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Elevation of early-stage gastrointestinal cancer using submucosal injection materials (SIMs) and postoperative wound care with adhesive materials are crucial for preventing complications arising from endoscopic submucosal dissection (ESD). Several types of SIMs have been developed; however, they often provide insufficient tissue elevation and fail to adequately adhere to the defect following the removal of early-stage gastrointestinal cancer. In this study, we present the development of injectable Cat-PBA-ApGltn hydrogels, which are based on catechol group-modified Alaska pollock gelatin (Cat-ApGltn) and phenylboronic acid-modified Alaska pollock gelatin (PBA-ApGltn), serving as multifunctional SIMs. A Cat-ApGltn/PBA-ApGltn mixed solution formed a hydrogel within 3 seconds. The resulting Cat-PBA-ApGltn hydrogels were easily injected manually through a 23 G needle due to their shear-thinning properties. Additionally, 10 w/v% Cat-PBA-ApGltn hydrogels demonstrated a 2.3-fold increase in mucosal elevation (7.2 ± 0.4 mm) compared with a commercially available SIM (3.1 ± 0.7 mm). The 10 w/v% Cat-PBA-ApGltn hydrogel, when adhered to porcine gastric submucosa, exhibited a burst strength 7 times greater than the average human intragastric pressure. Furthermore, the Cat-PBA-ApGltn hydrogels demonstrated biodegradability without inducing severe inflammation upon implantation in rat subcutaneous tissue. These Cat-PBA-ApGltn hydrogels hold promise as multifunctional SIMs, boasting injectability, excellent elevation, adhesion capabilities, and biodegradability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Injectable hydrogels have wide applications in clinical practice. However, the development of tough and bioadhesive ones based on biopolymers, along with biofriendly and robust crosslinking strategies, still represents a great challenge. Herein, we report an injectable hydrogel composed of maleimidyl alginate and pristine gelatin, for which the precursor solutions could self-crosslink via mild Michael-type addition without any catalyst or external energy upon mixing. This hydrogel is tough and bioadhesive, which can maintain intactness as well as adherence to the defect of porcine skin under fierce bending and twisting, warm water bath, and boiling water shower. Besides, it is biocompatible, bioactive and biodegradable, which could support the growth and remodeling of cells by affording an extracellular matrix-like environment. As a proof of application, we demonstrate that this hydrogel could significantly accelerate diabetic skin wound healing, thereby holding great potential in healthcare., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Gelatin-based injectable hydrogels capable of encapsulating cells are pivotal in tissue engineering because they can conform to any geometry and exhibit physical properties similar to those of living tissues. However, the slow gelation process observed in these cell-encapsulating hydrogels often causes an uneven dispersion of cells. This study proposes an approach for achieving fast gelation of unmodified gelatin under physiological conditions through gelatin preclustering. By using tetrafunctional succinimidyl-terminated poly(ethylene glycol) as a clustering agent, the gelation process is successfully expedited fivefold without requiring chemical modifications, effectively addressing the associated challenges of uneven cell distribution., (© 2024 The Authors. Macromolecular Bioscience published by Wiley‐VCH GmbH.)

Treating the most widespread complication of diabetes: diabetic wounds poses a significant clinical obstacle due to the intricate nature of wound healing in individuals with diabetes. Here a novel approach is proposed using easily applicable injectable gelatin/metal/tea polyphenol double nanonetworks, which effectively remodel the wound microenvironment and accelerates the healing process. The gelatin(Gel) crosslink with metal ions (Zr 4+ ) through the amino acids, imparting advantageous mechanical properties like self-healing, injectability, and adhesion. The nanonetwork's biological functions are further enhanced by incorporating the tea polyphenol metal nanonetwork through in situ doping of the epigallocatechin gallate (EGCG) with great antibacterial, self-healing, antioxidant, and anticancer capabilities. The in vitro and in vivo tests show that this double nanonetworks hydrogel exhibits faster cell migration and favorable anti-inflammatory and antioxidant properties and can greatly reshape the microenvironment of diabetic wounds and accelerate the wound healing rate. In addition, this hydrogel is completely degraded after subcutaneous injection for 7 days, with nondetectable cytotoxicity in H&E staining of major mice organs and the serum level of liver function indicators. Considering the above-mentioned merits of this hydrogel, it is believed that the injectable gelatin/metal/tea polyphenol double nanonetworks have broad biomedical potential, especially in diabetic wound repair and tissue engineering., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Animal-derived basement-membrane matrices such as Geltrex are used to grow cells and tissues. Particularly, these are commonly applied to support tumor growth in animals for cancer research. However, a material derived from an animal source has an undefined composition, and may thus have unavoidable batch-to-batch variation in properties. To overcome these issues, a series of synthetic short peptides to form hydrogels is designed in combination with gelatin to promote cell adhesion and growth. The peptides have sequences of (X1Y1X2Y2) 2 , where X1 and X2 are hydrophobic residues, while Y1 and Y2 are hydrophilic residues. The peptides spontaneously fold and self-assemble into a β-sheet secondary structure upon contact with salts, and then aggregate to form hydrophilic networks of hydrogels. Hybrid hydrogels formed by mixing the peptide IEVEIRVK (IVK8) with gelatin are injectable and enzymatically degradable. The hybrid hydrogels at optimal compositions support SW480 and HepG2 tumor spheroid growth in vitro as effectively as Geltrex. More importantly, the peptide/gelatin hydrogels support tumor growth in a SW480 human colorectal adenocarcinoma xenograft mouse model. Altogether, the results illustrate that the synthetic peptide/gelatin hybrid hydrogel is a promising scaffold that can be used to support cell and tissue growth both in vitro and in vivo., (© 2023 Wiley-VCH GmbH.)

