Biochemistry, Genetics and Molecular Biology Molecular Medicine

Hydrogels: synthesis, properties, applications

Description

This cluster of papers focuses on the properties, design, and biomedical applications of hydrogels, including their use in tissue engineering, drug delivery, and regenerative medicine. It explores stimuli-responsive polymers, scaffold design variables, and the development of polymeric gels for cell culture and tissue regeneration.

Keywords

Hydrogels; Biomedical Applications; Tissue Engineering; Stimuli-Responsive Polymers; Drug Delivery; Scaffold Design; Biomaterials; Regenerative Medicine; Polymeric Gels; Cell Culture

Abstract Aqueous solutions of poly(N-isopropyl acrylamide) show a lower critical solution temperature. The thermodynamic properties of the system have been evaluated from the phase diagram and the heat absorbed during … Abstract Aqueous solutions of poly(N-isopropyl acrylamide) show a lower critical solution temperature. The thermodynamic properties of the system have been evaluated from the phase diagram and the heat absorbed during phase separation and the phenomenon is ascribed to be primarily due to an entropy effect. From viscosity, sedimentation, and light-scattering studies of solutions close to conditions of phase separation, it appears that aggregation due to formation of nonpolar and intermolecular hydrogen bonds is important. In addition, a weakening of the ordering effect of the water-amide hydrogen bonds as the temperature is raised contributes to the stability of the two-phase system.
We present a theory of the kinetics of the swelling of a gel. The characteristic time of swelling is proportional to the square of a linear dimension of the gel … We present a theory of the kinetics of the swelling of a gel. The characteristic time of swelling is proportional to the square of a linear dimension of the gel and is also proportional to the diffusion coefficient of the gel network, which is defined as D=E/f where E is the longitudinal bulk modulus of the network, and f is the coefficient of friction between the network and the gel fluid. This constitutes an essential difference between the present theory and the previous theory which is based on the assumption that the swelling time is determined by the diffusion coefficient of the fluid molecules. Experimental data are shown for spheres of 5% polyacrylamide gels and are analyzed using the present theory. The value of the diffusion coefficient obtained from the macroscopic swelling experiments shows excellent agreement with that obtained microscopically using laser light scattering spectroscopy.
Hydrogel products constitute a group of polymeric materials, the hydrophilic structure of which renders them capable of holding large amounts of water in their three-dimensional networks. Extensive employment of these … Hydrogel products constitute a group of polymeric materials, the hydrophilic structure of which renders them capable of holding large amounts of water in their three-dimensional networks. Extensive employment of these products in a number of industrial and environmental areas of application is considered to be of prime importance. As expected, natural hydrogels were gradually replaced by synthetic types due to their higher water absorption capacity, long service life, and wide varieties of raw chemical resources. Literature on this subject was found to be expanding, especially in the scientific areas of research. However, a number of publications and technical reports dealing with hydrogel products from the engineering points of view were examined to overview technological aspects covering this growing multidisciplinary field of research. The primary objective of this article is to review the literature concerning classification of hydrogels on different bases, physical and chemical characteristics of these products, and technical feasibility of their utilization. It also involved technologies adopted for hydrogel production together with process design implications, block diagrams, and optimized conditions of the preparation process. An innovated category of recent generations of hydrogel materials was also presented in some details.
Hydrogels have become very popular due to their unique properties such as high water content, softness, flexibility and biocompatibility. Natural and synthetic hydrophilic polymers can be physically or chemically cross-linked … Hydrogels have become very popular due to their unique properties such as high water content, softness, flexibility and biocompatibility. Natural and synthetic hydrophilic polymers can be physically or chemically cross-linked in order to produce hydrogels. Their resemblance to living tissue opens up many opportunities for applications in biomedical areas. Currently, hydrogels are used for manufacturing contact lenses, hygiene products, tissue engineering scaffolds, drug delivery systems and wound dressings. This review provides an analysis of their main characteristics and biomedical applications. From Wichterle's pioneering work to the most recent hydrogel-based inventions and products on the market, it provides the reader with a detailed introduction to the topic and perspective on further potential developments.
An infinitesimal change in electric potential across a polyelectrolyte gel produces a discrete, reversible volume change. The volume of the collapsed gel can be several hundred times smaller than that … An infinitesimal change in electric potential across a polyelectrolyte gel produces a discrete, reversible volume change. The volume of the collapsed gel can be several hundred times smaller than that of the swollen gel.
Injectable hydrogels with biodegradability have in situ formability which in vitro/in vivo allows an effective and homogeneous encapsulation of drugs/cells, and convenient in vivo surgical operation in a minimally invasive … Injectable hydrogels with biodegradability have in situ formability which in vitro/in vivo allows an effective and homogeneous encapsulation of drugs/cells, and convenient in vivo surgical operation in a minimally invasive way, causing smaller scar size and less pain for patients. Therefore, they have found a variety of biomedical applications, such as drug delivery, cell encapsulation, and tissue engineering. This critical review systematically summarizes the recent progresses on biodegradable and injectable hydrogels fabricated from natural polymers (chitosan, hyaluronic acid, alginates, gelatin, heparin, chondroitin sulfate, etc.) and biodegradable synthetic polymers (polypeptides, polyesters, polyphosphazenes, etc.). The review includes the novel naturally based hydrogels with high potential for biomedical applications developed in the past five years which integrate the excellent biocompatibility of natural polymers/synthetic polypeptides with structural controllability via chemical modification. The gelation and biodegradation which are two key factors to affect the cell fate or drug delivery are highlighted. A brief outlook on the future of injectable and biodegradable hydrogels is also presented (326 references).
