Hydrogel Biomaterials Research Articles

Hydrogel Dressing Biomaterial Enriched with Vitamin C: Synthesis and Characterization

Materials engineering has become an important tool in the field of hydrogel dressings used to treat difficult-to-heal wounds. Hydrogels filled with bioactive substances used as a targeted healing system are worthy of attention. Vitamin C has healing and supporting effects in the treatment of many skin problems. The aim of the research was to produce a hydrogel biomaterial enriched with ascorbic acid for use as a dressing for difficult-to-heal wounds. A total of four different dressings were developed, each with different modifications in each layer. The dressing with vitamin C in the third layer was shown to release vitamin C ions more slowly than the dressing with vitamin C in the first layer. The studies conducted have shown that the dressings containing vitamin C have, among other things, a higher compressive strength, are characterised by a lower relative shortening after the application of force and shorten without damage at a lower force than in the case of a dressing without vitamin C. The dressings designed have a very good stability in the temperature range of 18 °C to 60 °C. It was found that the higher the vitamin C content in the dressing, the greater the increase in the specific heat value of the transformations. Therefore, hydrogel dressings containing vitamin C may be candidates for local delivery of vitamin C to the skin and protection of the wound area.

Polyethylene Glycol/Pullulan-Based Carrier for Silymarin Delivery and Its Potential in Biomedical Applications.

Restoring the structures and functions of tissues along with organs in human bodies is a topic gathering attention nowadays. These issues are widely discussed in the context of regenerative medicine. Excipients/delivery systems play a key role in this topic, guaranteeing a positive impact on the effectiveness of the drugs or therapeutic substances supplied. Advances in materials engineering, particularly in the development of hydrogel biomaterials, have influenced the idea of creating an innovative material that could serve as a carrier for active substances while ensuring biocompatibility and meeting all the stringent requirements imposed on medical materials. This work presents the preparation of a natural polymeric material based on pullulan modified with silymarin, which belongs to the group of flavonoids and derives from a plant called Silybum marianum. Under UV light, matrices with a previously prepared composition were crosslinked. Before proceeding to the next stage of the research, the purity of the composition of the matrices was checked using Fourier-transform infrared (FT-IR) spectroscopy. Incubation tests lasting 19 days were carried out using incubation fluids such as simulated body fluid (SBF), Ringer's solution, and artificial saliva. Changes in pH, electrolytic conductivity, and weight were observed and then used to determine the sorption capacity. During incubation, SBF proved to be the most stable fluid, with a pH level of 7.6-7.8. Sorption tests showed a high sorption capacity of samples incubated in both Ringer's solution and artificial saliva (approximately 350%) and SBF (approximately 300%). After incubation, the surface morphology was analyzed using an optical microscope for samples demonstrating the greatest changes over time. The active substance, silymarin, was released using a water bath, and then the antioxidant capacity was determined using the Folin-Ciocâlteu test. The tests carried out proved that the material produced is active and harmless, which was shown by the incubation analysis. The continuous release of the active ingredient increases the biological value of the biomaterial. The material requires further research, including a more detailed assessment of its balance; however, it demonstrates promising potential for further experiments.

Carboxymethyl chitosan/polyacrylamide double network hydrogels based on hydrogen bond cross-linking as potential wound dressings for skin repair

An ideal biomedical hydrogel should imitate natural tissues with high water absorption, high toughness and superior biocompatibility. However, hydrogels constructed from biomolecules such as polysaccharides have low mechanical strength and limited applications. Based on carboxymethyl chitosan (CMCS) and polyacrylamide (PAM), a facile process is presented for preparing double network hydrogels (CMCS/PAM) with improved mechanical properties. According to the systematic characterization, carboxymethyl chitosan and polyacrylamide form a double network hydrogel through hydrogen bonding. The introduction of carboxymethyl chitosan alters the microscopic structure of PAM hydrogel, resulting in a consistent porosity pattern. Hydrogels with double networks exhibit high tensile properties, high stiffness, and good energy dissipation. Furthermore, the hydrogel exhibits effective adhesion to other hydrophilic surfaces. The CMCS/PAM network hydrogels possess excellent properties such as high swelling capacity, injectability, and cellular biocompatibility, making them potentially valuable for biomedical applications.

Methods to achieve tissue-mimetic physicochemical properties in hydrogels for regenerative medicine and tissue engineering.