Shear-thinning hydrogels are suitable biomaterials for catheter-based minimally invasive therapies; however, the tradeoff between injectability and mechanical integrity has limited their applications, particularly at high external shear stress such as that during endovascular procedures. Extensive molecular crosslinking often results in stiff, hard-to-inject hydrogels that may block catheters, whereas weak crosslinking renders hydrogels mechanically weak and susceptible to shear-induced fragmentation. Thus, controlling molecular interactions is necessary to improve the cohesion of catheter-deployable hydrogels. To address this material design challenge, we have developed an easily injectable, nonhemolytic, and noncytotoxic shear-thinning hydrogel with significantly enhanced cohesion via controlling noncovalent interactions. We show that enhancing the electrostatic interactions between weakly bound biopolymers (gelatin) and nanoparticles (silicate nanoplatelets) using a highly charged polycation at an optimum concentration increases cohesion without compromising injectability, whereas introducing excessive charge to the system leads to phase separation and loss of function. The cohesive biomaterial is successfully injected with a neuroendovascular catheter and retained without fragmentation in patient-derived three-dimensionally printed cerebral aneurysm models under a physiologically relevant pulsatile fluid flow, which would otherwise be impossible using the noncohesive hydrogel counterpart. This work sheds light on how charge-driven molecular and colloidal interactions in shear-thinning physical hydrogels improve cohesion, enabling complex minimally invasive procedures under flow, which may open new opportunities for developing the next generation of injectable biomaterials.

A hydrogel carrier was prepared by synergistic cross-linking of dynamic imine bonds and hydrogen bonds between gelatin and dialdehyde starch (DS). The dynamic gelation process and rheological and mechanical properties of hydrogels with different concentrations of DS were studied by dynamic rheology and texture analysis. By changing the content of DS, the gelation kinetics of the hydrogel were adjusted to determine the different gelation times and ensure good injectability. Hydrogels have a stable and firm network structure, and the network can regenerate rapidly after dissociation and collapse. The hydrogel had self-recovery and fatigue resistance, and its hardness, elasticity, deformation capacity, compressive strength and modulus increased with increasing DS content. The hydrogel had good pH-dependent controlled-release ability for curcumin. Injectable hydrogels with biocompatibility, tunable mechanical properties and self-healing properties were used as drug or nutrient delivery carriers for more controlled placement and release., (Copyright © 2022. Published by Elsevier Ltd.)

Acute skin injury should be treated in time, due to many factors will affect the normal healing process of wounds, hinder tissue regeneration, and eventually form chronic wounds. Herein, an injectable, in-situ gel-forming hydrogel has been fabricated. The hydrogel is stabilized by dynamic Schiff base and composed of gelatin (Gel), oxidized dextran (Odex) and apocynin (Apo). In vitro studies have shown that this hydrogel has good injectability, plasticity, self-healing and efficient hemostatic properties. The hydrogel has good cytocompatibility with HaCaT and L929 cells by the Live/Dead cell staining. Furthermore, in vivo studies have shown that hydrogel loaded with APO can accelerate angiogenesis and skin tissue regeneration by reducing wound inflammation. Therefore, the injectable Gel/Odex/Apo hydrogel has the advantages of simple preparation process, convenient use and multifunction, etc., it is a promising wound dressing for full-thickness skin repair and has great potential in the field of skin tissue regeneration., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Gelatin is one of the most versatile biopolymers in various biomedical applications. A gelatin derivative gelatin-catechol (Gel-C) was developed in this study to further optimize its chemical and physical properties such as thermal reversibility and injectability. We found that Gel-C remains in a solution state at room temperature, and the temperature-dependent gelation capability of gelatin is well preserved in Gel-C. Its gel-forming temperature decreased to about 10 °C (about 30 °C for gelatin), and a series of gelatin derivatives with different gel-forming temperatures (10-30 °C) were formed by mixing gelatin and Gel-C in different ratios. Additionally, irreversible Gel-C hydrogels could be made without the addition of external stimuli by combining the physical cross-linking of gelatin and the chemical cross-linking of catechol. At the same time, properties of Gel-C hydrogels such as thermal reversibility and injectability could be manipulated by controlling the temperature and pH of the precursor solution. By simulating the formation of an irreversible Gel-C hydrogel in vivo , an in situ gelling system was fabricated by lowering the local temperature of the hydrogel with cold shock, thus realizing targeted and localized molecular delivery with prolonged retention time. This simple system integrated with the temperature responsiveness of gelatin and chemical cross-linking of catechol groups thus provides a promising platform to fabricate an in situ gelling system for drug delivery.