Hydrogels are physically or chemically cross-linked polymer networks that are able to absorb large amounts of water. They can be classified into different categories depending on various parameters including the … Hydrogels are physically or chemically cross-linked polymer networks that are able to absorb large amounts of water. They can be classified into different categories depending on various parameters including the preparation method, the charge, and the mechanical and structural characteristics. The present review aims to give an overview of hydrogels based on natural polymers and their various applications in the field of tissue engineering. In a first part, relevant parameters describing different hydrogel properties and the strategies applied to finetune these characteristics will be described. In a second part, an important class of biopolymers that possess thermosensitive properties (UCST or LCST behavior) will be discussed. Another part of the review will be devoted to the application of cryogels. Finally, the most relevant biopolymer-based hydrogel systems, the different methods of preparation, as well as an in depth overview of the applications in the field of tissue engineering will be given.
A concentrated fish soup could be gelled in the winter and re-solled upon heating. In contrast, some synthetic copolymers exhibit an inverse sol–gel transition with spontaneous physical gelation upon heating … A concentrated fish soup could be gelled in the winter and re-solled upon heating. In contrast, some synthetic copolymers exhibit an inverse sol–gel transition with spontaneous physical gelation upon heating instead of cooling. If the transition in water takes place below the body temperature and the chemicals are biocompatible and biodegradable, such gelling behavior makes the associated physical gels injectable biomaterials with unique applications in drug delivery and tissue engineering etc. Various therapeutic agents or cells can be entrapped in situ and form a depot merely by a syringe injection of their aqueous solutions at target sites with minimal invasiveness and pain. This tutorial review summarizes and comments on this soft matter, especially thermogelling poly(ethylene glycol)–(biodegradable polyester) block copolymers. The main types of injectable hydrogels are also briefly introduced, including both physical gels and chemical gels.
The polymer network of a gel, under certain conditions, undergoes a discrete transition in equilibrium volume with changes in solvent composition or temperature. This Letter demonstrates that ionization of the … The polymer network of a gel, under certain conditions, undergoes a discrete transition in equilibrium volume with changes in solvent composition or temperature. This Letter demonstrates that ionization of the gel network plays an essential role in the phase transition. The volume collapse is also observed when the $p\mathrm{H}$ within the gel is varied.
We report a strategy to create photodegradable poly(ethylene glycol)-based hydrogels through rapid polymerization of cytocompatible macromers for remote manipulation of gel properties in situ. Postgelation control of the gel properties … We report a strategy to create photodegradable poly(ethylene glycol)-based hydrogels through rapid polymerization of cytocompatible macromers for remote manipulation of gel properties in situ. Postgelation control of the gel properties was demonstrated to introduce temporal changes, creation of arbitrarily shaped features, and on-demand pendant functionality release. Channels photodegraded within a hydrogel containing encapsulated cells allow cell migration. Temporal variation of the biochemical gel composition was used to influence chondrogenic differentiation of encapsulated stem cells. Photodegradable gels that allow real-time manipulation of material properties or chemistry provide dynamic environments with the scope to answer fundamental questions about material regulation of live cell function and may affect an array of applications from design of drug delivery vehicles to tissue engineering systems.
There has been considerable progress in recent years in addressing the clinical and pharmacological limitations of hydrogels for drug delivery applications but substantial challenges remain. Here we discuss recent progress … There has been considerable progress in recent years in addressing the clinical and pharmacological limitations of hydrogels for drug delivery applications but substantial challenges remain. Here we discuss recent progress in overcoming these challenges, particularly with regards to effectively delivering hydrogels inside the body without implantation, prolonging the release kinetics of drugs from hydrogels, and expanding the nature of drugs which can be delivered using hydrogel-based approaches.
Dynamic shear oscillation measurements at small strain were used to characterize the viscoelastic properties and related differences in the molecular structure of hydrogels based on gelatin methacrylamide. Gelatin was derivatized … Dynamic shear oscillation measurements at small strain were used to characterize the viscoelastic properties and related differences in the molecular structure of hydrogels based on gelatin methacrylamide. Gelatin was derivatized with methacrylamide side groups and was subsequently cross-linked by radical polymerization via photoinitiation. The light treatment of methacrylamide gelatin solutions resulted in the production of hydrogel films with high storage modulus (G'). Mechanical spectra and thermal scanning rheology of the obtained hydrogels are described. The temperature scan of the network below and above melting point of gelatin allowed us to identify the respective contributions of chemical and physical cross-linkage to the hydrogel elastic modulus. The results indicate that the rheological properties of the gelatin-based hydrogels can be controlled by the degree of substitution, polymer concentration, initiator concentration, and UV irradiation conditions.
Nonionic N-isopropylacrylamide gel was found to undergo a discontinuous phase transition by changing a solvent composition or temperature. The observation that polymer gel with and without charge can undergo a … Nonionic N-isopropylacrylamide gel was found to undergo a discontinuous phase transition by changing a solvent composition or temperature. The observation that polymer gel with and without charge can undergo a first order volume phase transition is an evidence for the universality of the phase transition of polymer gels.
Double-network (DN) gels have drawn much attention as an innovative material having both high water content (ca. 90 wt%) and high mechanical strength and toughness. DN gels are characterized by … Double-network (DN) gels have drawn much attention as an innovative material having both high water content (ca. 90 wt%) and high mechanical strength and toughness. DN gels are characterized by a special network structure consisting of two types of polymer components with opposite physical natures: the minor component is abundantly cross-linked polyelectrolytes (rigid skeleton) and the major component comprises of poorly cross-linked neutral polymers (ductile substance). The former and the latter components are referred to as the first network and the second network, respectively, since the synthesis should be done in this order to realize high mechanical strength. For DN gels synthesized under suitable conditions (choice of polymers, feed compositions, atmosphere for reaction, etc.), they possess hardness (elastic modulus of 0.1–1.0 MPa), strength (failure tensile nominal stress 1–10 MPa, strain 1000–2000%; failure compressive nominal stress 20–60 MPa, strain 90–95%), and toughness (tearing fracture energy of 100∼1000 J m−2). These excellent mechanical performances are comparable to that of rubbers and soft load-bearing bio-tissues. The mechanical behaviors of DN gels are inconsistent with general mechanisms that enhance the toughness of soft polymeric materials. Thus, DN gels present an interesting and challenging problem in polymer mechanics. Extensive experimental and theoretical studies have shown that the toughening of DN gel is based on a local yielding mechanism, which has some common features with other brittle and ductile nano-composite materials, such as bones and dentins.