Hydrogels are water-swollen polymeric matrices with properties that are remarkably similar in function to the extracellular matrix. For example, the polymer matrix provides structural support and adhesion sites for cells in much of the same way as the fibers of the extracellular matrix. In addition, depending on the polymer used, bioactive sites on the polymer may provide signals to initiate certain cell behavior. However, despite their potential as biomaterials for tissue engineering and regenerative medicine applications, fabricating hydrogels that truly mimic the physicochemical properties of the extracellular matrix to physiologically-relevant values is a challenge. Recent efforts in the field have sought to improve the physicochemical properties of hydrogels using advanced materials science and engineering methods. In this review, we highlight some of the most promising methods, including crosslinking strategies and manufacturing approaches such as 3D bioprinting and granular hydrogels. We also provide a brief perspective on the future outlook of this field and how these methods may lead to the clinical translation of hydrogel biomaterials for tissue engineering and regenerative medicine applications.

Bioactive Nb2C MXene-Functionalized Hydrogel with Microenvironment Remodeling and Enhanced Neurogenesis to Promote Skeletal Muscle Regeneration and Functional Restoration.

The complete structure-functional repair of volumetric muscle loss (VML) remains a giant challenge and biomedical hydrogels to remodel microenvironment and enhance neurogenesis have appeared to be a promising direction. However, the current hydrogels for VML repair hardly achieve these two goals simultaneously due to their insufficient functionality and the challenge in high-cost of bioactive factors. In this study, a facile strategy using Nb2C MXene-functionalized hydrogel (OPTN) as a bioactive scaffold is proposed to promote VML repair with skeletal muscle regeneration and functional restoration. In vitro experiments show that OPTN scaffold can effectively scavenge reactive oxygen species (ROS), guide macrophages polarization toward M2 phenotype, and resist bacterial infection, providing a favorable microenvironment for myoblasts proliferation as well as the endothelial cells proliferation, migration, and tube formation. More importantly, OPTN scaffold with electroactive feature remarkably boosts myoblasts differentiation and mesenchymal stem cells neural differentiation. Animal experiments further confirm that OPTN scaffold can achieve a prominent structure-functional VML repair by attenuating ROS levels, alleviating inflammation, reducing fibrosis, and facilitating angiogenesis, newborn myotube formation, and neurogenesis. Collectively, this study provides a highly promising and effective strategy for the structure-functional VML repair through designing bioactive multifunctional hydrogel with microenvironment remodeling and enhanced neurogenesis.

Bioluminescence Resonance Energy Transfer (BRET)-Mediated Protein Release from Self-Illuminating Photoresponsive Biomaterials.

Phototriggered release of various cargos, including soluble protein factors and small molecules, has the potential to correct aberrant biological events by offering spatiotemporal control over local therapeutic levels. However, the poor penetration depth of light historically limits implementation to subdermal regions, necessitating alternative methods of light delivery to achieve the full potential of photodynamic therapeutic release. Here, we introduce a strategy exploiting bioluminescence resonance energy transfer (BRET)-an energy transfer process between light-emitting Nanoluciferase (NLuc) and a photosensitive acceptor molecule-to drive biomolecule release from hydrogel biomaterials. Through a facile, one-pot, and high-yielding synthesis (60-70%), we synthesized a heterobifunctional ruthenium cross-linker bearing an aldehyde and an azide (CHO-Ru-N3), a compound that we demonstrate undergoes predictable exchange of the azide-bearing ligand under blue-green light irradiation (>550 nm). Following site-specific conjugation to NLuc via sortase-tag enhanced protein ligation (STEPL), the modified protein was covalently attached to a poly(ethylene glycol) (PEG)-based hydrogel via strain-promoted azide-alkyne cycloaddition (SPAAC). Leveraging the high photosensitivity of Ru compounds, we demonstrate rapid and equivalent release of epidermal growth factor (EGF) via either direct illumination or via BRET-based bioluminolysis. As NLuc-originated luminescence can be controlled equivalently throughout the body, we anticipate that this unique protein release strategy will find use for locally triggered drug delivery following systemic administration of a small molecule.

Development and Characterization of a Novel Composite Hydrogel Biomaterial for Improved Mucoperiosteal WoundRepair.

