molecules as does a normal blood clot (200 ÎŒg-400 ÎŒg/ml). Therefore, PRP is not a fibrin glue. Platelet Rich Plasma is also not osteoinductive. It cannot induce new bone formation de novo. Only the bone morphogenetic proteins (BMPs) are known to induce bone de novo. However, the prolonged length of time required by recombinant BMP to produce de novo new bone formation and its immature osteoid nature suggest an opportunity for PRP to accelerate BMP activity in the future. PRP acts on healing capable cells to increase their numbers (mitogenesis) and stimulate vascular ingrowth (angiogenesis). Therefore, it is unlikely to significantly promote bone substitutes and other non-cellular graft materials. However, because it has been shown to stimulate autogenous marrow grafts, it is likely to enhance the bone formation when applied to combinations of cellular autogenous bone and non-cellular bone substitutes. Terminology There has already been some mistaken terminology related to PRP. Some have advanced the term "platelet concentrate." This is not correct because a platelet concentrate is a solid composition of platelets without plasma, which would therefore not clot. The clinically useful product is a concentration of platelets in a small volume of plasma and is therefore a "platelet-rich plasma." Some have advanced the term "platelet gel." This is also incorrect because PRP is nothing more than a human blood clot with increased platelet numbers. The clot by virtue of its cell adhesion molecules has additional biologic activity, whereas a gel does not. Still others have reversed the term platelet-rich plasma into plasma rich in platelets, plasma very rich in platelets, and even plasma very very rich in platelets. The ludicrousness of this terminology is obvious and is more reminiscent of a coffee house than a clinical science. Processing PRP and PRP Devices The professions have already seen numerous individuals and corporations promoting devices to processes PRP for either cost savings or economic rewards. The practitioner should keep in mind that any PRP device should process a concentration of at least 1,000,000 platelets/ÎŒl in a 5-ml volume, process viable undamaged platelets, and process PRP in a sterile fashion and be pyrogen free. Liability, consent, and licensing must be discussed because both patient and auxiliary staff safety issues are pertinent. It should be noted that "sterile" and "pyrogen free" are not the same. Sterile means the absence of microorganism. Pyrogen free means the absence of any microorganism products or foreign body particle that might produce a fever. Therefore, the PRP device must use only certified pyrogen free disposable materials. To truly concentrate platelets from autologous blood, the device must use a double centrifugation technique. The first spin (called the hard spin) will separate the red blood cells from the plasma, which contains the platelets, the white blood cells, and the clotting factors. The second spin (called the soft spin) finely separates the platelets and white blood cells together with a few red blood cells from the plasma. This soft spin produces the PRP and separates it from the platelet poor plasma (PPP) free from the obstruction provided by a large number of red blood cells. To attempt PRP with a single spin would not produce a true PRP. Instead, it would produce a mixture of PRP and PPP and have disappointingly low platelet counts. Regardless of the rate of centrifugation or the time of centrifugation, a single spin cannot adequately concentrate platelets, because the red blood cells will interfere with the fine separation of the platelets. This is germane to those who may use a laboratory centrifuge to develop PRP or may purchase a device that is merely a modification of laboratory centrifuge. Such centrifuges are designed for diagnostic purposes—not PRP development. They may not produce a sufficient platelet yield, they may damage platelets, they may not use pyrogen free test tubes, and they are not FDA cleared. Therefore, they should not be used. The FDA clearance is indeed important. Although the patient is protected from transmissible diseases because of the autologous nature of PRP, the practitioner and the auxiliary staff are not. Devices that leak blood or have the potential to malfunction from centrifuge misbalance, or design characteristic intended for diagnostic blood work, are a real health, medical, and legal risk. Practitioners are recommended to look to devices that have the simple FDA clearance to process PRP from autologous whole blood. Further FDA clearances to mix PRP with autologous grafts and bone substitutes is an advanced security of some devices. No dental practitioner or medical practitioner is licensed to infuse or re-infuse blood or blood products systemically in an office setting. However, it is within the licensure of each to apply blood products topically in the office as is done with PRP. Office devices that produce PRP use only 45 ml to 60 ml of blood, which is insignificant related to a normal 4- to 5-L blood volume. There is no reason to re-infuse the blood that is not used, and it would be risky to do so. Applications of PRP PRP may be mixed into a bone graft, layered in as the graft is placed, sprayed on a soft tissue surface, applied on top of a graft, or used as a biologic membrane. However, clotting of the PRP should be done only at the time of use. Clotting activates platelets, which begin secreting their growth factors immediately (Fig. 2). Within 10 minutes they secrete 70% of their stored growth factors and close to 100% within the first hour (Fig. 3). They then synthesize additional amounts of growth factors for about 8 days until they are depleted and die. Therefore, clinicians should only clot (activate) PRP when they are ready to use it and not in advance. Clinicians should also critically assess publications, which may claim to study PRP but are actually studying growth factor depleted clots or supernatants. Complete PRP is both a fresh clot and the supernatant.Fig. 2: Platelet-rich plasma (PRP) membrane is an activation of the clotting mechanism, which in turn activates platelets and stimulates the release of their growth factors.Fig. 3: Graph of PDGF-bb versus time indicating the release of 90% of the growth factors within the first 10 minutes of clot activation and the remainder within the first 1 to 11/2 hours.This knowledge is germane to those who have advanced the concept of developing PRP from clotted blood or to companies that have promoted "serum separator tubes." Serum is not plasma and contains almost no platelets. It is impossible to develop PRP from clotted whole blood. Because the two functional roles of platelets in nature are initiation of healing and hemostasis, platelets become part of the physical blood clot and, therefore, the serum is devoid of platelets. PRP can only be developed from anticoagulated blood. Which Anticoagulant to Use? There are several choices of anticoagulants the clinician can use. However, only two support the metabolic needs of platelets and the viable separation of platelets in an undamaged manner. Anticoagulant citrate dextrose-A (ACD-A) is preferred and will best support platelet viability. The citrate binds calcium to create the anticoagulation. The dextrose, buffers, and other ingredients support platelet metabolism. ACD-A is the anticoagulant used to store viable platelets for platelet transfusions from blood banks. Citrate Phosphate Dextrose (CPD) is also useful for PRP development. It is similar to ACD-A but has fewer supportive ingredients and, therefore, is 10% less effective in maintaining platelet viability. Growth Factors, PRP, and Cancer Because growth factors stimulate cellular proliferation, some have advanced a concern that the recombinant BMP's and PRP might stimulate cancers. Actually, no growth factor can provoke a cancer. All growth factors act on cell membranes, not the cell nucleus. Growth factors activate an internal cytoplasmic signal protein, which promotes a normal gene expression, not an abnormal gene expression. Growth factors are not mutagens, unlike true carcinogens such as radiation, tobacco anthracene tars, UV light, etc. Instead growth factors are normal body proteins. The security specifically related to PRP and cancer is that PRP is nothing more than the same blood clot that would be in any normal wound, except it contains a greater number of platelets. Clinical Development and Use of PRP PRP is best developed from autogenous whole blood shortly before or at the very beginning of the surgical procedure. This is because platelets will collect at the surgical site to initiate clotting and healing. This will reduce the whole blood platelet count somewhat. In addition, during surgery intravenous fluid will dilute whole blood, further reducing platelet numbers. Once developed, PRP is stable and remains sterile in the anticoagulated state for 8 hours. Therefore, with longer surgeries PRP is just as effective and sterile as it would be if used immediately. However, the PRP must be separated from the PPP soon after centrifugation because the concentrated platelets will slowly diffuse into the PPP over time and would reduce the platelet count of the PRP preparation. Specific Clinical Uses In implant dentistry, the most obvious application of PRP would be to accelerate autogenous grafts used for site preparations, sinus lifts, osseointegrations, ridge augmentations, etc. (Figs. 4 and 5). To date, no positive clinical benefits have been documented, nor can be expected, with the use of PRP with non-vital bone substitutes. The target of PRP remains viable osteoprogenitor cells and stem cells. However, an enhanced bone regeneration can be expected when PRP is used with mixtures of autogenous bone and bone substitutes and with recombinant human growth factors such as recombinant BMP.Fig. 4: Severe vertical maxillary ridge defect before bone grafting with PRP enhancement of bone formation. Fig. 5. Three months after bone graft reconstruction enhanced with PRP, a mature graft is capable of receiving dental implants with excellent primary stability.In addition, early results are promising that PRP placed in the preparation site of a dental implant will promote and accelerate osseointegration. This may be of specific benefit in the maxilla, in areas of previous failures, in type IV bone, in the osteoporotic woman, etc. Soft tissue healing enhancement and rapid epithelialization of skin with PRP has already been documented. The extrapolation is apparent to the soft tissue-healing enhancement to palatal grafts, gingival flaps, and cosmetic dentistry soft tissue augmentations. Growth factors in general and PRP in particular are part of a new biotechnology with already established efficacy and future potential. It is the responsibility of the clinician to gain a thorough understanding of this biotechnology and to use it correctly and wisely for the benefit of our patients, who trust our judgment. It is hoped that this paper served that end to some degree.