Very strong hydrogels (with a fracture strength of some tens of MPa) , as required for both industrial and biomedical applications, have been generated by inducing a double‐network (DN) structure … Very strong hydrogels (with a fracture strength of some tens of MPa) , as required for both industrial and biomedical applications, have been generated by inducing a double‐network (DN) structure for various combinations of hydrophilic polymers. The Figure shows a hydrogel before, during, and after application of a fracture stress of 17.2 MPa.
Abstract Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range … Abstract Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems' intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.
Novel nanocomposite hydrogels (NC gels) with a unique organic–inorganic (clay) network structure (see Figure) have been synthesized by in-situ free radical polymerization. The resulting NC gels exhibit high structural homogeneity, … Novel nanocomposite hydrogels (NC gels) with a unique organic–inorganic (clay) network structure (see Figure) have been synthesized by in-situ free radical polymerization. The resulting NC gels exhibit high structural homogeneity, superior elongation with near-complete recovery, good swellability, and rapid de-swelling in response to temperature changes.
Polymers that can respond to external stimuli are of great interest in medicine, especially as controlled drug release vehicles. In this critical review, we consider the types of stimulus response … Polymers that can respond to external stimuli are of great interest in medicine, especially as controlled drug release vehicles. In this critical review, we consider the types of stimulus response used in therapeutic applications and the main classes of responsive materials developed to date. Particular emphasis is placed on the wide-ranging possibilities for the biomedical use of these polymers, ranging from drug delivery systems and cell adhesion mediators to controllers of enzyme function and gene expression (134 references).
Nanogels are swollen nanosized networks composed of hydrophilic or amphiphilic polymer chains. They are developed as carriers for the transport of drugs, and can be designed to spontaneously incorporate biologically … Nanogels are swollen nanosized networks composed of hydrophilic or amphiphilic polymer chains. They are developed as carriers for the transport of drugs, and can be designed to spontaneously incorporate biologically active molecules through formation of salt bonds, hydrogen bonds, or hydrophobic interactions. Polyelectrolyte nanogels can readily incorporate oppositely charged low-molecular-mass drugs and biomacromolecules such as oligo- and polynucleotides (siRNA, DNA) as well as proteins. The guest molecules interact electrostatically with the ionic polymer chains of the gel and become bound within the finite nanogel. Multiple chemical functionalities can be employed in the nanogels to introduce imaging labels and to allow targeted drug delivery. The latter can be achieved, for example, with degradable or cleavable cross-links. Recent studies suggest that nanogels have a very promising future in biomedical applications.
This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to … This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Recently, bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. This article addresses various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding.
Uncontrolled arterial bleeding and wound infection following severe trauma pose significant challenges to existing tissue adhesives. This study developed an injectable hydrogel based on ε-polylysine, carboxymethyl chitosan, and oxidized dextran … Uncontrolled arterial bleeding and wound infection following severe trauma pose significant challenges to existing tissue adhesives. This study developed an injectable hydrogel based on ε-polylysine, carboxymethyl chitosan, and oxidized dextran (DECG) to address the deficiencies of current materials. This hydrogel not only possesses rapid and strong adhesion and self-healing properties by incorporating basic fibroblast growth factor (bFGF) but also demonstrates excellent porosity (30 μm), biocompatibility, antioxidant properties, and antibacterial performance. Additionally, the adhesive strength of the hydrogel reached 0.627 MPa, capable of withstanding pressures of 657.6 ± 18.71 mmHg. The hydrogel transitions from a liquid to a solid state within just 10 s. More importantly, this study used the rat abdominal aorta as an in vivo hemostasis model, clearly confirming that the DECG hydrogel can effectively prevent fatal noncompressible hemorrhage in the rat abdominal aorta injury model. Further investigations revealed that the DECG hydrogel also promoted the high expression of COL-1, CD31, VEGF, α-SMA, and PCNA, improving arterial wound healing and reducing the occurrence of aneurysms. Overall, the meticulously developed DECG hydrogel in this study demonstrates outstanding performance, precisely meeting the urgent demands of clinical applications and showing promising clinical prospects in controlling difficult bleeding situations and promoting the healing of challenging infectious wounds.
ABSTRACT With the increasing demand for medical and health products, their impact on the environment and health has become increasingly prominent. Natural superabsorbent polymer (SAP), known for its excellent water … ABSTRACT With the increasing demand for medical and health products, their impact on the environment and health has become increasingly prominent. Natural superabsorbent polymer (SAP), known for its excellent water absorption, biodegradability, and eco‐friendly properties, demonstrates broad application prospects in the medical and hygiene sectors. This article reviews the classification, synthesis methods, and applications of natural SAP in wound dressings, hygiene products, and drug delivery systems, with a focus on the antibacterial performance and mechanisms of its composites with inorganic, organic, and natural antimicrobial agents. It also summarizes research progress on the biodegradability of natural SAP and outlines future directions, including the development of multifunctional and intelligent SAP, enhanced biosafety assessments, and exploration of applications in emerging fields, highlighting their significant role in promoting sustainable development.