Mucoperiosteal wound healing, as it occurs after pediatric cleft palate surgery, can be challenging due to the limitations of current treatments such as tissue flaps secured with sutures and fibrin glue. In this study, we characterized the in vitro performance of a novel composite hydrogel biomaterial designed to be employed as an in situ wound filler and enhance mucoperiosteal wound healing. We evaluated a range of photopolymerizable formulations containing methacrylated gelatin (GelMA), glycol chitosan, and bioglass microparticles. Our aim was to identify one or more formulations with an appropriate balance of properties against a set of functional requirements that we established for this application. To test the formulations against these criteria, we measured photopolymerization kinetics, mechanical properties, degradation rate, in vitro biocompatibility, and ex vivo tissue adhesion. All formulations polymerized in less than 90 s using violet light. In addition, we found that GelMA-based hydrogels were more adhesive to mucoperiosteal tissue than clinical standard fibrin glue. Inclusion of small amounts of bioglass in the formulation increased mechanical compatibility with mucoperiosteal tissue, enhanced cytoconductivity, and promoted cell proliferation. Taken together, our results support the suitability of these photopolymerized composite hydrogels as in situ mucoperiosteal wound fillers. Overall, this study lays the groundwork for investigating the in vivo, pre-clinical effectiveness of these composite hydrogels in improving mucoperiosteal wound healing outcomes.

Hydrogel biomaterials that stiffen and soften on demand reveal that skeletal muscle stem cells harbor a mechanical memory

Muscle stem cells (MuSCs) are specialized cells that reside in adult skeletal muscle poised to repair muscle tissue. The ability of MuSCs to regenerate damaged tissues declines markedly with aging and in diseases such as Duchenne muscular dystrophy, but the underlying causes of MuSC dysfunction remain poorly understood. Both aging and disease result in dramatic increases in the stiffness of the muscle tissue microenvironment from fibrosis. MuSCs are known to lose their regenerative potential if cultured on stiff plastic substrates. We sought to determine whether MuSCs harbor a memory of their past microenvironment and if it can be overcome. We tested MuSCs in situ using dynamic hydrogel biomaterials that soften or stiffen on demand in response to light and found that freshly isolated MuSCs develop a persistent memory of substrate stiffness characterized by loss of proliferative progenitors within the first three days of culture on stiff substrates. MuSCs cultured on soft hydrogels had altered cytoskeletal organization and activity of Rho and Rac guanosine triphosphate hydrolase (GTPase) and Yes-associated protein mechanotransduction pathways compared to those on stiff hydrogels. Pharmacologic inhibition identified RhoA activation as responsible for the mechanical memory phenotype, and single-cell RNA sequencing revealed a molecular signature of the mechanical memory. These studies highlight that microenvironmental stiffness regulates MuSC fate and leads to MuSC dysfunction that is not readily reversed by changing stiffness. Our results suggest that stiffness can be circumvented by targeting downstream signaling pathways to overcome stem cell dysfunction in aged and disease states with aberrant fibrotic tissue mechanics.

Well-Defined Synthetic Copolymers with Pendant Aldehydes Form Biocompatible Strain-Stiffening Hydrogels and Enable Competitive Ligand Displacement.

Dynamic hydrogels are attractive platforms for tissue engineering and regenerative medicine due to their ability to mimic key extracellular matrix (ECM) mechanical properties like strain-stiffening and stress relaxation while enabling enhanced processing characteristics like injectability, 3D printing, and self-healing. Systems based on imine-type dynamic covalent chemistry (DCvC) have become increasingly popular. However, most reported polymers comprising aldehyde groups are based on either end-group-modified synthetic or side-chain-modified natural polymers; synthetic versions of side-chain-modified polymers are noticeably absent. To facilitate access to new classes of dynamic hydrogels, we report the straightforward synthesis of a water-soluble copolymer with a tunable fraction of pendant aldehyde groups (12-64%) using controlled radical polymerization and their formation into hydrogel biomaterials with dynamic cross-links. We found the polymer synthesis to be well-controlled with the determined reactivity ratios consistent with a blocky gradient microarchitecture. Subsequently, we observed fast gelation kinetics with imine-type cross-linking. We were able to vary hydrogel stiffness from ≈2 to 20 kPa, tune the onset of strain-stiffening toward a biologically relevant regime (σc ≈ 10 Pa), and demonstrate cytocompatibility using human dermal fibroblasts. Moreover, to begin to mimic the dynamic biochemical nature of the native ECM, we highlight the potential for temporal modulation of ligands in our system to demonstrate ligand displacement along the copolymer backbone via competitive binding. The combination of highly tunable composition, stiffness, and strain-stiffening, in conjunction with spatiotemporal control of functionality, positions these cytocompatible copolymers as a powerful platform for the rational design of next-generation synthetic biomaterials.