T he purpose of this study was to evaluate the clinical effectiveness of a bioabsorbable membrane made of glycolide and lactide polymers in preserving alveolar ridges following tooth extraction using 
 T he purpose of this study was to evaluate the clinical effectiveness of a bioabsorbable membrane made of glycolide and lactide polymers in preserving alveolar ridges following tooth extraction using a surgical technique based on the principles of guided bone regeneration. Sixteen patients requiring extractions of 2 anterior teeth or bicuspids participated in the study (split‐mouth design). Following elevation of buccal and lingual full‐thickness flaps and extraction of teeth, experimental sites were covered with bioabsorbable membranes; control sites did not receive any membrane. Titanium pins served as fixed reference points for measurements. Flaps were advanced in order to achieve primary closure of the surgical wound. No membrane became exposed in the course of healing. Reentry surgeries were performed at 6 months. Results showed that experimental sites presented with significantly less loss of alveolar bone height, more internal socket bone fill, and less horizontal resorption of the alveolar bone ridge. This study suggests that treatment of extraction sockets with membranes made of glycolide and lactide polymers is valuable in preserving alveolar bone in extraction sockets and preventing alveolar ridge defects. J Periodontol 1998;69:1044–1049 .
Studies during the last 20 years have indicated that enamel-related proteins are involved in the formation of cementum. In the present article, this relation is further explored. Attention is called 
 Studies during the last 20 years have indicated that enamel-related proteins are involved in the formation of cementum. In the present article, this relation is further explored. Attention is called to the fact that coronal acellular extrinsic fiber cementum is formed on the enamel surface in a number of species. The composition of the enamel matrix proteins and the expression of these proteins during root formation are briefly reviewed. The dominating constituent of the enamel matrix, amelogenin, is shown by means of immunohistochemistry to be expressed in human teeth during root formation. Amelogenin was also found to be present in Tomes' granular layer of human teeth. When mesenchymal cells of the dental follicle were exposed to the enamel matrix a non-cellular hard tissue matrix was formed at the enamel surface. Application of porcine enamel matrix in experimental cavities in the roots of incisors of monkeys induced formation of acellular cementum that was well attached to the dentin. In control cavities without enamel matrix, a cellular, poorly attached hard tissue was formed. The present studies provide additional support to the idea that enamel matrix proteins are involved in the formation of acellular cementum and also that they have the potential to induce regeneration of the same type of cementum.
Platelet-rich plasma (PRP) has been utilized in surgery for 2 decades; there has been a recent interest in the use of PRP for the treatment of sports-related injuries. PRP contains 
 Platelet-rich plasma (PRP) has been utilized in surgery for 2 decades; there has been a recent interest in the use of PRP for the treatment of sports-related injuries. PRP contains growth factors and bioactive proteins that influence the healing of tendon, ligament, muscle, and bone. This article examines the basic science of PRP, and it describes the current clinical applications in sports medicine. This study reviews and evaluates the human studies that have been published in the orthopaedic surgery and sports medicine literature. The use of PRP in amateur and professional sports is reviewed, and the regulation of PRP by antidoping agencies is discussed.
Growth factors released from activated platelets initiate and modulate wound healing in both soft and hard tissues. A recent strategy to promote the wound-healing cascade is to prepare an autologous 
 Growth factors released from activated platelets initiate and modulate wound healing in both soft and hard tissues. A recent strategy to promote the wound-healing cascade is to prepare an autologous platelet concentrate suspended in plasma, also known as platelet-rich plasma, that contains growth factors and administer it to wound sites. The purpose of this study was to quantitate platelet number and growth factors released from a prepared platelet concentrate. Whole blood was drawn from 10 healthy patients undergoing cosmetic surgery and concentrated into platelet-rich plasma. Platelet counts on whole blood and platelet-rich plasma were determined using a Cell-Dyn 3200. Platelet-derived growth factor-BB, transforming growth factor-beta1, vascular endothelial growth factor, endothelial growth factor, and insulin-like growth factor-1 were measured in the platelet-rich plasma using the enzyme-linked immunosorbent assay method. In addition, platelet activation during the concentration procedure was analyzed by measuring P selectin values in blood serum. An 8-fold increase in platelet concentration was found in the platelet-rich plasma compared with that of whole blood (baseline whole blood, 197 +/- 42 x 10 platelets/microl; platelet concentrate, 1600 +/- 330 x 10 platelets/microl). The concentration of growth factors also increased with increasing platelet number. However, growth factor concentration varied from patient to patient. On average for the whole blood as compared with platelet-rich plasma, the platelet-derived growth factor-BB concentration increased from 3.3 +/- 0.9 ng/ml to 17 +/- 8 ng/ml, transforming growth factor-beta1 concentration increased from 35 +/- 8 ng/ml to 120 +/- 42 ng/ml, vascular endothelial growth factor concentration increased from 155 +/- 110 pg/ml to 955 +/- 1030 pg/ml, and endothelial growth factor concentration increased from 129 +/- 61 pg/ml to 470 +/- 320 pg/ml. No increase was found for insulin-like growth factor-1. In addition, no increase in platelet activation occurred during the concentration procedure as determined by the platelet surface receptor P selectin (45 +/- 16 pg/ml to 52 +/- 11 pg/ml, p = 0.65). In conclusion, a variety of potentially therapeutic growth factors were detected and released from the platelets in significant levels in platelet-rich plasma preparations. Sufficient concentrates and release of these growth factors through autologous platelet gels may be capable of expediting wound healing in a variety of as yet undetermined specific wound applications.
The present experiment was undertaken to test the hypothesis that new connective tissue attachment may form on a previously periodontitis involved root surface provided cells originating from the periodontal ligament 
 The present experiment was undertaken to test the hypothesis that new connective tissue attachment may form on a previously periodontitis involved root surface provided cells originating from the periodontal ligament are enabled to repopulate the root surface during healing. A mandibular incisor with advanced periodontal disease of long standing (the distance between the cemento-enamel junction and the alveolar bone crest was 9 mm) was subjected to periodontal surgery using a technique which during healing prevented the dentogingival epithelium and the gingival connective tissue from reaching contact with the curetted root surface. Preference was hereby given to the periodontal ligament cells to repopulate the previously diseased root surface. After 3 months of healing a block biopsy containing the incisor and surrounding tissue was sampled. The histological analysis revealed that new cementum with inserting principal fibers had formed on the previously diseased root surface. This new attachment extended in coronal direction to a level 5 mm coronal to the alveolar bone crest. This finding suggests that new attachment can be achieved by cells originating from the periodontal ligament and demonstrates that the concept that the periodontitis affected root surface is a major preventive factor for new attachment is invalid.