ABSTRACT Aerogels are highly valued for meat preservation; however, their mechanical properties are compromised by structural changes upon water absorption, which limits their potential applications. In this study, β‐cyclodextrin (β‐CD) … ABSTRACT Aerogels are highly valued for meat preservation; however, their mechanical properties are compromised by structural changes upon water absorption, which limits their potential applications. In this study, β‐cyclodextrin (β‐CD) was used as a carrier to encapsulate oregano essential oil (OEO), forming microcapsules (OEO/CD) that were incorporated into gelatin‐polyvinyl alcohol (Gel‐PVA) superabsorbent aerogels (Gen@Gel‐PVA). Additionally, the mechanical strength and absorbency of gelatin were improved through crosslinking with genipin (Gen). The aerogels were then applied to beef preservation to evaluate their effectiveness in maintaining freshness. Results showed that Gel‐PVA aerogels crosslinked with Gen displayed significantly enhanced properties, including a 28% increase in porosity, a 384% improvement in mechanical strength and a 57% increase in water absorption. Furthermore, the aerogels exhibited excellent antibacterial performance, as the OEO/CD‐Gen@Gel‐PVA aerogels extended the shelf life of fresh beef from 4 to 8 days at 4 °C by effectively inhibiting microbial growth, protein oxidation and lipid oxidation. The aerogels prepared in this study show considerable potential for fresh meat preservation.
Chronic wounds, such as diabetic ulcers and pressure injuries, remain a major global health burden, affecting over 40 million people worldwide and imposing significant socioeconomic strain. Hydrogel-based wound dressings have … Chronic wounds, such as diabetic ulcers and pressure injuries, remain a major global health burden, affecting over 40 million people worldwide and imposing significant socioeconomic strain. Hydrogel-based wound dressings have gained clinical attention for their ability to maintain moisture, mimic the extracellular matrix, and support tissue regeneration. However, traditional hydrogels often lack the mechanical robustness, antimicrobial efficacy, and dynamic responsiveness needed to treat complex wound environments effectively. To address these limitations, nanohybrid hydrogels, composite systems that integrate functional nanomaterials into hydrogel matrices, have emerged as intelligent platforms for advanced wound care. These systems enable multifunctional therapeutic action, including antibacterial activity, antioxidant regulation, angiogenesis promotion, immune modulation, and stimuli-responsive drug delivery. This review synthesizes recent advances in nanohybrid hydrogel design, beginning with an overview of traditional polymeric systems and their constraints. We categorize functional mechanisms according to biological targets and classify nanohybrid architectures by material type, including metal-based nanoparticles, nanozymes, carbon-based nanomaterials, polymeric nanogels, and metal–organic frameworks. Representative studies are summarized in a comparative table, and challenges related to biosafety, clinical translation, and design optimization are discussed. Nanohybrid hydrogels represent a rapidly evolving frontier in wound care, offering bioresponsive, multifunctional platforms with the potential to transform chronic wound management.
Abstract Network imperfections, such as multi‐dispersed junctions and dangling chains, significantly impair the mechanical performance of hydrogels and elastomers synthesized via free radical reactions (FRRs). Great efforts have been made … Abstract Network imperfections, such as multi‐dispersed junctions and dangling chains, significantly impair the mechanical performance of hydrogels and elastomers synthesized via free radical reactions (FRRs). Great efforts have been made to introduce sacrificial structures to enhance toughness but cause pronounced hysteresis, leaving a comprehensive solution elusive. Herein, a class of robust single‐network hydrogels with minimal imperfections is reported by employing nano‐crosslinkers and nano‐initiators to produce monodispersed crosslinking points and eliminate dangling‐chain defects, in the formation of dual crosslinking of thiolate‐Au bond and chemically covalent bond in the network. As a result, the hydrogel achieves a maximum fracture toughness (78 500 J m −2 ) and fatigue resistance (2480 J m −2 ), with over 13 and 55 fold increases attributed to the incorporation of dangling chains and dual crosslinking, respectively, without compromising its low hysteresis (0.07). Eliminating dangling chains also improves interfacial contact and osmotic pressure resistance, enabling exceptional underwater self‐healing and swelling properties. Even with a high water‐uptake of up to 95 wt.%, the swollen hydrogel exhibits stretchability exceeding 2000%, without obvious mechanical degradation after one month of water incubation. This work demonstrates a model system for developing resilient polymers with minimized imperfections derived from FRRs, showing numerous potential applications in underwater applications.
This laboratory study was conducted during October, 2023 to December, 2023 at Indian Agricultural Research Institute, New Delhi and focused on the synthesis, characterization, and evaluation of poly (acrylic acid)-co-acrylamide … This laboratory study was conducted during October, 2023 to December, 2023 at Indian Agricultural Research Institute, New Delhi and focused on the synthesis, characterization, and evaluation of poly (acrylic acid)-co-acrylamide / bentonite based nanoclay-polymer composites (NCPCs) for their potential application as slow-release nitrogen fertilizers. NCPCs were synthesized by co-polymerization reaction between partially neutralized aqueous acrylic acid solution with acrylamide and bentonite clay (in varied amount; 8, 12 and 16% by weight of acrylic acid), in presence of crosslinker and free radical reaction initiator. The composites were characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) techniques for physical properties. The water absorption and retention studies revealed high swelling capacities of the NCPCs, enabling gradual water and nitrogen release. Nitrogen release studies revealed that NCPCs loaded with urea ammonium nitrate (UAN) in soil showed a slower (40–60% less total N release over 28 days) and more sustained release compared to conventional UAN fertilizer. NCPCs regulated nitrogen availability by releasing ammonium (NH4+) and NO3 at a slower rate during the incubation period, but the effect was more visible upto 15 days. Further N release from UAN-loaded studied using zero-order, first-order and Higuchi’s kinetic reaction model; results highlighted that N release rate followed first-order kinetic reaction evident from higher R2 (0.93) over others. In conclusion, NCPCs can sustain N availability from UAN in soil for longer duration and offers its suitability for agricultural application for better nutrient use efficiency over conventional UAN fertilizer.