Traumatic brain injury (TBI) is one of the most devastating nervous injuries. Neural tissue engineering based on stem cells and bioactive scaffold is a promising but challenging approach for neural repair. A cutting-edge system with capability to control the fate of encapsulated stem cells is attractive to enhance neural regeneration after TBI. Herein, an injectable gelatin hydrogel dual-enzymatically cross-linked by horse radish peroxidase (HRP) and choline oxidase (ChOx) was performed as the neural scaffold to load murine bone marrow-derived mesenchymal stem cells (BMSC) for TBI treatment. The results of in vitro cellular experiments showed that low cross-linked gelatin hydrogel could obviously promote cellular viability, neural differentiation, and neurotrophins secretion of the loaded BMSC. In vivo tests on a TBI model of C57BL/6 mouse demonstrated that BMSC-laden gelatin hydrogel implants could significantly reduce the damaged area, ameliorate inflammation, attenuate neuronal apoptosis, facilitate survival and proliferation of endogenous neural cells, and promote the neurological function recovery of TBI mice. All data suggest that establishment of this three-dimensional (3D) gelatin hydrogel stem cell-loaded system is a promising therapeutic strategy for TBI or other neurological rehabilitation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Biomaterials for effective hemorrhage control are urgently needed in clinics as uncontrolled bleeding is associated with high mortality. Herein, we developed an injectable and in situ photo-crosslinkable hybrid hemostatic hydrogel by combining pectin methacrylate (PECMA) and gelatin methacryloyl (GelMA). This modular material system combines ionic- and photo-crosslinking chemistries to design interpenetrating networks (IPN) exhibiting tunable rheology, highly porous structure, and controllable swelling and mechanical properties. By simply changing the calcium (0-15 mM) and polymer (1.5-7%) content used for the sequential crosslinking of hydrogels via calcium gelation and UV-photopolymerization, it was possible to precisely modulate the injectability, degradation, and swelling ratio. Moreover, it is demonstrated that PECMA/GelMA hydrogels present good cytocompatibility and uniquely synergize the hemostatic properties of calcium ions on PECMA, the amine residues on GelMA, and the highly porous network toward rapid blood absorption and fast coagulation effect. An in vitro porcine skin bleeding model confirmed that the hydrogel could be directly injected into the wound and rapidly photo-crosslinked, circumventing the bleeding and decreasing the coagulation time by 39%. Importantly, the crosslinked hydrogel could be easily removed to prevent secondary wound injury. Overall, this injectable hybrid PECMA/GelMA hydrogel stands as a promising hemostatic material., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Injectable hydrogels with conductivity are highly desirable as scaffolds for the engineering of various electrical stimuli-responsive tissues, including nerve, muscle, retina, and bone. However, oxygen deprivation within scaffolds can lead to failure by causing cell necrosis. Therefore, an oxygen release conductive injectable hydrogel can serve as a promising support for the regeneration of such tissues. In the present study, H 2 O 2 -loaded polylactic acid microparticles were fabricated. Then, gelatin-graft-polypyrrole with various pyrrole contents and periodate-oxidized pectin were synthesized, and consequently, injectable conductive hydrogel/microparticle scaffolds, inside which catalase was grafted and trapped, were obtained. The results revealed that spherical particles with a mean diameter of 60.39 μm and encapsulation efficiency of 49.64 %, which persistently provided oxygen up to 14 days, were achieved. Investigations on hydrogels revealed that with the increase of pyrrole content of gelatin-graft-polypyrrole from 0 to 15 %, the swelling ratio, pore size, porosity, and conductivity were increased from 6.5 to 11.8, 173.13 μm-295.96 μm, 79.7%-93.8%, and from 0.06 mS/m to 2.14 mS/m, respectively. On the other hand, the crosslinking degree and compressive modulus of hydrogels were shown to decrease from 67.24%-27.35%, and from 214.1 kPa to 64.4 kPa, respectively. Moreover, all formulations supported cell viability and attachment. Overall, the hydrogel/particle scaffold with the merits of electrical conductivity, injectability, compatibility, and sustained oxygen release can be used as a tissue engineering scaffold, promoting the regeneration of electricity responsive tissues. Considering all the aforementioned characteristics and behavior of the fabricated scaffolds, they may be promising candidates for bone tissue engineering applications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The development of minimally invasive surgery has created a demand for ideal medical adhesives exhibiting biocompatibility, biodegradability, antimicrobial activity, and strong adhesion to tissues in wet environments. However, as clinically approved surgical tissue glues suffer from poor adhesion activation, limited adhesion strength, and toxicity, novel tissue glues are highly sought after. Herein, a mussel-inspired injectable hydrogel was prepared from catechol- and methacrylate-modified chitosan/gelatin and shown to exhibit biocompatibility, inherent antimicrobial activity, and good adhesion to wet tissues. Moreover, as this gel could be applied onto tissue surfaces and cured in situ within seconds of body contact by a biocompatible and multifunctional redox initiator (H 2 O 2 -ascorbic acid), it was concluded to be a promising surgical sealant and wound dressing (even for infected wounds) accelerating wound healing., (Copyright © 2020. Published by Elsevier Ltd.)