Hydrogel dressings on neurotrophic keratitis in an experimental animal model.

To investigate the therapeutic effects of hydrogel dressings on neurotrophic keratitis in rats. Male Wistar rats, aged 42-56d, were randomly divided into control, experimental, and treatment groups, each consisting of five rats. The experimental and treatment groups underwent neurotrophic keratitis modeling in both eyes. After successful modeling, biomedical hydrogels formed with polyvinyl alcohol and polyvinyl pyrrolidone were used in treatment group for 7d. Ocular irritation response and keratitis index scores, Schirmer's test, tear film break-up time (BUT), sodium fluorescein staining, and hematoxylin and eosin (HE) staining were used to evaluate the effectiveness of the treatment. The neurotrophic keratitis model was successfully established in rats with severe ophthalmic nerve injury, characterized by keratitis, ocular irritation, reduced tear secretion measured by decreased BUT and Schirmer test values, corneal epithelial loss, and disorganized collagen fibers in the stromal layer. Following treatment with hydrogel dressings, significant improvements were observed in keratitis scores and ocular irritation symptoms in model eyes. Although the recovery of tear secretion, as measured by the Schirmer's test, did not show statistical differences, BUT was significantly prolonged. Fluorescein staining confirmed a reduction in the extent of corneal epithelial loss after treatment. HE staining revealed the restoration of the structural disorder in both the epithelial and stromal layers to a certain extent. Hydrogel dressing reduces ocular surface irritation, improves tear film stability, and promotes the repair and restoration of damaged epithelial cells by maintaining a moist and clean environment on the ocular surface in the rat model.

Hybrid biomaterial hydrogel loading iRGD&PS double modified lipid nanoparticles ameliorates diabetic wound healing through promoting efferocytosis and glycolysis-related macrophage reprogramming

Efferocytosis is a critical process whereby macrophages residing in the wound area play a key role in the efficient clearing and degradation of apoptotic neutrophils. This process is followed by a phenotypic transition toward an anti-inflammatory state, essential for inflammation resolution and tissue repair. The cystine/glutamate antiporter SLC7A11 has recently been identified as an inhibitor of efferocytosis, and its blockade has been found to enhance wound healing. In this study, we demonstrated that tiliroside, a plant-derived glycoside containing flavones, binds directly to SLC7A11 and pyruvate kinase isozyme M2 (PKM2). This was established by molecular docking predictions and activity-based protein profiling (ABPP). Cytological experiments revealed that tiliroside promoted the process of efferocytosis and led to glycolysis-related macrophage reprogramming. To facilitate targeted drug delivery to macrophages at diabetic wound sites, we designed a novel hybrid biomaterial. This hybrid biomaterial, prepared as Gel@Til iRGD&PS@PLGA NPs is manufactured by loading tiliroside (Til)-conjugated iRGD&PS double modified lipid nanoparticles (iRGD&PS@PLGA NPs) into a pH-responsive hydrogel matrix. The administration of Gel@Til iRGD&PS@PLGA NPs in diabetic cutaneous wound models has been shown to significantly promote tissue regeneration through the promotion of efferocytosis and glycolysis-related macrophage reprogramming. Therefore, this study introduces a novel approach to diabetic wound management by leveraging the promotion of efferocytosis.

The Role of Hydrogel Biomaterials in the Intervention of Wound Healing and Skin Regeneration via Exosomes: A Systematic Review and Meta-Analysis of Preclinical Animal Studies.

Significance: The combination of hydrogel biomaterials with exosomes to facilitate wound healing and skin regeneration is a promising approach. Recent Advances: Recent preclinical animal studies have focused on investigating the efficacy of hydrogel-based delivery systems for exosomes in promoting wound healing and skin regeneration. Critical Issues: Despite encouraging results, critical issues remain unresolved, such as optimizing hydrogel properties to enhance the efficacy of combined therapy with exosomes for wound and bridging the translational gap between preclinical and clinical applications. Future Directions: Future research endeavors should concentrate on refining hydrogel design to enhance exosome delivery efficacy, conducting rigorous clinical trials to assess the safety and efficacy of exosome-loaded hydrogels in human wound healing and skin regeneration, and exploring innovative strategies to maximize therapeutic outcomes.