Abstract Conventional hydrogel preparation typically involves the use of solvents (mostly water), which increases the free volume between polymer chains and weakens their interactions, resulting in mechanically weak hydrogels with … Abstract Conventional hydrogel preparation typically involves the use of solvents (mostly water), which increases the free volume between polymer chains and weakens their interactions, resulting in mechanically weak hydrogels with limited viscoelasticity. Here, a solvent‐free synthesis strategy is presented to produce tough, swelling‐resistant physical hydrogels with ultra‐wide frequency viscoelasticity (loss factor tan δ > 0.3 at 10 −10 –10 5 Hz). This is achieved through the bulk copolymerization of highly miscible hydrophilic and hydrophobic monomers, forming water‐free copolymers that develop into phase‐separated hydrogels with dense chain entanglements upon equilibration in water. The resulting hydrogel exhibits significant mechanical enhancements over counterparts prepared through classical micellar copolymerization, with stiffness, strength, and fracture toughness increased by up to 81, 46, and 41 times, respectively. As a proof‐of‐concept demonstration, the tough hydrogel with excellent swelling resistance is applied as a sound‐absorbing coating for underwater vehicles, minimizing acoustic interference during marine research through its strong viscoelasticity and near‐perfect acoustic impedance matching with water. Unlike conventional solvent‐assisted polymerization methods used for hydrogel preparation, bulk copolymerization offers advantages such as ultra‐high monomer concentration, pure products, and straightforward process, providing new insights for developing simple yet tough hydrogels that are not only promising for underwater applications but also conducive to theoretical studies.
Abstract Anisotropic hydrogels are promising candidates as load‐bearing materials for tissue engineering, while huge challenges remain in exploring effective and scalable methods for the preparation of anisotropic hydrogels with simultaneous … Abstract Anisotropic hydrogels are promising candidates as load‐bearing materials for tissue engineering, while huge challenges remain in exploring effective and scalable methods for the preparation of anisotropic hydrogels with simultaneous high tensile strength, large toughness, good fracture strain, excellent fatigue and swelling resistances. Inspired by the brick‐and‐mortar layered structure of nacre and the hierarchical fibril strucure of soft tissues (e.g., tendon and ligament), a facile organogel‐assissted calendering strategy is reported to design anisotropic hydrogels with a highly oriented and dense fiber lamellar strucure. The synergy of shearing and annealing promotes macromolecular chain alignment and crystallinity along the calendering direction while forming a nacre‐like lamellar morphology in the thickness direction. The tensile strength, elastic modulus, toughness and fracture energy of the anisotropic hydrogels can reach as high as 41.0 ± 6.4 MPa, 67.0 ± 5.1 MPa, 46.2 ± 3.3 MJ m −3 , and 62.20 ± 8.55 kJ m −2 , respectively. More importantly, the hydrogels show excellent crack growth and swelling resistances with the fatigue threshold increased to 2170 J m −2 . This study provides a promising approach for fabrication of large‐sized biomimetic anisotropic hydrogels with outstanding mechanical properties for biomedical and engineering applications.
ABSTRACT Hydrogels can be combined with molecular carriers to achieve controlled delivery of hydrophobic drugs. The purpose of this study was to use an experimental protocol consisting of spatially localized … ABSTRACT Hydrogels can be combined with molecular carriers to achieve controlled delivery of hydrophobic drugs. The purpose of this study was to use an experimental protocol consisting of spatially localized magnetic resonance (MR) techniques to investigate the changes in a poly(N‐isopropylacrylamide) P(NIPAM) hydrogel incorporating ‐cyclodextrins (CD) undergoing a volume phase transition (VPT). The MR protocol presented in this study allows to follow the shrinking of the hydrogel and the release of CD, with subsequent determination of the self‐diffusion coefficients of both water and CD in the hydrogel. The obtained data enable a detailed correlation of the change in hydrogel structure and spatial variation in gel volume and the corresponding time‐dependent spatial variation in the concentration of CD.
ABSTRACT Self‐healing zwitterionic hydrogels (ZIHs) have sparked widespread attention because of their intriguing properties and potential applications. One of the key features of ZIHs is their inherent antifouling properties, making … ABSTRACT Self‐healing zwitterionic hydrogels (ZIHs) have sparked widespread attention because of their intriguing properties and potential applications. One of the key features of ZIHs is their inherent antifouling properties, making them appealing for various biomedical applications. A notable characteristic of ZIHs is their self‐healing capability, enabling them to mend damage and restore their mechanical properties, hence prolonging their lifespans and enhancing their functionality. Self‐healing ZIHs exhibit excellent properties as wound‐dressing materials by creating a moist environment that promotes the healing process. In addition to their antifouling, self‐healing, wound‐healing, and wound‐dressing applications, zwitterionic self‐healing hydrogels have shown promise in cardiac tissue engineering and cell encapsulation. In cell encapsulation, ZIHs provide promising platforms for the encapsulation and delivery of numerous cell types, including stem cells and therapeutic cells, as well as enable controlled release and protection during transplantation. The self‐healing feature of ZIHs provides long‐term stability and durability of these materials. This review focuses on state‐of‐the‐art advancements in the synthesis strategies, self‐healing mechanisms, and applications of ZIHs, offering an integrated perspective not previously addressed in the literature.