Fibrin glue has been widely used as a surgical sealing and hemostatic agent. Its application is restricted due to poor tissue adhesion and low mechanical strength. To develop better tissue sealant and hemostatic agent, this study prepared the injectable hydrogels by chemically cross-linking gelatin (G) with or without hyaluronic acid (HA) in situ at a mild condition. The rheological analysis, Fourier transform infrared spectroscopy, swelling, proteolytic degradation, biocompatibility, tissue sealing, and hemostatic ability of the hydrogels were investigated. It was found that the chemical cross-linking rapidly formed in both self-crosslinking gelatin (sc-G) and gelatin/hyaluronate acid (G/HA) hydrogels. The hydrogels could be degraded by trypsin and had a desirable biocompatibility. The tissue sealing ability of the hydrogels was superior to fibrin glue. Furthermore, the G/HA hydrogel had similar hemostatic performance as fibrin glue, and was better than that of gelatin hydrogel. The results in the study indicated that the G/HA hydrogel could be used in clinic as a tissue sealant or surgical hemostat., (© 2019 Wiley Periodicals, Inc.)

The objective of this study is to design bioabsorbable injectable hydrogels based on the physico-chemical interaction between biocompatible polymers and ferric ions, and evaluate the survival, proliferation, and osteogenic differentiation of cells encapsulated in the hydrogels. The injectable hydrogels were prepared by simply mixing mixed alginate/gelatin solution at various ratios and FeCl 3 solution. The hydrogels prepared disappeared within a few days in the phosphate buffered-saline solution (PBS) with containing collagenase although the disappearance rate increased with an increase of the gelatin ratio in the hydrogel. For the hydrogel of alginate/gelatin low ratio, the survival and proliferation of cells in the hydrogel-encapsulated condition were significantly high compared with those of hydrogel at the higher ratios. The cells collected 3 days after cultured in the hydrogel also proliferated to a significantly higher extent than those collected from other hydrogels. The proliferation ability of cells was similar that of cells cultured on the standard tissue culture polystyrene (TCPS) dish. When evaluated to compare with cells cultured on the TCPS dish, the expression of runt-related transcription factor-2 (RUNX2) gene, the alkaline phosphatase (ALP) activity, and the calcium precipitation were significantly high. The cells were encapsulated by the mixed alginate/gelatin and FeCl 3 hydrogel and injected in the back subcutis of mice, the percentage of cells retained in the injected site was higher than that of cells injected in the PBS suspension. It is concluded that the injectable hydrogel prepared by simple mixing mixed alginate/gelatin solution and FeCl 3 solution is a promising material for the cell transplantation. STATEMENT OF SIGNIFICANCE: Injectable hydrogels prepared by simple mixing mixed alginate/gelatin solution at various ratios and FeCl 3 solution. For the hydrogel of alginate/gelatin low ratio, the survival, the proliferation, and the differentiate properties of cells in the hydrogel-encapsulated condition were similar those of cells cultured on the TCPS dish. When the cells encapsulated hydrogels were injected in the back subcutis of mice, the percentage of cells retained in the injected site was higher than that of cells injected in the PBS suspension. It is concluded that the present injectable hydrogel is a promising material for the cell transplantation., (Copyright © 2019. Published by Elsevier Ltd.)