Permselectivity of Silk Fibroin Hydrogels for Advanced Drug Delivery Neurotherapies.

A promising trend in tissue engineering is using biomaterials to improve the control of drug concentration in targeted tissue. These vehicular systems are of specific interest when the required treatment time window is higher than the stability of therapeutic molecules in the body. Herein, the capacity of silk fibroin hydrogels to release different molecules and drugs in a sustained manner was evaluated. We found that a biomaterial format, obtained by an entirely aqueous-based process, could release molecules of variable molecular weight and charge with a preferential delivery of negatively charged molecules. Although the theoretical modeling suggested that drug delivery was more likely to be driven by Fickian diffusion, the external media had a considerable influence on the release, with lipophilic organic solvents such as acetonitrile-methanol (ACN-MeOH) intensifying the release of hydrophobic molecules. Second, we found that silk fibroin could be used as a vehicular system to treat a variety of brain disorders as this biomaterial sustained the release of different factors with neurotrophic (brain-derived neurotrophic factor) (BDNF), chemoattractant (C-X-C motif chemokine 12) (CXCL12), anti-inflammatory (TGF-β-1), and angiogenic (VEGF) capacities. Finally, we demonstrated that this biomaterial hydrogel could release cholesteronitrone ISQ201, a nitrone with antioxidant capacity, showing neuroprotective activity in an in vitro model of ischemia-reoxygenation. Given the slow degradation rate shown by silk fibroin in many biological tissues, including the nervous system, our study expands the restricted list of drug delivery-based biomaterial systems with therapeutic capacity for both short- and especially long-term treatment windows and has merit for use with brain pathologies.

High-strength and high-elasticity silk fibroin-composite gelatin biomaterial hydrogels for rabbit knee cartilage regeneration

Suitable hydrogel materials for cartilage tissue repair should exhibit high strength and toughness, and excellent biocompatibility. However, the mechanical properties of most hydrogels cannot meet the complex mechanical requirements of articular cartilage tissues. Given this situation, we have adopted a chemical cross-linking method using hexafluoro isopropanol to mediate the cross-linking of Silk Fibroin (SF) and deionized water (DI), which promoted the formation of β-sheets, generating “high-toughness” Silk Fibroin hydrogels. The introduction of Gelatin (Gel) served to increase the content of β-sheets and increase the tensile modulus from 24.51 ± 2.07 MPa to 39.75 ± 6.54 MPa, which significantly enhanced the flexibility of the hydrogel and meets the mechanical requirements of cartilage tissue. In addition, in vitro biological experiments have shown that the introduction of Gel promotes cell proliferation and enhances the production of cartilage extracellular matrix by chondrocytes. In vivo experiments have demonstrated that SF/Gel hydrogel promotes articular cartilage regeneration more effectively than SF hydrogel, as evidenced by improvements in gross appearance, imaging, and histology. This study has established that high-strength SF/Gel hydrogel prepared by applying the binary-solvent-induced conformation transition strategy has potential applications in cartilage tissue repair and regeneration and is a feasible biomaterial for osteochondral regeneration.

Superb Silk Hydrogels with High Adaptability, Bioactivity, and Versatility Enabled by Photo-Cross-Linking.

The exceptional biocompatibility and adaptability of hydrogels have garnered significant interest in the biomedical field for the fabrication of biomedical devices. However, conventional synthetic hydrogels still exhibit relatively weak and fragile properties. Drawing inspiration from the photosynthesis process, we developed a facile approach to achieve a harmonious combination of superior mechanical properties and efficient preparation of silk fibroin hydrogel through photo-cross-linking technology, accomplished within 60 s. The utilization of riboflavin and H2O2 enabled a sustainable cyclic photo-cross-linking reaction, facilitating the transformation from tyrosine to dityrosine and ultimately contributing to the formation of highly cross-linked hydrogels. These photo-cross-linking hydrogels exhibited excellent elasticity and restorability even after undergoing 1000 cycles of compression. Importantly, our findings presented that hydrogel-encapsulated adipose stem cells possess the ability to stimulate cell proliferation along with stem cell stemness. This was evidenced by the continuous high expression levels of OCT4 and SOX2 over 21 days. Additionally, the utilization of photo-cross-linking hydrogels can be extended to various material molding platforms, including microneedles, microcarriers, and bone screws. Consequently, this study offered a significant approach to fabricating biomedical hydrogels capable of facilitating real-time cell delivery, thereby introducing an innovative avenue for designing silk devices with exceptional machinability and adaptability in biomedical applications.