The aim of the present study was to examine if new cementum and new attachment may form during healing of a wound prepared in such a way that preference is 
 The aim of the present study was to examine if new cementum and new attachment may form during healing of a wound prepared in such a way that preference is given to periodontal ligament cells to repopulate the wound area adjacent to a root which has been surgically deprived of its periodontal ligament and cementum layer. The maxillary lateral incisors and mandibular canines in three monkeys were used for experimentation. Following elevation of a mucoperiosteal flap, the buccal and approximal alveolar bone was removed within an area extending from the mid-root level to a level 2 mm apical to the marginal bone crest. Following bone removal, the root surfaces were curetted in order to remove the cementum layer. Notches were prepared in the roots to demarcate the denuded root portion. Prior to repositioning of the tissue flap a millipore filter was placed over the treated area in order to prevent the gingival connective tissue from coming into contact with the root surface during healing. The animals were sacrificed 6 months after surgery. The jaws were removed and histological sections of the experimental teeth and surrounding periodontal tissues were produced. New cementum with inserting collagen fibers was observed on the curetted root surfaces. However, this result of healing did not consistently occur along the entire length of the curetted root portion. In the coronal part of the wound, healing was frequently characterized by connective tissue adhesion to the root surface without signs of cementum formation and fibrous attachment. The results of the experiment suggest that the periodontal ligament cells possess the ability to reestablish connective tissue attachment.
Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its 
 Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed.PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure.Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 10(6) to 1.9 × 10(6) platelets/ÎŒl). Platelets were highly purified, because only <0.3% from the initial red blood cells and leukocytes was present in the final PRP preparation. We also quantified growth factors, cytokines and chemokines secreted by the concentrated platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-ÎČ3 and IFNÎł were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of several growth factors, including platelet-derived growth factor and TGF.Our study resulted in a consistent PRP preparation method that yielded a cytokine and growth factor pool from different donors with high reproducibility. These findings support the use of PRP in therapies aiming for tissue regeneration, and its content characterization will allow us to understand and improve the clinical outcomes.
This article presents preliminary clinical evidence of the beneficial effect of the use of plasma rich in growth factors of autologous origin. The plasma is obtained from the individual patient 
 This article presents preliminary clinical evidence of the beneficial effect of the use of plasma rich in growth factors of autologous origin. The plasma is obtained from the individual patient by plasmapheresis. The macroscopic and microscopic results obtained with bone regeneration using this technique, which uses no membrane or barrier, can be observed. The incorporation of these concepts can introduce several advantages, including the enhancement and acceleration of bone regeneration and more rapid and predictable soft tissue healing.
Choukroun's platelet-rich fibrin (PRF) is obtained from blood without adding anticoagulants. In this study, protocols for standard platelet-rich fibrin (S-PRF) (2700 rpm, 12 minutes) and advanced platelet-rich fibrin (A-PRF) (1500 
 Choukroun's platelet-rich fibrin (PRF) is obtained from blood without adding anticoagulants. In this study, protocols for standard platelet-rich fibrin (S-PRF) (2700 rpm, 12 minutes) and advanced platelet-rich fibrin (A-PRF) (1500 rpm, 14 minutes) were compared to establish by histological cell detection and histomorphometrical measurement of cell distribution the effects of the centrifugal force (speed and time) on the distribution of cells relevant for wound healing and tissue regeneration. Immunohistochemistry for monocytes, T and B -lymphocytes, neutrophilic granulocytes, CD34-positive stem cells, and platelets was performed on clots produced from four different human donors. Platelets were detected throughout the clot in both groups, although in the A-PRF group, more platelets were found in the distal part, away from the buffy coat (BC). T- and B-lymphocytes, stem cells, and monocytes were detected in the surroundings of the BC in both groups. Decreasing the rpm while increasing the centrifugation time in the A-PRF group gave an enhanced presence of neutrophilic granulocytes in the distal part of the clot. In the S-PRF group, neutrophils were found mostly at the red blood cell (RBC)-BC interface. Neutrophilic granulocytes contribute to monocyte differentiation into macrophages. Accordingly, a higher presence of these cells might be able to influence the differentiation of host macrophages and macrophages within the clot after implantation. Thus, A-PRF might influence bone and soft tissue regeneration, especially through the presence of monocytes/macrophages and their growth factors. The relevance and feasibility of this tissue-engineering concept have to be proven through in vivo studies.
Platelets are known for their role in haemostasis where they help prevent blood loss at sites of vascular injury. To do this, they adhere, aggregate and form a procoagulant surface 
 Platelets are known for their role in haemostasis where they help prevent blood loss at sites of vascular injury. To do this, they adhere, aggregate and form a procoagulant surface leading to thrombin generation and fibrin formation. Platelets also release substances that promote tissue repair and influence the reactivity of vascular and other blood cells in angiogenesis and inflammation. They contain storage pools of growth factors including PDGF, TGF-beta?and VEGF as well as cytokines including proteins such as PF4 and CD40L. Chemokines and newly synthesised active metabolites are also released. The fact that platelets secrete growth factors and active metabolites means that their applied use can have a positive influence in clinical situations requiring rapid healing and tissue regeneration. Their administration in fibrin clot or fibrin glue provides an adhesive support that can confine secretion to a chosen site. Additionally,the presentation of growth factors attached to platelets and/or fibrin may result in enhanced activity over recombinant proteins. Dental implant surgery with guided bone regeneration is one situation where an autologous platelet-rich clot clearly accelerates ossification after tooth extraction and/or around titanium implants. The end result is both marked reductions in the time required for implant stabilisation and an improved success rate. Orthopaedic surgery, muscle and/or tendon repair, reversal of skin ulcers, hole repair in eye surgery and cosmetic surgery are other situations where autologous plate-lets accelerate healing. Our aim is to review these advances and discuss the ways in which platelets may provide such unexpected beneficial therapeutic effects.
Specific growth factors have been proposed as therapeutic proteins for cartilage repair.Platelet-rich plasma (PRP) provides symptomatic relief in early osteoarthritis (OA) of the knee.Randomized controlled trial; Level of evidence, 1.A 
 Specific growth factors have been proposed as therapeutic proteins for cartilage repair.Platelet-rich plasma (PRP) provides symptomatic relief in early osteoarthritis (OA) of the knee.Randomized controlled trial; Level of evidence, 1.A total of 78 patients (156 knees) with bilateral OA were divided randomly into 3 groups. Group A (52 knees) received a single injection of PRP, group B (50 knees) received 2 injections of PRP 3 weeks apart, and group C (46 knees) received a single injection of normal saline. White blood cell (WBC)-filtered PRP with a platelet count 3 times that of baseline (PRP type 4B) was administered in all. All the groups were homogeneous and comparable in baseline characteristics. Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire before treatment and at 6 weeks, 3 months, and 6 months after treatment. They were also evaluated for pain by a visual analog scale, and overall satisfaction with the procedure and complications were noted.Statistically significant improvement in all WOMAC parameters was noted in groups A and B within 2 to 3 weeks and lasting until the final follow-up at 6 months, with slight worsening at the 6-month follow-up. The mean WOMAC scores (pain, stiffness, physical function, and total score) for group A at baseline were 10.18, 3.12, 36.56, and 49.86, respectively, and at final follow-up were 5.00, 2.10, 20.08, and 27.18, respectively, showing significant improvement. Similar improvement was noted in group B (mean WOMAC scores at baseline: 10.62, 3.50, 39.10, and 53.20, respectively; mean WOMAC scores at final follow-up: 6.18, 1.88, 22.40, and 30.48, respectively). In group C, the mean WOMAC scores deteriorated from baseline (9.04, 2.70, 33.80, and 45.54, respectively) to final follow-up (10.87, 2.76, 39.46, and 53.09, respectively). The 3 groups were compared with each other, and no improvement was noted in group C as compared with groups A and B (P < .001). There was no difference between groups A and B, and there was no influence of age, sex, weight, or body mass index on the outcome. Knees with Ahlback grade 1 fared better than those with grade 2. Mild complications such as nausea and dizziness, which were of short duration, were observed in 6 patients (22.2%) in group A and 11 patients (44%) in group B.A single dose of WBC-filtered PRP in concentrations of 10 times the normal amount is as effective as 2 injections to alleviate symptoms in early knee OA. The results, however, deteriorate after 6 months. Both groups treated with PRP had better results than did the group injected with saline only.