There is still an enormous demand for designing materials to the treatment of Parkinson's disease, and dopamine-based injectable polysaccharide hydrogels as localized drug delivery system have huge potential. Here, we developed a facile approach to prepare dopamine-based and polydopamine crosslinked injectable hydrogels by simply oxidizing a mixture of quaternized chitosan, gelatin and dopamine under physiological conditions. These injectable hydrogels showed stable mechanical strength by rheometer and exhibited good degradability evaluated by in vitro degradation test. The chemical structure and morphology of the hydrogels were characterized by FT-IR and SEM. Dopamine as a drug for treating Parkinson's disease and metronidazole as an anti-inflammatory drug were encapsulated in the hydrogel. The release profiles indicated that the injectable hydrogels have great capacity as a carrier for long-term localized release system for dopamine and metronidazole. Furthermore, the cytocompatibility of the hydrogels was confirmed by cell viability and proliferation assays using mouse L929 fibroblast cells. This work provides a new and facile approach to prepare dopamine-based injectable materials which can be used as long-term injectable sustained release system for dopamine as well as anti-inflammatory drug for Parkinson's treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Injectable biomaterials are attractive for soft tissue regeneration because they are handled in a minimally invasive manner and can easily adapt to complex defects. However, inadequate vascularization of the injectable constructs has long been a barrier, leading to necrosis or volume reduction after implantation. In this work, we developed a three-step process to synthesize injectable gelatin-derived hydrogels that are capable of controlling growth factor delivery to induce angiogenesis. In our approach, tyramine was first introduced into gelatin chains to provide enzymatic crosslinking points for gel formation after injection. Next, heparin, a polysaccharide with binding domains to many growth factors, was covalently linked to the tyramine-modified gelatin. Finally, vascular endothelial growth factor (VEGF) was incorporated into the gelatin derivative by binding with the heparin in the gelatin derivative, and an injectable gel with controlled VEGF release was formed by an enzymatic catalytic reaction with hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). The gelation time, mechanical properties and degradation of the gel was readily tailored by the gelatin concentration and the ratio of H2O2/HRP. Binding VEGF to heparin stabilizes this growth factor, protects it from denaturation and proteolytic degradation and subsequently prolongs the sustained release. An in vitro release study and bioactivity assay indicated that the VEGF was released in a sustained manner with high bioactivity for over 3 weeks. Furthermore, a chicken chorioallantoic membrane (CAM) assay and animal experiments were performed to evaluate in vivo bioactivity of the VEGF released from the hydrogels. After 5 days of incubation on CAM, the number of blood vessels surrounding the heparin-modified hydrogels was increased by 2.4-fold compared with that of the control group. Deeper and denser cell infiltration and angiogenesis in the heparin-modified gelatin/VEGF gels were observed compared to the controls after being subcutaneously injected in the dorsal side of the mice for 2 weeks. Interestingly, even without the incorporation of VEGF, the heparin-modified gelatin derivative still had the capability to induce angiogenesis to a certain degree. Our results suggest that the gelatin derivative/VEGF is an excellent injectable delivery system for induced angiogenesis of soft tissue regeneration., (Published by Elsevier Ltd.)

The primary request nowadays is for innovative and superior scaffold designs that mimic the characteristics of native tissue in cartilage tissue engineering. GelMA/Alginate (G/A) interpenetrating polymer network (IPN) has become a popular hydrogel material for tissue engineering because of its superior mechanical and biological properties. Here, to balance the properties, a hydrogel composed of G/A and covalent organic frameworks (COF) nanoparticles is specially designed. In this study, a hydrogel of GelMA/Alginate/COF (G/A/C) with improved properties such as pore size, swelling, mechanical strength, shear‐thinning behavior, and biocompatibility is produced. Furthermore, the G/A/C hydrogel facilitate the printing of complex three dimensional (3D) scaffolds. The test result demonstrates that the addition of COF up to 1% (w/w) enhances the porosity and decreases pore size (0.2 times), improves the compression strength (six times), and decreases the degradation ratio (0.05 times) and the swelling (0.3 times) compared to the G/A hydrogel sample. Besides, the cell viability test confirms the cell growth during the incubation and great biological behavior (more than 98%). The suitable performance of the G/A hydrogel containing 1% COF and its shape fidelity during the injection by 3D printer is confirmed. Nanocomposite IPN hydrogel based on G/A/C could be useful in tissue engineering applications. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non‐arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS‐related challenges, this study focuses on creating an injectable and tissue‐adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin‐modified hydrogel with photo‐crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin‐loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries. [ABSTRACT FROM AUTHOR]

A review of recent literature reveals a spurt in the publications using alginate dialdehyde (ADA)‐based hydrogels. This study evaluates the stability and characteristics of ADA solutions stored at different temperatures (4 & −20 °C; designated as ADA4°C & ADA−20°C) and durations (1, 3, and 6 months), and gives valuable insights into the shelf life, a parameter important in a clinical setting. ADA solutions were characterized for their viscosity, aldehyde content, molecular weight, and chemical structure before and after storage. The solution viscosities of ADA4°C showed a decreasing trend over 6 months while that of ADA‐20°C showed an increase. Compared to freshly prepared ADA, a significant reduction in aldehyde content, from 40.1±1.4 % to 37.1±1.01 %, was observed for ADA4°C stored for 6 months, but the aldehyde content was stable for ADA−20°C stored for the same period. Molecular weight remained stable (~6800 g/mol) irrespective of the storage temperatures. Injectable hydrogels were prepared by reacting the stored ADA solutions with 20 % aqueous solutions of gelatin. Hydrogels prepared with ADA stored at 4 °C for 6 months showed a significant increase in gelation time from 4.3±1.5 to 8.79±0.1 min and a decrease in degree of crosslinking from 54.3±1.4 % to 29.2±2.3 %. A decreasing trend was observed for properties such as water uptake (from 470 to 961 %) and tensile strength (from 348 to 282 kPa). Hydrogels made with ADA−20°C demonstrated better retention of physicochemical properties over time. In vitro studies revealed that the hydrogels showed a non‐cytotoxic response towards L929 cells irrespective of the storage conditions. LIVE/DEAD assay and F‐Actin staining revealed good cell proliferation on the hydrogels. In conclusion, retention of the properties of ADA in its aqueous solution requires careful control of storage temperatures. [ABSTRACT FROM AUTHOR]

Abstract Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non‐arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS‐related challenges, this study focuses on creating an injectable and tissue‐adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin‐modified hydrogel with photo‐crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin‐loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries.