Tailoring Network Topology in Mechanically Robust Hydrogels for 3D Printing and Injection.

Tissue engineering and regenerative medicine are confronted with a persistent challenge: the urgent demand for robust, load-bearing, and biocompatible scaffolds that can effectively endure substantial deformation. Given that inadequate mechanical performance is typically rooted in structural deficiencies─specifically, the absence of energy dissipation mechanisms and network uniformity─a crucial step toward solving this problem is generating synthetic approaches that enable exquisite control over network architecture. This work systematically explores structure-property relationships in poly(ethylene glycol)-based hydrogels constructed utilizing thiol-yne chemistry. We systematically vary polymer concentration, constituent molar mass, and cross-linking protocols to understand the impact of architecture on hydrogel mechanical properties. The network architecture was resolved within the molecular model of Rubinstein-Panyukov to obtain the densities of chemical cross-links and entanglements. We employed both nucleophilic and radical pathways, uncovering notable differences in mechanical response, which highlight a remarkable degree of versatility achievable by tuning readily accessible parameters. Our approach yielded hydrogels with good cell viability and remarkably robust tensile and compression profiles. Finally, the hydrogels are shown to be amenable to advanced processing techniques by demonstrating injection- and extrusion-based 3D printing. Tuning the mechanism and network regularity during the cell-compatible formation of hydrogels is an emerging strategy to control the properties and processability of hydrogel biomaterials by making simple and rational design choices.

One-step soaking strategy toward mechanobiological double-network hydrogel with improving chondrogenesis capacity

Cartilage tissue engineering (CTE) is a promising strategy for addressing the persistent challenges in healing articular cartilage defects in the clinic, aiming to manufacture scaffolds with ideal mechanical characteristics that can provide a conducive microenvironment for the reconstruction or replacement of damaged cartilage defects. Easy operation, excellent mechanical strength, remarkable biocompatibility, and inherent capacity to promote cartilage formation are essential in CTE. This study designed a mechanobiological double-network (DN) hydrogel (KCS-PAA-Mn2+) through a one-step soaking strategy of immersing the composite hydrogel (KCS-PAA) of kartogenin (KGN)-conjugated short-chain chitosan (CS) covalent with polyacrylic acid (PAA) in manganese chloride (MnCl2) solution. Due to the strong physical interactions of CS chain-entanglement network and carboxylate-Mn2+ complex inducing polymer aggregation state transitions, the KCS-PAA-Mn2+ DN hydrogel exhibited exceptional mechanical characteristics, such as high tensile property (strength: 0.24 MPa at a strain of 552 %; toughness: 0.66 MPa), compressibility (strength: 51.98 MPa at a strain of 95 %; compressive modulus: 0.09 MPa), controllable swelling behavior (~327 %), and sustained drug release (>2 weeks). Moreover, in vitro biological studies demonstrated that the KCS-PAA-Mn2+ DN hydrogel not only promoted cell growth and proliferation but also enhanced the expression of genes specific to cartilage and the release of cartilage extracellular matrix (ECM) by bone mesenchymal stem cells (BMSCs), thus enabling a continuous concentration for a long period and persistently enhancing its chondrogenic efficiency. Overall, this soaking methodology reported here is universal to construct mechanically bioactive scaffolds that could expand their bio-applicability with simultaneous advantages of mechanical supports, tailorable swelling, sustainable drug release and long-lasting biological function, thus facilitating the advancement of cartilage-engineered hydrogel biomaterials to a higher level.

Hydrogel Ink for 3D Printing with High and Widely Tunable Mechanical Properties via the Salting‐Out Effect

AbstractDue to the difficulty of simultaneously ensuring printability and controlling their mechanical properties, 3D printed hydrogels thus far have low modulus, far less than that of many biological tissues and organs. Therefore, their feasibility toward various biomimetic applications is currently limited. Herein, Direct‐Ink‐Writing (DIW) based 3D printable hydrogel ink with broadly adjustable mechanical properties is introduced. The salting‐out effect is utilized to effectively lower the gelation temperature of hydrogel inks with a wide range of modulus (0.193–1.072 MPa), making them all 3D printable. As a proof of concept, multi‐layered synthetic blood vessels that mimic the mechanical properties of biological blood vessels are printed, and their practicability toward surgical training is demonstrated. The versatility and simplicity of this technique make it highly promising for use in various 3D‐printed hydrogel biomaterials applications.