Abstract For many years, operative dentistry has been using regenerative approaches to treat dental disease. The use of calcium hydroxide to stimulate reparative or reactionary dentin is clearly an example 
 Abstract For many years, operative dentistry has been using regenerative approaches to treat dental disease. The use of calcium hydroxide to stimulate reparative or reactionary dentin is clearly an example of such a therapeutic strategy. The advent of tissue engineering is allowing dentistry to move forward in the use of regeneration as an underlying principle for the treatment of dental disease. Tissue engineering is a multi-disciplinary science that brings together biology, engineering and clinical sciences with developing new tissues and organs. It is based on fundamental principles that involve the identification of appropriate cells, the development of conducive scaffolds and an understanding of the morphogenic signals required to induce cells to regenerate the tissues that were lost. This review is focused on the presentation and discussion of existing literature that covers the engineering of enamel, dentin and pulp, as well on the engineering of entire teeth. There are clearly major roadblocks to overcome before such strategies move to the clinic and are used regularly to treat patients. However, existing evidence strongly suggests that the engineering of new dental structures to replace tissues lost during the process of caries or trauma will have a place in the future of operative dentistry.
Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood 
 Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-ÎČ, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches. The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research.
The aim of the present clinical trial was to compare the long-term effect of EMDOGAIN treatment as an adjunct to modified widman flap (MWF) surgery with the effect of MWF 
 The aim of the present clinical trial was to compare the long-term effect of EMDOGAIN treatment as an adjunct to modified widman flap (MWF) surgery with the effect of MWF and placebo treatment. The investigation was a placebo-controlled, randomized multicenter trial involving 33 subjects with 34 paired test and control sites. The protocol required 2 interproximal sites, appropriately separated, in the same jaw with probing pocket depths > or = 6 mm and an associated intrabony defect with a depth of > or = 4 mm and a width of > or = 2 mm as measured on a radiograph. Only predominantly 1- and 2-wall defects were included. Clinical attachment gain and radiographic bone gain were used as primary outcome variables. Assessments were made at baseline, 8, 16 and 36 months. Mean values for clinical attachment level gain in test and control sites at 8 months were 2.1 mm and 1.5 mm, respectively; at 16 months, 2.3 mm and 1.7 mm, respectively; and at 36 months 2.2 mm and 1.7 mm, respectively; and the differences were statistically significantly different at each time point (p < 0.01). The radiographic bone level continued to increase over the 36 months at the EMDOGAIN-treated sites, while it remained close to the baseline level at the control sites. The statistically significant (p < 0.001) radiographic bone gain at 36 months of 2.6 mm at EMDOGAIN-treated sites corresponded to 36% gain of initial bone loss or 66% defect fill. The present trial has demonstrated that topical application of EMDOGAIN onto diseased root surfaces associated with intrabony defects during MWF periodontal surgery will promote an increased gain of radiographic bone and clinical attachment compared to control (placebo application) surgery in the same patient. There was no evidence to indicate any clinical adverse effects from application of EMDOGAIN conjunction with periodontal surgery.
An index to assess the size of the interproximal gingival papillae adjacent to single implant restorations was described and preliminary tested in a pilot study of retrospective material comprising 25 
 An index to assess the size of the interproximal gingival papillae adjacent to single implant restorations was described and preliminary tested in a pilot study of retrospective material comprising 25 crowns in 21 patients. The result indicated a significant spontaneous regeneration of papillae (P < .001) after a mean follow-up period of 1.5 years. Based on these results, the general conclusion was made that the proposed index allows scientific assessment of soft tissue contour adjacent to single-implant restorations. The results also indicated that soft tissue changed in a systematic manner during the time period between insertion of the crowns and follow-up 1 to 3 years later.
Platelet-rich plasma (PRP) is currently used in different medical fields. The interest in the application of PRP in dermatology has recently increased. It is being used in several different applications 
 Platelet-rich plasma (PRP) is currently used in different medical fields. The interest in the application of PRP in dermatology has recently increased. It is being used in several different applications as in tissue regeneration, wound healing, scar revision, skin rejuvenating effects, and alopecia. PRP is a biological product defined as a portion of the plasma fraction of autologous blood with a platelet concentration above the baseline. It is obtained from the blood of patients collected before centrifugation. The knowledge of the biology, mechanism of action, and classification of the PRP should help clinicians better understand this new therapy and to easily sort and interpret the data available in the literature regarding PRP. In this review, we try to provide useful information for a better understanding of what should and should not be treated with PRP.
Bone replacement might have been practiced for centuries with various materials of natural origin, but had rarely met success until the late 19th century. Nowadays, many different bone substitutes can 
 Bone replacement might have been practiced for centuries with various materials of natural origin, but had rarely met success until the late 19th century. Nowadays, many different bone substitutes can be used. They can be either derived from biological products such as demineralized bone matrix, platelet-rich plasma, hydroxyapatite, adjunction of growth factors (like bone morphogenetic protein) or synthetic such as calcium sulfate, tri-calcium phosphate ceramics, bioactive glasses, or polymer-based substitutes. All these substitutes are not suitable for every clinical use, and they have to be chosen selectively depending on their purpose. Thus, this review aims to highlight the principal characteristics of the most commonly used bone substitutes and to give some directions concerning their clinical use, as spine fusion, open-wedge tibial osteotomy, long bone fracture, oral and maxillofacial surgery, or periodontal treatments. However, the main limitations to bone substitutes use remain the management of large defects and the lack of vascularization in their central part, which is likely to appear following their utilization. In the field of bone tissue engineering, developing porous synthetic substitutes able to support a faster and a wider vascularization within their structure seems to be a promising way of research.
Plastome (plastid genome) sequences provide valuable information for understanding the phylogenetic relationships and evolutionary history of plants. Although the rapid development of high-throughput sequencing technology has led to an explosion 
 Plastome (plastid genome) sequences provide valuable information for understanding the phylogenetic relationships and evolutionary history of plants. Although the rapid development of high-throughput sequencing technology has led to an explosion of plastome sequences, annotation remains a significant bottleneck for plastomes. User-friendly batch annotation of multiple plastomes is an urgent need.We introduce Plastid Genome Annotator (PGA), a standalone command line tool that can perform rapid, accurate, and flexible batch annotation of newly generated target plastomes based on well-annotated reference plastomes. In contrast to current existing tools, PGA uses reference plastomes as the query and unannotated target plastomes as the subject to locate genes, which we refer to as the reverse query-subject BLAST search approach. PGA accurately identifies gene and intron boundaries as well as intron loss. The program outputs GenBank-formatted files as well as a log file to assist users in verifying annotations. Comparisons against other available plastome annotation tools demonstrated the high annotation accuracy of PGA, with little or no post-annotation verification necessary. Likewise, we demonstrated the flexibility of reference plastomes within PGA by annotating the plastome of Rosa roxburghii using that of Amborella trichopoda as a reference. The program, user manual and example data sets are freely available at https://github.com/quxiaojian/PGA.PGA facilitates rapid, accurate, and flexible batch annotation of plastomes across plants. For projects in which multiple plastomes are generated, the time savings for high-quality plastome annotation are especially significant.
Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet 
 Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects, and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.
Osteoarthritis (OA) is a widespread joint disease characterized by the gradual loss of cartilage. Intra-articular injections, including platelet-rich plasma (PRP), are commonly used for treatment, but the optimal PRP preparation 
 Osteoarthritis (OA) is a widespread joint disease characterized by the gradual loss of cartilage. Intra-articular injections, including platelet-rich plasma (PRP), are commonly used for treatment, but the optimal PRP preparation method remains debated. This study aims to perform a network meta-analysis of randomized controlled trials to compare the efficacy of different PRP preparation methods and determine the most effective protocols. The literature search was conducted based on PRISMA guidelines. Randomized controlled trials (RCTs) evaluating intra-articular injectables in osteoarthritic knees were included. Data were extracted, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were analyzed at 3, 6, and 12-18 months. Clinical outcomes were compared using a frequentist network meta-analysis, and treatment options were ranked using the P-Score. Statistical analysis was performed using R 4.3.2. Twenty-three RCTs with 1752 patients were included. Treatments included PRP, plasma rich in growth factor (PRGF), leukocyte-poor PRP (LP-PRP), leukocyte-rich PRP (LR-PRP), hyaluronic acid (HA), and saline placebo. Leukocyte-rich PRP with low platelet concentration increase, using both anticoagulant and activator showed the best effects on WOMAC pain and stiffness scores within 6 months (WMD = 26.02; 95% CrI, 0.92-52.46). Leukocyte-poor PRP with high platelet concentration increase, using anticoagulant without activator was most effective for WOMAC function and stiffness at 12-18 months (WMD = 18.94; 95% CrI, 8.34-28.12). Long-term results indicated Leukocyte-poor PRP with low platelet concentration increase, using anticoagulant without activator yielded the best outcomes for cartilage repair and function (WMD = 17.09; 95% CrI, -8.4 to 42.78). Optimizing OA treatment involves tailoring PRP protocols to disease stage, with low platelet, high leukocyte PRP (RPRP_LPC_Y_Y) recommended for early OA due to its anti-inflammatory effects and high platelet, low leukocyte PRP (PPRP-HPC) preferred for advanced OA to promote tissue repair and regeneration.