The application of hydrogels in bone repair is limited due to their low mechanical strength. Simulating bone extracellular matrix, methylacrylylated gelatin (GelMA)/methylacrylylated hyaluronic acid (HAMA)/nano-hydroxyapatite(nHap) composite hydrogels were prepared by combining the double network strategy and composite of nHap in this study. The precursor solutions of the composite hydrogels were injectable due to their shear thinning property. The compressive elastic modulus of the composite hydrogel was significantly enhanced, the fracture strength of the composite hydrogel nearly reached 1 MPa, and the composite hydrogel retained its high water content at above 88%. The composite hydrogels possess good compatibility with BMSCS and have the potential to be used as injectable hydrogels for bone defect treatment. [ABSTRACT FROM AUTHOR]

Introduction: Biocompatible and biodegradable scaffolds based on natural polymers such as gelatin and chitosan (CS) provide suitable microenvironments in dental tissue engineering. In the present study, we report on the synthesis of injectable thermosensitive hydrogel (PNIPAAm-g-CS copolymer/gelatin hybrid hydrogel) for osteogenic differentiation of human dental pulp stem cells (hDPSCs). Methods: The CS-g-PNIPAAm was synthesized using the reaction of carboxyl terminated PNIPAAm with CS, which was then mixed with various amounts of gelatin solution in the presence of genipin as a chemical crosslinker to gain a homogenous solution. The chemical composition and microstructures of the fabricated hydrogels were confirmed by FT-IR and SEM analysis, respectively. To evaluate the mechanical properties (e.g., storage and loss modulus of the gels), the rheological analysis was considered. Calcium deposition and ALP activity of DPSCs were carried out using alizarin red staining and ALP test. While the live/dead assay was performed to study its toxicity, the real-time PCR was conducted to investigate the osteogenic differentiation of hDPSCs cultured on prepared hydrogels. Results: The hydrogels with higher gelatin incorporation showed a slightly looser network compared to the other ones. The hydrogel with less gelatin indicates a rather higher value of G', indicating a higher elasticity due to more crosslinking reaction of amine groups of CS via a covalent bond with genipin. All the hydrogels contained viable cells with negligible dead cells, indicating the high biocompatibility of the prepared hydrogels for hDPSCs. The quantitative results of alizarin red staining displayed a significant rise in calcium deposition in hDPSCs cultured on prepared hydrogels after 21 days. Further, hDPSCs cultured on hydrogel with more gelatin displayed the most ALP activity. The expression of late osteogenic genes such as OCN and BMP-2 were respectively 6 and 4 times higher on the hydrogel with more gelatin than the control group after 21 days. Conclusion: The prepared PNIPAAm-g-CS copolymer/gelatin hybrid hydrogel presented great features (e.g., porous structure, suitable rheological behavior, and improved cell viability), and resulted in osteogenic differentiation necessary for dental tissue engineering.

Enzymatically catalyzed cross-linking is a hydrogel fabrication method that generally is considered to have lower cytotoxicity than traditional chemical cross-linking methods. In order to optimize the properties of injectable hydrogels and expand their applications, an enzyme-catalyzed cross-linked injectable hydrogel was designed. The tyramine-modified gelatin (G-T) was formed into a stable injectable hydrogel by the combination of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) catalysis. 1H NMR spectroscopy was used to demonstrate the successful modification of gelatin by tyramine. The surface morphology of the prepared hydrogels was characterized jointly by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Rheological tests demonstrated the tunable mechanical strength, formation kinetics, shear thinning and good self-recovery properties of the hydrogels. In addition, the hydrogels can be formed into various shapes by injection. The hydrogel network structure is complex and interlaced, as such it is suitable to encapsulate drugs for controlled release. The drug release from the prepared hydrogels followed the Peppas–Sahlin model and belonged to Fickian diffusion. This study constructed injectable hydrogels through the enzyme-catalyzed cross-linking of modified gelatin and applied the hydrogels for drug release, which is expected to expand the application in biomedical fields. This work reports an enzyme-catalyzed cross-linking of injectable hydrogels. Tyramine-modified gelatin is used as the raw material, and horseradish peroxidase and H2O2 are added to catalyze the cross-linking to form an injectable hydrogel. The hydrogel can be used for drug release which will broaden the application of hydrogels in biomedical fields. [ABSTRACT FROM AUTHOR]

Overproduction of reactive oxygen species is one of the important reasons of non-healing wounds, such as diabetic wounds. Melatonin is well known as an antioxidant, while the poor solubility limits its use in many areas. In this study, the solubility of melatonin was improved by introducing γ-cyclodextrin to form the composite named MT-γ-CD through ultrasonic process. During this process, the molar ratio of melatonin and γ-cyclodextrin was 2:1, the temperature was set at 30 ℃, and the ultrasonic time was 40 min. The MT-γ-CD showed good antioxidant property in vitro with high free radical scavenging efficiency over 90%. Besides, an injectable self-healing hydrogel was prepared to load with MT-γ-CD to form the wound dressing, here, sodium carboxymethylated cellulose was oxidized to introduce aldehyde groups that could form Schiff base with amino groups in gelatin. This dressing with good biocompatibility could be injected into irregular wounds, suppress the level of reactive oxygen species, and accelerate wound healing of diabetic rats in vivo. Therefore, it has great potential to provide a new treatment strategy for diabetic wounds. [ABSTRACT FROM AUTHOR]