ABSTRACT In the drug delivery systems and biomedical fields, pH‐sensitive hydrogels have found potential applications. In this research study, a novel hydrogel of chitosan/poly (vinyl alcohol), cross‐linked with tetraethoxyorthosilane, is … ABSTRACT In the drug delivery systems and biomedical fields, pH‐sensitive hydrogels have found potential applications. In this research study, a novel hydrogel of chitosan/poly (vinyl alcohol), cross‐linked with tetraethoxyorthosilane, is synthesized for drug delivery by a solution casting method. Graphene oxide (GO) and iron sulfide (FeS 2 ) nanoparticles were incorporated into hydrogels to enhance their swelling properties in external media, which made them fascinating in drug delivery applications. FeS 2 nanoparticles were synthesized by the solid‐state method and characterized by x‐ray diffraction (XRD). The crystallinity of synthesized nanocomposite hydrogels and the dispersion of nanoparticles into the matrix of hydrogels were characterized by the XRD technique. In the nanocomposite hydrogel, the existence of integrated constituents and crosslinking was interpreted by FT‐IR. The surface morphology of hydrogels was exhibited by SEM. The swelling characteristics of hydrogel were examined by studying their behavior in distinct phases, such as aqueous, pH, and electrolyte solutions. The maximum swelling of 0.20 g/g, 0.19 g/g, and 0.07 g/g was observed in CS/PVA/GO + FeS 2 (TA‐3), CS/PVA/GO (TA‐1), and CS/PVA/FeS 2 (TA‐2) hydrogel, respectively. The most suitable hydrogel with high swelling performance was loaded with a model drug. Cefadroxil monohydrate (CMO), an antibacterial drug, was selected as a model drug for loading. In vitro drug release behavior was studied in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The release profile of the cefadroxil monohydrate drug was investigated by using a UV spectrophotometer at 264 nm. The release profile exhibited 1.2% release in SGF (pH 1.2) and 92.15% controlled release in SIF (pH 6.8). These results indicate that the synthesized nanocomposite hydrogels hold the potential as promising antibacterial drug delivery systems.
Advances in the development of lipid nanoparticles have resulted in delivery systems that both protect the encapsulated drug and improve therapeutic outcomes. When introduced in vivo, nanoparticles are rapidly covered … Advances in the development of lipid nanoparticles have resulted in delivery systems that both protect the encapsulated drug and improve therapeutic outcomes. When introduced in vivo, nanoparticles are rapidly covered by a biomolecular corona, influencing their biological fate, i.e., interaction with cells, uptake, and intracellular fate. This study explores the interactions between nonlamellar lipidic drug delivery systems and non-lipolytic components of complex cell culture media, focusing on the dynamic formation of the corona and its effects on the lipid nanoparticle behavior. Monoglyceride formulations were monitored for changes in nanostructure and particle size, and mechanisms for these changes were elucidated. Not only do these biomacromolecules influence the size and structure of the nanoparticles themselves, but they can simultaneously diffuse into the mesophase nanostructure. The study highlights that lipid nanoparticles undergo dynamic changes in physiological conditions influenced by adsorbed proteins and other nondegradative components in complex cell culture media, separate from effects caused by lipases or other enzymatic factors. These induced structural transformations can significantly alter the nanoparticles' physical properties and drug release profiles, potentially causing deviation from their intended therapeutic performance. Understanding these interactions is thus crucial for optimizing the design and functionality of lipid-based drug delivery systems in biomedical applications.
Abstract Hydrogels, with their unique properties between fluid and solid states, have attracted significant attention due to their unique constitutive relationships and extensive applications. However, the mechanical behavior of hydrogels … Abstract Hydrogels, with their unique properties between fluid and solid states, have attracted significant attention due to their unique constitutive relationships and extensive applications. However, the mechanical behavior of hydrogels becomes highly nonlinear with various enhancement strategies, making it challenging to understand the changes in their constitutive equations and polymer chain conformations. It is one of the difficult problems to solve the previously neglected crowding effect in hydrogel elasticity. To address this, based on extended Flory-Fisk thermodynamics and freely jointed chain model, a constitutive model is established to elucidate the conformational transformations and variations in end-to-end distances of chains within solution environments. The model considers the effects of excluded volume, swelling, solute-solvent interactions, and external loads on conformational equilibrium and interaction energies. The free energy model was validated through comparative analysis with experimental data from the literature. The results show that the proposed model can accurately predict the mechanical behavior of hydrogels under different conditions, providing a deeper understanding of their conformational changes and mechanical properties.
Abstract Hydrogels are essential biomaterials for biomedical applications, valued for their tunable properties and biocompatibility. A key feature influencing their function is porosity, which governs transport properties. Cryogenic scanning electron … Abstract Hydrogels are essential biomaterials for biomedical applications, valued for their tunable properties and biocompatibility. A key feature influencing their function is porosity, which governs transport properties. Cryogenic scanning electron microscopy (cryo‐SEM) is widely used to directly characterize porosity, but may introduce structural artifacts. Accurately characterizing the porosity of a hydrogel in its native state remains a challenge. Here, we characterized the hydrogel porosity in its native state using particle tracking assay and compared the results with cryo‐SEM in polyethylene glycol (PEG) hydrogels. Both methods revealed the presence of micropores in PEG, likely arising from defects during polymerization. The equilibrium swelling assay showed nanoscale mesh sizes between polymer chains, distinct from the micron‐scale pores. To overcome conventional limitations, we developed a novel three‐dimensional (3D) pore reconstruction approach by leveraging the convex hull algorithm. The method enabled measurement of pore volume, surface area, sphericity, and size distribution. We found that cryo‐SEM underestimates pore diameters due to the two‐dimensional (2D) depiction, but after the 2D‐to‐3D conversion, remarkably similar pore dimensions are obtained. By advancing porosity analysis, this work provides insights for tailoring hydrogels to optimize interactions with cells, biomolecules, and therapeutic agents, opening avenues in drug delivery, tissue engineering, and other biomedical applications.