Lana Micko , Äąirts Ć alms | International Journal of Oral and Maxillofacial Surgery
Background/Objectives: Periodontal and implant therapies frequently require soft tissue augmentation for optimal outcomes. As the hard palate serves as the primary donor site, this study evaluated palatal masticatory mucosa thickness 
 Background/Objectives: Periodontal and implant therapies frequently require soft tissue augmentation for optimal outcomes. As the hard palate serves as the primary donor site, this study evaluated palatal masticatory mucosa thickness variations in a Saudi population of the Eastern Province using cone-beam computed tomography (CBCT) at a teaching dental hospital, providing site-specific data for clinical applications. Methods: A retrospective cross-sectional analysis of 215 CBCT scans from systemically healthy, non-smoking adults (&gt;18 years) was conducted at the University Dental Hospital. Measurements were taken at 12 standardized sites (3 mm, 6 mm, and 9 mm from the cementoenamel junction) across maxillary canines, premolars, and first molars. Statistical analysis included Friedman’s test and t-tests. Results: Significant site variations were observed, with the second premolar region showing greatest thickness (3.48 ± 0.80 mm at 9 mm) and the first molar region the lowest (1.88 ± 0.63 mm at 3 mm) (p &lt; 0.001). Mucosal thickness generally increased coronally to apically (p &lt; 0.001). Age &gt;35 years correlated with significantly thicker mucosa (p &lt; 0.05), while no statistically significant gender-based differences were observed for all sites (p &gt; 0.05). Conclusions: CBCT provides reliable, non-invasive assessment of palatal mucosa thickness. These findings offer region-specific data for consideration in periodontal and implant procedures involving soft tissue grafting.
Injectable platelet-rich fibrin (i-PRF) features a higher concentration of growth factor and lower viscosity compared with PRF, making it advantageous for periodontal regenerative therapy. However, its low mechanical property and 
 Injectable platelet-rich fibrin (i-PRF) features a higher concentration of growth factor and lower viscosity compared with PRF, making it advantageous for periodontal regenerative therapy. However, its low mechanical property and high degradation rate cause its limited usage in bone augmentation. Hydrogel interacts with i-PRF, which is expected to replace bone graft considering its disadvantages. Through the synergistic effects of the materials, a sustained release of growth factor is achieved, promoting bone formation and maturation.Osteogenic markers, including alkaline phosphatase (ALP) activity and calcium deposition, were measured at intervals of 1, 7, 14, and 21 days using osteoblast-like cells. In vivo study using the extraction socket of Wistar rat applied with the same material was also done and measured at 21 and 42 days. The study included three groups: hydrogel i-PRF, bone graft (FDBA) i-PRF, and a control (blank hydrogel) group. Measurements utilized ALP staining and Alizarin red S assays for the in vitro study and bone dimension for the in vivo study.Hydrogel i-PRF significantly enhanced ALP activity on days 7 and 14 compared with the bone graft i-PRF and control groups (p ≀ 0.05). Similarly, calcium deposition was notably higher in the hydrogel i-PRF group on days 14 and 21. Hydrogel i-PRF also preserves the bone dimension of the rat's extraction socket compared with bone graft i-PRF. These findings highlight the superior bone regeneration capacity of the hydrogel when combined with i-PRF, attributed to enhanced osteoblast proliferation, differentiation, and mineralization mediated by PDGF and BMP bound to collagen fibrils.Hydrogel with i-PRF exhibits improved osteogenic capability compared with bone grafts, showing promise as an alternative material for periodontal regenerative applications.
A BSTRACT Introduction: The use of “Platelet-Rich Fibrin (PRF)” has gained significant attention in maxillofacial surgery for its potential to accelerate healing. This trial aims to evaluate the effectiveness of 
 A BSTRACT Introduction: The use of “Platelet-Rich Fibrin (PRF)” has gained significant attention in maxillofacial surgery for its potential to accelerate healing. This trial aims to evaluate the effectiveness of PRF in improving postoperative recovery in subjects undergoing maxillofacial surgery. Methods: In this double-blind trial, subjects were randomly assigned to either the PRF batch or the control batch. Key parameters assessed included wound healing, pain levels, soft tissue regeneration, and postoperative complications. Statistical analysis was conducted to evaluate the effectiveness of PRF using appropriate tests, with significance set at P &lt; 0.05. Results: Subjects in the PRF batch demonstrated faster wound healing ( P = 0.03) and reduced pain levels compared to the control batch. Complications such as dry socket and infection were also significantly lower in the PRF batch ( P &lt; 0.01). The analysis indicated that PRF significantly enhances tissue regeneration and reduces postoperative complications. Conclusion: Platelet-rich fibrin is effective in accelerating healing post-maxillofacial surgery, with improved clinical outcomes and lower complication rates compared to conventional treatment methods.
A BSTRACT Objective: The current study evaluated the osteogenic potential of three commercially available autogenous bone graft materials using primary human osteoblasts. Materials and Methods: Primary human osteoblasts were seeded 
 A BSTRACT Objective: The current study evaluated the osteogenic potential of three commercially available autogenous bone graft materials using primary human osteoblasts. Materials and Methods: Primary human osteoblasts were seeded onto the bone graft materials, and their adhesion, proliferation, and gene expression (Runx2 and ALP) were assessed at 4, 8, 3, and 14 days post-seeding. The materials were grouped (Group I: biphasic calcium phosphate (BCP), Group II: freeze-dried bone allografts (FDBA), Group III: deproteinized bovine bone mineral (DBBM)) and characterized for particle size and mean projection area. A two-way analysis of variance (ANOVA) with Bonferroni’s correction was used for statistical analysis. Results: Group I showed the highest osteoblast adhesion and proliferation, with the highest expression of osteogenic markers, followed by Group II and Group III. Group I had the smallest particle size. Conclusion: Deproteinized bovine bone mineral may be the most effective bone graft material for promoting osteogenesis, with implications for optimizing bone graft selection in oral surgery.
ABSTRACT Aim To assess the efficacy of topical rhEGF on healing outcomes at palatal soft‐tissue donor sites. Materials and Methods This randomised, controlled clinical trial included 60 patients who required 
 ABSTRACT Aim To assess the efficacy of topical rhEGF on healing outcomes at palatal soft‐tissue donor sites. Materials and Methods This randomised, controlled clinical trial included 60 patients who required harvesting of palatal soft‐tissue grafts. Out of two groups, the intervention group received rhEGF gel (60 ÎŒg/application for 5 days) and the comparator group received a placebo gel. Wound healing was assessed by wound area reduction and palatal early healing index (PEHI). Post‐operative pain was assessed using the numerical rating scale (NRS; 0–10), including donor site complications. Measurements were recorded daily for the first 5 days and at 2, 4 and 8 weeks post‐operatively. Results Fifty‐five participants completed the trial, with dropouts in both groups (intervention [ n = 3], control [ n = 2]). The test group showed significantly faster healing, as evidenced by higher PEHI scores ( p = 0.0011) and greater wound area reduction ( p = 0.0057). Post‐operative pain was reduced significantly in the rhEGF group, and pain was nearly absent from day 2 onwards ( p = 0.0004). No adverse effects were reported in the intervention group, whereas three participants in the control group experienced prolonged post‐operative pain. Conclusions Topical rhEGF for 5 days significantly enhanced palatal donor site healing, reduced the wound area and alleviated post‐operative pain.