Introduction: Biocompatible and biodegradable scaffolds based on natural polymers such as gelatin and chitosan (CS) provide suitable microenvironments in dental tissue engineering. In the present study, we report on the synthesis of injectable thermosensitive hydrogel (PNIPAAmg-CS copolymer/gelatin hybrid hydrogel) for osteogenic differentiation of human dental pulp stem cells (hDPSCs). Methods: The CS-g-PNIPAAm was synthesized using the reaction of carboxyl terminated PNIPAAm with CS, which was then mixed with various amounts of gelatin solution in the presence of genipin as a chemical crosslinker to gain a homogenous solution. The chemical composition and microstructures of the fabricated hydrogels were confirmed by FT-IR and SEM analysis, respectively. To evaluate the mechanical properties (e.g., storage and loss modulus of the gels), the rheological analysis was considered. Calcium deposition and ALP activity of DPSCs were carried out using alizarin red staining and ALP test. While the live/dead assay was performed to study its toxicity, the real-time PCR was conducted to investigate the osteogenic differentiation of hDPSCs cultured on prepared hydrogels. Results: The hydrogels with higher gelatin incorporation showed a slightly looser network compared to the other ones. The hydrogel with less gelatin indicates a rather higher value of G', indicating a higher elasticity due to more crosslinking reaction of amine groups of CS via a covalent bond with genipin. All the hydrogels contained viable cells with negligible dead cells, indicating the high biocompatibility of the prepared hydrogels for hDPSCs. The quantitative results of alizarin red staining displayed a significant rise in calcium deposition in hDPSCs cultured on prepared hydrogels after 21 days. Further, hDPSCs cultured on hydrogel with more gelatin displayed the most ALP activity. The expression of late osteogenic genes such as OCN and BMP-2 were respectively 6 and 4 times higher on the hydrogel with more gelatin than the control group after 21 days. Conclusion: The prepared PNIPAAm-g-CS copolymer/gelatin hybrid hydrogel presented great features (e.g., porous structure, suitable rheological behavior, and improved cell viability), and resulted in osteogenic differentiation necessary for dental tissue engineering. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hydrogel is a three-dimensional structure that has the potential to absorb and retain water within the mesh of its porous network structure. Currently hydrogels made from natural biopolymers are preferred in the discipline of biomedical applications because of their blood compatibility, adhesion of platelets and protein binding, ease of administration and delivery of ingredients to the place of action. OBJECTIVE: The aim of this work was to prepare a hydrogel from natural biopolymers and evaluate its blood compatibility, swelling nature, prolonged degradation and morphological features in order to further recommend its clinical use. METHODS: To prepare hydrogels, different combinations of gelatin, dialyzed SF, curcumin and N, N methylene bisacrylamide (MBA) were evenly mixed on a magnetic stirrer. After an hour of the gelation process it was kept in a refrigerator at 4 °C. For the characterization and biocompatibility studies of hydrogel, the swelling test and biodegradation analysis, SEM, FTIR, in vitro coagulation tests, total serum albumin and cholesterol level analysis were applied. RESULTS: Injectable hydrogels were successfully made with significantly correlated combinations of polymers. The analysis of physiochemical biocompatibility studies and morphological characterization were done effectively. CONCLUSION: The results of the study indicate that hydrogels made from natural biopolymers are a potential source and suitable matrices with excellent biocompatible nature acting as a useful device in delivering drugs. [ABSTRACT FROM AUTHOR]

Inspired by the commonly used creams in dermatology, the present study introduced a simple method to prepare a granular hydrogel that could be applied to the whole wound area via spread to promote wound healing. Gelatin microspheres were fabricated and densely stacked, followed by adsorbing dopamine and Zn2+ solution. Dopamine polymerised in-situ to form gelatin/polydopamine (PDA)/Zn2+ composite microspheres, which were self-assembled to form a granular hydrogel. Zn2+ accelerated dopamine polymerization. PDA formed Schiff base and hydrogen bond with gelatin, realizing the assembly among the composite microspheres. The granular hydrogel exhibited bulk feature, shear-thinning and self-healing properties, which was injectable and spreadable like creams. Zn2+ in hydrogel showed sustained and stable release within 7 d. The granular hydrogel was applied to wound and significantly promoted wound healing, shortening the healing time within 10 days. The present injectable granular hydrogel thus showed convenient and advanced features towards surgical wound treatment. [ABSTRACT FROM AUTHOR]