Oral antidiabetic drugs remain the primary therapeutic strategy for type 2 diabetes mellitus (T2DM) due to its convenience, cost-effectiveness, and non-invasive, while achieving glycemic control in >60% of patients. However, … Oral antidiabetic drugs remain the primary therapeutic strategy for type 2 diabetes mellitus (T2DM) due to its convenience, cost-effectiveness, and non-invasive, while achieving glycemic control in >60% of patients. However, compromised bioavailability of oral antidiabetic drugs frequently leads to drug-induced hypoglycemia (sulfonylureas like glibenclamide), posing significant clinical risks. To address this issue, microstirring oral pills are designed but various challenges remain, including uncontrollable release and low biocompatibility. Here, inspired by the morphology and helical motion of Phacus helicoides, millimeter-sized spheres with an inner helical structure are designed. Owing to their inner spiral structure, helical spheres (HSs) can simultaneously self-rotate and move circularly, giving them excellent and controllable mixing capacity via an external magnetic field. Moreover, HSs can imitate metabolic processes, including the adsorption, catalysis, and release capacity of Phacus helicoides, which can effectively reduce postprandial blood glucose levels (<2 h) in rats with type 2 diabetes. Additionally, these novel microstirring oral spheres with inner helical structure can reduce the incidence of hypoglycemia (14.2-18.6%) of the traditional sulfanilamide drug (glibenclamide) to 3.8%. Thus, it is anticipated that HSs have a potential for drug delivery as microstrring oral pills to improve bioavailability and avoid the drug-induced hypoglycemia of T2DM patients.
Rapid volumetric rewarming methods are needed to enable the effective cryopreservation and recovery of large volumes of biological cells for therapy and banking of tissues and organs. Ultrasonic rewarming is … Rapid volumetric rewarming methods are needed to enable the effective cryopreservation and recovery of large volumes of biological cells for therapy and banking of tissues and organs. Ultrasonic rewarming is currently under development, but its effect on cells and their post-rewarming viability has not yet been established. Here, we compare ultrasonic rewarming with the gold-standard 37°C water bath using cryovials containing cryopreserved alginate encapsulated liver spheroids. Mean rewarming rates are used to establish the exposure time to rewarm to 5°C for higher power (100 W) and lower power (20 W) ultrasonic rewarming. These electrical powers correspond to free-field pressures along the central cryovial axis of 2.8 MPa and 1.3 MPa, respectively. Ultrasonic rewarming is faster than the gold-standard (120±5 s), taking 88 s (36% faster) and 34s (350% faster) to rewarm to 5°C with the lower and higher powers. We measure post-rewarming liver spheroid viability and viable cell number across the 96-hour recovery period. The lower power improves viability by 1% and the higher power reduces viability by 2% on average, relative to the gold-standard. There were no significant differences in viable cell number between rewarming methods. Our findings will serve as a foundation for ultrasonic cryovial rewarming and demonstrates potential for scaling to larger volumes.
Hydrogels are three-dimensional network structures formed by hydrophilic polymer chains through chemical or physical cross-linking [...]. Hydrogels are three-dimensional network structures formed by hydrophilic polymer chains through chemical or physical cross-linking [...].
Gels with simultaneously high strength, large strain, great toughness, intrinsic self-healing capability, and recyclability are highly attractive for industrial development and applications. However, their preparation remains a significant challenge owing … Gels with simultaneously high strength, large strain, great toughness, intrinsic self-healing capability, and recyclability are highly attractive for industrial development and applications. However, their preparation remains a significant challenge owing to mutually exclusive mechanisms, let alone achieving such properties within a brief period via a facile method. In this study, a one-step "frozen salting-out" strategy is proposed to rapidly prepare poly(vinyl alcohol) (PVA) gels with outstanding mechanical properties through the construction of a robust polymer network. The gel exhibits a fracture strain of 1350%, an extremely high tensile stress of 31.1 MPa, and exceptional toughness of 247.7 MJ·m-3. The damaged gel can heal in a manner similar to that of welding and can be recycled to restore its excellent mechanical properties. Furthermore, the stress of the gel can reach 117.0 MPa through a prestretching process that optimizes the polymer network. The entire preparation process is highly convenient. Time is of the essence, and the transformation from solution to robust gel requires approximately 1 h. This study provides a facile and effective strategy for preparing superstrong and tough gels.
While carboxymethyl cellulose (CMC)—a biocompatible and water-soluble cellulose derivative—holds promise for biomedical applications, challenges remain in synthesizing CMC-based hydrogels with covalent crosslinking through free radical polymerization without requiring complex, multi-step … While carboxymethyl cellulose (CMC)—a biocompatible and water-soluble cellulose derivative—holds promise for biomedical applications, challenges remain in synthesizing CMC-based hydrogels with covalent crosslinking through free radical polymerization without requiring complex, multi-step processes. In this study, we introduce a facile one-pot strategy that combines CMC with acrylamide (AAm) under cryogelation and low-intensity UV irradiation to achieve covalent bonding and a high polymerization yield. The resulting polyacrylamide/carboxymethyl cellulose (PAAm/CMC) porous gels were systematically evaluated for their chemical, physical, thermal, and drug-release properties, with a focus on the effects of AAm concentration and polymerization temperature (frozen vs. room temperature). Notably, the cryogel synthesized with 2.5 M AAm (PC2.5) exhibited significantly enhanced mechanical properties—that is, an 8.4-fold increase in tensile modulus and a 26-fold increase in toughness—compared with the non-cryo gel. Moreover, PC2.5 demonstrated excellent cyclic compression stability in water and phosphate-buffered saline (PBS), with less than 10% reduction in modulus after 100 cycles. These increases in the mechanical properties of PC2.5 are attributed to the formation of macropores with high polymer density and high crosslinking density at the pore walls. PC2.5 also showed slower drug release in PBS and good cytocompatibility. This study presents a simplified and efficient route for fabricating mechanically robust, covalently crosslinked PAAm/CMC cryogels, highlighting their strong potential for biomedical applications in drug delivery systems.