Autologous Platelet Concentrates (APCs) prove to be a promising therapy in integrated health sciences, which utilizes the body’s natural healing mechanism. Derived from the patient’s own blood, APCs are rich 
 Autologous Platelet Concentrates (APCs) prove to be a promising therapy in integrated health sciences, which utilizes the body’s natural healing mechanism. Derived from the patient’s own blood, APCs are rich in growth factors,cytokines, and other proteins that facilitate tissue regeneration by reducing the inflammation and promoting healing. The utilization of APCs, particularly in regenerative medicine, orthopedics, and dermatology, has garnered increasing attention due to their potential to improve healing outcomes and reduce the risk of immune rejection. By integrating APC therapies into clinical practice, health professionals can harness the biological properties of platelets to enhance tissue repair, accelerate recovery, and optimize patient outcomes. This review explores the valuable principles behind APCs, their applications across various medical disciplines, and the potential future developments in their integration within health systems.
This study investigated the impact of increased extraplatelet content on the tissue regenerative capacity of platelet-rich plasma (PRP)-derived fibrin scaffolds. Comparative analyses were performed between a “balanced protein-concentrate plasma” (BPCP) 
 This study investigated the impact of increased extraplatelet content on the tissue regenerative capacity of platelet-rich plasma (PRP)-derived fibrin scaffolds. Comparative analyses were performed between a “balanced protein-concentrate plasma” (BPCP) and a standard PRP (sPRP), focusing on platelet and fibrinogen content, scaffold microstructure, and functional performance. Growth factor (GF) release kinetics from the scaffolds were quantified via ELISA over 10 days, while scaffold biomechanics were evaluated through rheological testing, indentation, energy dissipation, adhesion, and assessments of coagulation dynamics, biodegradation, swelling, and retraction. Microstructural analysis was conducted using scanning electron microscopy (SEM), with fiber diameter and porosity measurements. The results demonstrated that BPCP scaffolds released significantly higher amounts of GFs and total protein, especially beyond 24 h (* p &lt; 0.05). Despite a delayed coagulation process (** p &lt; 0.01), BPCP scaffolds exhibited superior structural integrity and cushioning behavior (* p &lt; 0.05). SEM revealed thicker fibers in BPCP scaffolds (**** p &lt; 0.0001), while adhesion and biodegradation remained unaffected. Notably, BPCP scaffolds showed reduced retraction after 24 h and maintained their shape stability over two weeks without significant swelling. These findings indicate that enhancing the extraplatelet content in PRP formulations can optimize fibrin scaffold performance. Further preclinical and clinical studies are warranted to evaluate the therapeutic efficacy of BPCP-derived scaffolds in regenerative medicine.
<title>Abstract</title> The repair of jaw bone defects faces dual challenges of functionality and aesthetics. The scarcity of jawbone-derived stem cells and imprecise regulation of these endogenous stem cells lead to 
 <title>Abstract</title> The repair of jaw bone defects faces dual challenges of functionality and aesthetics. The scarcity of jawbone-derived stem cells and imprecise regulation of these endogenous stem cells lead to uncertainties in osteogenic quality and speed. Constructing rational and effective biomimetic materials to regulate the dynamic balance of stem cell migration, proliferation, and differentiation represents a promising osteogenic strategy with broad prospects. Adult stem cells in different niches exhibit heterogeneity in phenotypic characteristics and lineage potential, and communication may exist between adjacent distinct stem cell populations. We hypothesize that exosomes with distinct functions secreted by osteogenic-predominant in situ stem cells may dominate the recruitment and phenotypic transition of adjacent stem cells, thereby enriching osteogenic sources, which represents a potential strategy for efficiently and stably promoting bone regeneration. This study uses bone regeneration in the maxillary posterior region (also known as the maxillary sinus area) as a research model, with PMSCs and LMSCs reported in our previous studies serving as the osteogenic-predominant in situ stem cell population and adjacent stem cell population, respectively. A "one-shell multi-core" microsphere dual sustained-release system was innovatively prepared using fibrinogen and GelMA via microemulsion combined with photocrosslinking method. This system enables sequential delivery of exosomes with distinct functions from PMSCs under conventional culture (C-exos) and osteogenesis-inductive culture (O-exos), mimicking inter-stem cell communication to promote recruitment, population expansion, and osteogenic efficiency of LMSCs. In vivo studies have shown that this system significantly enhances jawbone augmentation, achieves diversified osteogenic patterns, and provides an innovative solution for bone regeneration.
Nowadays, complication-free wound healing processes are the key to successful treatment outcomes in the context of periodontal and implant surgery, both clinically and scientifically. The main challenge here is to 
 Nowadays, complication-free wound healing processes are the key to successful treatment outcomes in the context of periodontal and implant surgery, both clinically and scientifically. The main challenge here is to achieve primary wound healing in the majority of cases. Among the scientifically documented factors that influence the healing process, it is primarily the blood supply in the surgical area and the stability of the wound achieved postoperatively that can be directly influenced by the clinician. The surgical wound closure plays a decisive role in this context in order to achieve sufficient stabilization of the wound without negatively affecting the healing process through unnecessary traumatization of the tissue or excessive tensile forces on the wound edges. It is important to bear in mind that wound healing after surgical procedures in the oral cavity does not take place under optimal conditions. A moist, microbiologically contaminated environment is present and complete immobilization of the wound is hardly possible during the early healing phases. The sutures must therefore ensure that the surgical flaps are passively secured in the intraoperatively established position, that the wound edges are in as close contact as possible - especially if grafts that initially rely on nutrition through plasmatic circulation are used - and that the wound is stabilized during the first few postoperative days. The suture material and suturing technique must be selected so that the knots do not loosen and both the suture material and soft tissue can withstand the mechanical stresses during the early wound healing phases. The search for available mechanical anchors should be the focus of interest.
Introduction The extended duration of traditional orthodontic treatment remains a significant patient concern. This study compared platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) for accelerating orthodontic tooth movement (OTM) 
 Introduction The extended duration of traditional orthodontic treatment remains a significant patient concern. This study compared platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) for accelerating orthodontic tooth movement (OTM) and assessing associated pain. Methods A total of 11 patients were studied using a split-mouth design, with randomized allocation of PRP to one quadrant and i-PRF to the contralateral quadrant. Interventions were administered at 21-day intervals. Canine retraction rates were measured using dental casts, while pain perception was quantified via visual analog scale (VAS) during a 1-week follow-up period. Results The i-PRF group demonstrated significantly faster OTM (2.13 ± 0.31 mm/month) compared to PRP (1.61 ± 0.28 mm/month; P = .0002), representing a 32.3% increase in movement rate. Pain levels were low but statistically higher with i-PRF (VAS 2.26 ± 0.98) versus PRP (VAS 1.9 ± 1.0; P = .0001), though both remained within clinically acceptable ranges. Conclusion i-PRF is more effective in accelerating OTM than PRP, with only marginally greater transient discomfort. These findings support i-PRF as a clinically viable biological adjunct for reducing orthodontic treatment duration.
This case series describes the treatment of eight cats with mesenchymal stem cell (MSC) secretome, a therapeutic modality never used before for refractory feline chronic gingivostomatitis (FCGS). The cats were 
 This case series describes the treatment of eight cats with mesenchymal stem cell (MSC) secretome, a therapeutic modality never used before for refractory feline chronic gingivostomatitis (FCGS). The cats were free of systemic illness and were not on immunomodulators during treatment. All cats received two to three treatments of MSC secretome through intramucosal injections given 3 months apart. White cell count and globulins, stomatitis disease activity index (SDAI), and histopathology were used pre- and post-treatment to assess the response to treatment. Of the eight selected cases, resolution of clinical signs and significant improvement of lesions were reported in two cats. Six cats did not have a substantial clinical response, and lesions remained mostly unchanged. Six cats had a reduction in globulins, and five cats increased in weight, respectively, after treatment. SDAI decreased in all the cats treated. The two cats that had resolution of clinical signs had the most significant decrease in serum globulins and SDAI, and both increased in weight. No adverse effects or chemistry and hematological abnormalities directly associated with the use of MSC secretome were observed in any of the cats, suggesting human-derived MSC secretome can be safely used in cats. Increases in weight and reductions in SDAI and globulinaemia were observed in a subset of cats after treatment, suggesting an immunomodulatory effect and downregulation of proinflammatory factors. Well-designed clinical trials are recommended to verify the observed effects in this study and to evaluate long-lasting clinical benefits or potential side effects of the treatment.