A Comprehensive Review on Novel Polymer Biomaterials for Hydrogel-Based Drug Delivery System

Abstract: Hydrogel biomaterials, which are formed from polymers generated from either natural or synthetic sources, are characterized by their mechanical stability as well as their biological acceptability. Hydrogels are characterized by properties such as a high swelling index, biocompatibility, the ability to be easily manipulated, flexibility, and rapid degradation. Hydrogels are commonly used as drug carriers due to the fact that they are simple to produce and may be applied by themselves. Using hydrogels in drug delivery applications, where gel-based nanocarriers carry drug molecules to the area of interest in living tissues. The research community is interested in doing this because of the unique physical and chemical properties that hydrogels possess. It has been discussed that several new hydrogel-based solutions are being employed for the administration of drugs that are not taken orally. Hydrogel systems can be developed for use in either passive or active drug administration, making them suitable for a broad variety of settings and applications. In addition to possessing essential biocompatible properties, hydrogels are able to move freely within the human body without having any visible impact on the surrounding environment. The present review has been developed to examine novel concepts linked to hydrogels and their delivery mechanism. This is due to the fact that hydrogels possess qualities that are both unique and novel. In this article, the mechanics of drug delivery systems that are based on hydrogels are detailed. These processes include loading, releasing, and targeting. For these components, the development and investigation of cutting-edge hydrogel- based delivery systems is necessary.

In Vitro Characterization of Poly(Ethylene Glycol) Dimethacrylate-Nanofibrillated Cellulose as an Injectable Biomaterial for Herniated Nucleus Pulposus Substitute

Highlights:1. Novel synthetic biopolymer hydrogels were successfully prepared from pristine poly(ethylene glycol) dimethacrylate (PEGDMA) and nanofibrillated cellulose (NFC) using the photopolymerization method.2. PEGDMA-NFC biocomposite hydrogel can be developed as an affordable biomaterial for herniated nucleus pulposus substitute, with the potential to meet clinical application standards. Abstract Herniated nucleus pulposus develops when the intervertebral disc portudes through the annulus fibrosus due to the rupture of the annulus fibrosus or a decrease in proteoglycans. Hydrogel implant material can be injected into the disc space to restore disc thickness caused by disc degeneration with minimal invasiveness. This study aimed to characterize poly(ethylene glycol) dimethacrylate-nanofibrillated cellulose (PEGDMA-NFC) in vitro as a potential biomaterial for herniated nucleus pulposus substitute. This study utilized PEGDMA-NFC to treat first-degree herniated nucleus pulposus using the photopolymerization method. PEGDMA was selected because of its hydrophilic ability to produce hydrogel. The addition of NFC to the PEGDMA precursor was expected to show mechanical properties as a hydrogel bio composite candidate. The characterization of PEGDMA-NFC was conducted using three tests: Fourier-transform infrared spectroscopy (FTIR), viscosity assessment, and an in vitro injection testing model. The normal distribution of the data was analyzed using the Kolmogorov-Smirnov test, while the homogeneity was assessed using Levene's test. Homogenous and normally distributed data were analyzed using a one-way analysis of variance (ANOVA) with a p-value of <0.05. The explored concentrations of PEGDMA-NFC included a ratio of 1:0 for the control samples and ratios of 1:0.5 (K1), 1:0.75 (K2), and 1:1 (K3) for the experimental samples. The FTIR analysis revealed the presence of various functional groups in PEGDMA-NFC, indicating its potential classification as a hydrogel biomaterial. The characterization data showed that the K3 sample yielded the most favourable outcome with a viscosity value of 74.67 dPa·s. From the in vitro injection testing result, the addition of NFC demonstrated that the hydrogel would not rupture when released from the mold. The hydrogel could be injected with an 18 gauge needle. The statistical analysis results showed a significant difference among the samples (p<0.05). This study concludes that the PEGDMA-NFC hydrogel biocomposite can be effectively applied in herniated nucleus pulposus cases.