Purpose The mechanical environment of the extracellular matrix strongly influences how cells behave — affecting their adhesion, migration, growth, and differentiation. While stiffness has been widely studied, recent research highlights … Purpose The mechanical environment of the extracellular matrix strongly influences how cells behave — affecting their adhesion, migration, growth, and differentiation. While stiffness has been widely studied, recent research highlights the importance of viscoelasticity, especially the stress relaxation timescale, in how cells sense and respond to their surroundings. According to the widely accepted motor–clutch model, optimal cell spreading occurs when the stress relaxation timescale is similar to the timescale of molecular clutch binding. Polyacrylamide (PAAm) hydrogels, due to their tunable mechanical properties and bioinert nature, are commonly used as model substrates in mechanobiology. In this study, we investigated how changing the concentrations of crosslinker (N,N′-methylenebisacrylamide) and initiator (ammonium persulfate) affects the viscoelastic behavior of PAAm hydrogels. Methods Using creep–recovery tests and fitting the data to the Standard Linear Solid model, we extracted mechanical parameters and calculated the stress relaxation timescale. Results We found that the relaxation timescale increases with crosslinker concentration up to 0.05%, then decreases — suggesting an optimal crosslinking density. At a fixed 0.05% crosslinker, increasing initiator concentration reduced the relaxation timescale, likely due to faster gelation and less organized network formation. Conclusions These findings demonstrate how simple adjustments in polymerization parameters can tune hydrogel relaxation behavior for mechanobiological applications.
The oral mucosa plays a critical role in protecting the body from external threats and serves as a key site for drug absorption. However, ethical concerns and the high costs … The oral mucosa plays a critical role in protecting the body from external threats and serves as a key site for drug absorption. However, ethical concerns and the high costs associated with animal models traditionally used for oral mucosa research have increased the demand for reliable alternatives. In this study, we developed two types of protein-based double-network hydrogels to replicate the mechanical and structural properties of buccal mucosa and hard palate, respectively. By incorporating polyprotein into the rigid network and elastin-like peptides as the loose network, we fabricated hydrogels that closely resemble the physical properties of natural oral mucosa. These hydrogels exhibit a microporous structure, as well as surface and mechanical properties, and particle permeability comparable to native tissue, while maintaining excellent biocompatibility. We anticipate that these hydrogels can serve as model systems for investigating drug delivery, pathogen interactions, and aerosol particle adsorption in the oral mucosa. The design principles presented in this study could also be extended to fabricate protein-based biomaterials that mimic mucosal tissues in the respiratory, gastrointestinal, and urogenital tracts, providing a general approach for developing biomimetic materials for mucosal tissues.
Abstract Hydrogels are widely studied for their stimuli‐responsive properties. They adapt to external stimuli, including physical, chemical and biological ones. To enhance adaptability in complex environments, multi‐responsive hydrogels have been … Abstract Hydrogels are widely studied for their stimuli‐responsive properties. They adapt to external stimuli, including physical, chemical and biological ones. To enhance adaptability in complex environments, multi‐responsive hydrogels have been developed, which either react to multiple stimuli independently or cooperatively (multistimuli‐response) or exhibit multiple responses triggered by single or multiple stimuli (multi‐response). Their properties depend on polymer type, molecular weight, cross‐linking, and water content, which affect mechanical behavior and response. To address their inherent fragility, polymer‐inorganic nanocomposite hydrogels integrate the advantages of both components, yielding enhanced functionalities. Among various nanofillers, smectites have been extensively studied for improving mechanical strength and responsiveness. Polymer‐smectite nanocomposite hydrogels exhibit enhanced elasticity, toughness, thermal stability, gas barrier properties, and responsiveness to external stimuli, expanding their applications in biomedical engineering, environmental remediation, and smart materials. This review discusses the fundamentals of polymer‐smectite nanocomposite hydrogels, their design strategies, and the role of smectite in enabling multi‐responsive behavior. The classification based on the site of responsiveness (polymer network and smectite) is presented, highlighting the important role of smectite in controlling the response and potential applications. Finally, challenges are addressed, emphasizing smectite's role in advancing next‐generation smart materials.
Abstract Injectable hydrogels with shear-thinning and self-healing properties are critical for biomedical applications including 3D bioprinting and regenerative medicine. While granular hydrogels inherently exhibit these properties, they often lack post-injection … Abstract Injectable hydrogels with shear-thinning and self-healing properties are critical for biomedical applications including 3D bioprinting and regenerative medicine. While granular hydrogels inherently exhibit these properties, they often lack post-injection stability. Here, we developed an electrostatically stabilized granular hydrogel system composed of norbornene-modified hyaluronic acid (NorHA) microgels and cationic gelatin ((+) Gel). NorHA microgels (9.91 ± 4.85 μm diameter) were synthesized via batch emulsification, while (+) Gel was prepared by modifying gelatin with ethylene diamine to increase zeta potential from 2.08 ± 0.97 mV to 13.76 ± 1.11 mV. The negatively charged NorHA microgels formed stable materials when combined with (+) Gel through electrostatic interactions, confirmed by gel inversion tests and salt sensitivity studies. Rheological characterization revealed that (+) Gel addition produced poroelastic behavior and strain-stiffening properties, with storage modulus and yield onset increasing under compression. Large amplitude oscillatory shear analysis showed strain-stiffening behavior (e3 &gt; 0) that enhanced with both (+) Gel concentration and compression. Confocal microscopy demonstrated tunable porosity through gelatin fraction control, with (+) Gel forming aggregate-like clusters. Extrusion testing showed formulations required low injection pressures (0.47-0.91 kPa) comparable to PBS and significantly lower than Pluronic, while forming robust filaments up to 23 mm in length. The materials exhibited rapid self-healing behavior and maintained structural integrity post-extrusion. This electrostatically stabilized granular hydrogel system offers a promising platform for injectable biomaterials that combine ease of delivery with post-injection stability for wound healing and 3D bioprinting applications.