<ns3:p>In the anterior area of the mouth, the interdental papilla is important for dental hygiene and appearance. When it disappears, unpleasant “black triangles” form, which affects patients’ self-confidence in their 
 <ns3:p>In the anterior area of the mouth, the interdental papilla is important for dental hygiene and appearance. When it disappears, unpleasant “black triangles” form, which affects patients’ self-confidence in their smiles and makes oral hygiene more difficult. The loss of interdental papilla is caused by several variables such as tooth shape, periodontal disease, and aging. Although surgical treatments have been utilized to restore or retain missing papilla, their predictability remains unknown. In response, researchers have investigated non-invasive procedures, such as the use of fillers such as hyaluronic acid (HA). Owing to its capacity to increase tissue volume and bind water, HA, a naturally occurring polysaccharide with special rheological qualities, has become a popular choice for use as a dermal filler. It shows promise when used to cure interdental papilla loss; the effects usually last for six–12 months. This review article explores the development and history of papilla rebuilding methods, emphasizing hyaluronic acid as a cutting-edge and successful method for regaining both periodontal health and aesthetics.</ns3:p>
This case report describes an interdisciplinary approach to the aesthetic rehabilitation in a 45-year-old woman bothered by excessively long anterior teeth. Digital Smile Analysis (DSA) guided treatment planning, ensuring optimal 
 This case report describes an interdisciplinary approach to the aesthetic rehabilitation in a 45-year-old woman bothered by excessively long anterior teeth. Digital Smile Analysis (DSA) guided treatment planning, ensuring optimal proportions and soft tissue integration. Vertical Edgeless Preparation Technique (VEP) was used to establish the correct vertical position of the finishing line. Modified Coronally Advanced Tunnel (MCAT) combined with modified-Connective Tissue Grafts (Micro- and Split-CTG) was performed for root coverage and soft tissue augmentation. After uneventful healing, final ceramic restorations were seated. The integration of BOPT and MCAT optimized periodontal and prosthetic outcomes, achieving a natural, harmonious smile. This approach highlights the synergy between periodontal plastic surgery and prosthodontics in an aesthetically challenging case.
Teeth exhibiting internal root resorption or those with persistent large periapical lesions after non-surgical endodontic treatment are generally considered to have an unfavorable prognosis. Extraction of teeth with unfavorable prognosis, 
 Teeth exhibiting internal root resorption or those with persistent large periapical lesions after non-surgical endodontic treatment are generally considered to have an unfavorable prognosis. Extraction of teeth with unfavorable prognosis, followed by dental implant placement, has become an acceptable treatment option. However, dental implants are not indicated for young people with growing jaws. Consequently, it is recommended that clinicians prioritize the preservation of natural dentition in younger patients and defer implant therapy until skeletal growth has ceased. In cases where tooth preservation is attempted despite severe periradicular defects, a surgical approach is often required to manage associated symptoms. However, modern periradicular surgery frequently leads to unaesthetic complications such as conspicuous scar formation or gingival recession. The introduction of novel combinatory surgery, including guided tissue regeneration (GTR), de epithelialized free gingival graft (DFGG), and coronally advanced flap (CAF) optimizes the clinical outcomes, addressing both the functional and aesthetic needs of the patient.
Abstract In recent decades, the field of periodontology has been significantly shaped by an increasing focus on aesthetics, leading to the development of various surgical techniques to address gingival recession. 
 Abstract In recent decades, the field of periodontology has been significantly shaped by an increasing focus on aesthetics, leading to the development of various surgical techniques to address gingival recession. Miller Class I and II gingival recessions, in particular, present a persistent challenge in dental care. This case report evaluated the effectiveness of de-epithelialised autogenous free gingival grafts (DAFGGs) as a surgical intervention for improving soft-tissue in Miller Class I and II gingival recessions. The findings demonstrated that DAFGG offers notable benefits, including enhanced root coverage, increased keratinised tissue width and improved aesthetic outcomes. Furthermore, the procedure was well tolerated, causing minimal discomfort at the donor site. DAFGGs are a practical and effective treatment option for Miller Class I and II gingival recessions, offering significant clinical and aesthetic advantages.
Abstract Background: Osteoarthritis (OA) of the knee joint is a degenerative disease characterized by pain, decreased range of motion, and cartilaginous damage leading to disability. Nowadays, it is becoming more 
 Abstract Background: Osteoarthritis (OA) of the knee joint is a degenerative disease characterized by pain, decreased range of motion, and cartilaginous damage leading to disability. Nowadays, it is becoming more likely in the younger population due to sedentary and unhealthy lifestyles. Weight reduction and anti-inflammatory drugs are conservative treatment options, but newer therapies such as intra-articular injections of hyaluronic acid (HA) and platelet-rich plasma (PRP) are also being used for patients who are not responding to conservative therapies before surgical intervention. Aim and Objective: This study was designed to compare the efficacy and safety of intra-articular injections of HA and PRP in patients diagnosed with knee OA. Materials and Methods: This study included 86 patients fulfilling the inclusion and exclusion criteria, out of which 43, selected randomly, were injected with intra-articular PRP, and the others were injected with HA. Then, they were followed up at 1, 3, and 6 months, and the scores of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analog Scale (VAS) scales were used to compare the improvements compared to the baseline data at the first visit. Results: The study showed that PRP had better efficacy over HA in reducing WOMAC and VAS scores, and none of the two groups showed any adverse effects over 6 months. Conclusion: Our study demonstrates that PRP is more effective than HA, with both being safe in reducing pain and stiffness and improving physical function in OA patients.
The stability and vascular integration of a free gingival graft (FGG) are critical for achieving predictable outcomes. The success of the technique relies on precise recipient site preparation, meticulous graft 
 The stability and vascular integration of a free gingival graft (FGG) are critical for achieving predictable outcomes. The success of the technique relies on precise recipient site preparation, meticulous graft handling, and an optimized suturing protocol to ensure firm adaptation and immobilization to prevent micro-movements that could compromise healing. This case report introduces the 'Fishnet suture,' a novel microsuturing technique designed to enhance graft stabilization and provide uniform tension distribution. The approach utilizes a continuous interlocking suture with both vertical and horizontal components, creating a mesh-like pattern that anchors the graft to the periosteal bed, eliminating dead spaces, and promoting revascularization. The technique was applied in three clinical cases: a patient with multiple adjacent gingival recession defects in the anterior region of the mandible, a patient presenting peri-implant soft tissue deficiencies, and a patient with an insufficient width of keratinized tissue at an edentulous ridge. Postoperative healing was uneventful throughout, resulting in significant increase in keratinized tissue width. We interpret the favourable outcomes to be a result of effective graft stabilisation, facilitated by this novel suturing approach.
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ABSTRACT Implant dentistry and periodontology have shown an increasing demand for regenerative procedures associated with biomaterials targeting successful clinical outcomes and predictable long‐term results. Membranes applied in oral regeneration have 
 ABSTRACT Implant dentistry and periodontology have shown an increasing demand for regenerative procedures associated with biomaterials targeting successful clinical outcomes and predictable long‐term results. Membranes applied in oral regeneration have proved to be essential in regenerative procedures, increasing the quality, volume, and stability of the regenerated tissues. This review depicts and explores the past, present, and future of membranes used in periodontal and bone regeneration. Historical concepts and early studies using pioneering membranes are reviewed; physio‐chemical and biological membrane properties (e.g., wettability, roughness, biocompatibility, porosity, and mechanical characteristics) are discussed, as well as, the future directions of innovative membranes in the developing stage; and as a central focus, a summary of the clinical techniques and scientific evidence in which membrane application is significantly relevant is exposed. Today, a wide option of membranes is available on the market for clinicians to select and use in regenerative procedures according to the surgical level and desired tissue to be regenerated. For instance, non‐resorbable membranes (d‐PTFE, e‐PTFE, and Ti‐reinforced PTFE); resorbable membranes (synthetic and collagen‐based); and autologous membranes. Clinical and preclinical results in regenerative procedures using membranes such as horizontal and vertical bone augmentation, sinus lift, immediate implant placement, have shown strong positive evidence compared to spontaneous healing, meanwhile, the current use of membranes in periodontal regeneration, periimplantitis treatment, and alveolar ridge preservation has revealed reduced scientific data, suggesting the need for further investigation. Concluding, the use of membranes is predictable and relevant in oral regeneration. Nevertheless, still there is space for evolution and clinical progress in the use of membranes in oral regeneration aiming to surpass current limitations, eliminate possible contaminations, and promote faster regeneration.
Introduction: Gingival keratinization, a vital process in oral health, involves the formation of a keratin-rich protective epithelial layer, providing resilience against mechanical stress, pathogens, and environmental factors. Objective: This study 
 Introduction: Gingival keratinization, a vital process in oral health, involves the formation of a keratin-rich protective epithelial layer, providing resilience against mechanical stress, pathogens, and environmental factors. Objective: This study employs an early fusion omics approach with Least-Squares Generative Adversarial Networks (LSGAN) to generate synthetic genomic data, incorporating insights from drug interactions and geneontology annotations. Methods: Gene expression data from the NCBI GEO dataset (GSE182196) were analyzed to identify differentially expressed genes (DEGs) across diverse samples. Functional enrichment was performed using the Comparative Toxicogenomics Database (CTD) to explore chemical exposures and biological processes linked to DEGs. Outputs were standardized into TSV formats for downstream analyses. To ensure high-fidelity synthetic data generation, the LSGAN framework was optimized to minimize Mean Squared Error (MSE) and Mean Absolute Error (MAE).
Objectives: Platelet-rich plasma (PRP) and Platelet-rich fibrin matrix (PRFM) are different generations of platelet concentrates providing growth factors and cytokines aiding tissue repair. However, there is not enough research comparing 
 Objectives: Platelet-rich plasma (PRP) and Platelet-rich fibrin matrix (PRFM) are different generations of platelet concentrates providing growth factors and cytokines aiding tissue repair. However, there is not enough research comparing the efficacy of PRFM and PRP. This study aims to assess and compare the efficacy of platelet rich fibrin matrix (PRFM) with platelet-rich plasma (PRP) for the treatment of patients with non-healing leg ulcers of various etiologies. Material and Methods: A comparative, prospective, interventional, randomised, open labelled study was done recruiting a total of 64 consecutive cases of non-healing leg ulcers reporting to the department. One group received PRFM and the other received PRP dressings at 01 weekly interval for 04 sittings. Size and volume of the ulcers were calculated at baseline and weekly following each sitting. Results: In the PRP group the volume of ulcer was reduced by 60.66% after four applications, compared to 55.56% reduction in PRFM group. In the PRP group the area of ulcer was reduced by 51.85% after four applications, compared to 46.83% reduction in the PRFM group. There was a constant reduction in size after each application, in both the groups, but the difference finally had a P value &gt;0.05 which was not statistically significant. Conclusion: Both Autologous Platelet Rich Fibrin Matrix and Platelet Rich Plasma are effective modalities for treatment of leg ulcers with excellent safety profile. While PRP demonstrated superior efficacy, PRFM was also comparable, showing its potential as a viable alternative.
A smile greatly impacts perceived attractiveness and confidence. Excessive gingival display, or a “gummy smile,” often results from altered passive eruption (APE) or issues like subgingival fractures. Crown Lengthening Surgery 
 A smile greatly impacts perceived attractiveness and confidence. Excessive gingival display, or a “gummy smile,” often results from altered passive eruption (APE) or issues like subgingival fractures. Crown Lengthening Surgery (CLS), introduced by D.W. Cohen in 1962, addresses this by repositioning the gingival margin and removing soft and/or hard tissue. CLS is indicated for prosthetic, esthetic, and restorative purposes. Techniques range from traditional flaps and osseous resection to modern methods like lasers, electrocautery, piezosurgery, and CAD-CAM guided surgery. This review highlights CLS's history, indications, methods, and innovations, emphasizing its key role in dental esthetics and function. Keywords: Biologic Width, Crown Lengthening, Gingivectomy, Osseous
Background: Periodontal bone defects pose a significant challenge in stomatology, affecting dental stability and function. Objective: This study aimed to explore the clinical efficacy of concentrated growth factor (CGF) combined 
 Background: Periodontal bone defects pose a significant challenge in stomatology, affecting dental stability and function. Objective: This study aimed to explore the clinical efficacy of concentrated growth factor (CGF) combined with artificial or autologous bone powder in the treatment of periodontal bone defects. Methods: A total of 106 patients with bone defects requiring surgical intervention were divided into two groups: the control group and the observation group. Preoperative data were analyzed, and postoperative periodontal indicators, bone resorption markers, and masticatory function were assessed at baseline and 2 weeks, 1 month, 3 months, and 6 months post surgery. Results: There were no significant differences in baseline characteristics between the two groups. The observation group showed improvements in periodontal probing depth, mucosal recession, plaque index, gingival index, gingival retreat index, and bone gla protein after 6 months. The masticatory function of the observation group was significantly better at 1 to 6 months post operation, and there were significant differences in postoperative pain levels at 6 months. Conclusion: CGF combined with artificial bone powder demonstrates superior performance in masticatory function recovery and periodontal clinical parameter restoration, indicating potential benefits for periodontal bone defect treatment.
Abstract Background This case study presents the treatment of a 7 mm deep and 5 mm wide RT1 gingival recession on the mandibular left canine in a 30‐year‐old systemically and 
 Abstract Background This case study presents the treatment of a 7 mm deep and 5 mm wide RT1 gingival recession on the mandibular left canine in a 30‐year‐old systemically and periodontally healthy female, with the defect being associated with a self‐injurious habit. Methods Following counseling, self‐injurious habit cessation, and oral hygiene reinforcement, a double papilla flap (DPF) plus subepithelial connective tissue graft (SCTG) procedure (DPF+SCTG) was performed. After de‐epithelialization of the gingival margin, horizontal and vertical incisions were made, and a partial‐thickness DPF was elevated. The SCTG was placed at the cementoenamel junction level and covered by the DPF. Results Nearly complete root coverage was achieved, with recession depth reduced to 1 mm and keratinized tissue width increased from 1 mm to 6 mm. Ultrasound imaging confirmed successful graft integration and thick gingiva. At 2‐year follow‐up, creeping attachment was observed after the patient discontinued the self‐injurious habit, despite a prior recurrence that had caused additional trauma. The successful surgical outcome resulted in patient satisfaction, plaque control improvement, and prevention of further recession, benefiting the ongoing orthodontic treatment. Conclusions DPF+SCTG is an effective approach for treating an isolated deep and wide RT1 recession, providing long‐term benefits, particularly when combined with behavior modification in patients with self‐injurious habits. Key points Technique choice and patient behavior management : The combination of double papilla flap and subepithelial connective tissue graft effectively achieved significant root coverage and increased keratinized tissue width in a patient with self‐injurious habit. However, patient behavior management was crucial in preventing recurrence. Long‐term stability and creeping attachment : Despite a relapse due to the patient's habit, the thickened gingiva facilitated natural healing through creeping attachment, reinforcing the importance of both surgical intervention and behavioral modifications in maintaining long‐term stability. Ultrasound for non‐invasive monitoring : Ultrasound imaging confirmed successful graft integration and determined tissue thickness, highlighting its potential as a non‐invasive periodontal healing monitoring tool. Plain language summary Gum recession is a common condition where the gum tissue pulls away from the teeth, exposing the roots and making them more prone to damage. This report describes the treatment of a 30‐year‐old woman who had severe gum recession on her lower left canine tooth, caused by her long‐term habit of scratching the gums with her fingernail. To restore the lost tissue and protect the tooth, a double papilla flap (a surgical technique that moves nearby tissue) along with a connective tissue graft (transplanted tissue from the roof of the mouth) was used. Over 2 years, the recession was reduced by almost 90%, and the tissue over the tooth became healthier and stronger. Although her habit caused some recession to return, the thickened tissue allowed for natural healing once she controlled her habit again. This case highlights how proper surgical technique selection and execution, combined with patient behavior changes, can successfully treat severe gum recession. It also demonstrates how ultrasound imaging can be used as a non‐invasive tool to monitor soft tissue healing over time.