Oxidative stress caused by the overexpression of reactive oxygen species (ROS) plays an important role in the pathogenesis of traumatic brain injury (TBI). Accumulation of ROS can lead to cell death, neurodegeneration, and neurological deficit. Therefore, the design and application of functional materials with ROS scavenging ability is of great significance for neural repair. Herein, an injectable and antioxidant hydrogel was developed for TBI treatment based on the Schiff base reaction of gallic acid-conjugated gelatin (GGA) and oxidized dextran (Odex). The resulting GGA/Odex hydrogel could effectively scavenge DPPH and ABTS radicals, as well as protect cells from the oxidative damage in vitro. Moreover, GGA/Odex hydrogel possessed well biocompatible features. In a moderate TBI mouse model, in situ implantation of GGA 6 Odex hydrogel efficiently facilitated neurogenesis and promoted the motor, learning and memory abilities. Also, this composite hydrogel suppressed oxidative stress and inflammation via the activation of Nrf2/HO-1 pathway and the regulating of inflammatory factors secretion and macrophage/microglia polarization. Therefore, this injectable and ROS-scavenging GGA 6 Odex hydrogel is a promising biomaterial for tissue regenerative medicine, including TBI and other tissue repair relevant to raised ROS circumstance. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Cartilage defects pose a significant burden on medical treatment, leading to an urgent need to develop regenerative medicine approaches for cartilage repair, such as stem cell therapy. However, the direct injection of stem cells can result in insufficient delivery or inaccurate differentiation. Hence, it is necessary to choose appropriate stem cell delivery scaffolds with high biocompatibility, injectability and chondral differentiation induction ability for cartilage regeneration. Methods: In this study, the photocrosslinked gelatin methacrylate (GelMA) hydrogel with high cell affinity and plasticity was selected and strengthened by incorporating methacrylic anhydride-modified poly(amidoamine) (PAMAM-MA) to fabricate an adipose-derived stromal/stem cells (ASCs) delivery scaffold for cartilage repair. The physiochemical properties of the GelMA/PAMAM-MA hydrogel, including the internal structure, stability and mechanical properties, were tested. Then, ASCs were encapsulated into the hydrogels to determine the in vitro and in vivo chondrogenic differentiation induction abilities of the GelMA/PAMAM-MA hydrogel. Results: Compared with the GelMA hydrogel, the GelMA/PAMAM-MA hydrogel exhibited more uniform structure, stability and mechanical properties. Moreover, on the basis of good biocompatibility, the hybrid hydrogel was proven to exert a sufficient ability to promote cartilage regeneration by in vitro three-dimensional (3D) culture of rASCs and in vivo articular cartilage defect repair. Conclusions: The injectable photocrosslinked GelMA/PAMAM-MA hydrogel was proven to be a capable stem cell carrier for cartilage repair and provides new insight into the design strategy of stem cell delivery scaffolds. [ABSTRACT FROM AUTHOR]

The irregular shape and depth of wounds could be the major hurdles in wound healing for the common three-dimensional foam, sheet, or film treatment design. The injectable hydrogel is a splendid alternate technique to enhance healing efficiency post-implantation via injectable or 3D-bioprinting technologies. The authentic combination of natural and synthetic polymers could potentially enhance the injectability and biocompatibility properties. Thus, the purpose of this study was to characterise a hybrid gelatin–PVA hydrogel crosslinked with genipin (GNP; natural crosslinker). In brief, gelatin (GE) and PVA were prepared in various concentrations (w/v): GE, GPVA3 (3% PVA), and GPVA5 (5% PVA), followed by a 0.1% (w/v) genipin (GNP) crosslink, to achieve polymerisation in three minutes. The physicochemical and biocompatibility properties were further evaluated. GPVA3_GNP and GPVA5_GNP with GNP demonstrated excellent physicochemical properties compared to GE_GNP and non-crosslinked hydrogels. GPVA5_GNP significantly displayed the optimum swelling ratio (621.1 ± 93.18%) and excellent hydrophilicity (38.51 ± 2.58°). In addition, GPVA5_GNP showed an optimum biodegradation rate (0.02 ± 0.005 mg/h) and the highest mechanical strength with the highest compression modulus (2.14 ± 0.06 MPa). In addition, the surface and cross-sectional view for scanning electron microscopy (SEM) displayed that all of the GPVA hydrogels have optimum average pore sizes (100–199 μm) with interconnected pores. There were no substantial changes in chemical analysis, including FTIR, XRD, and EDX, after PVA and GNP intervention. Furthermore, GPVA hydrogels influenced the cell biocompatibility, which successfully indicated >85% of cell viability. In conclusion, gelatin–PVA hydrogels crosslinked with GNP were proven to have excellent physicochemical, mechanical, and biocompatibility properties, as required for potential bioinks for chronic wound healing. [ABSTRACT FROM AUTHOR]

The application of hydrogels in bone repair is limited due to their low mechanical strength. Simulating bone extracellular matrix, methylacrylylated gelatin (GelMA)/methylacrylylated hyaluronic acid (HAMA)/nano-hydroxyapatite(nHap) composite hydrogels were prepared by combining the double network strategy and composite of nHap in this study. The precursor solutions of the composite hydrogels were injectable due to their shear thinning property. The compressive elastic modulus of the composite hydrogel was significantly enhanced, the fracture strength of the composite hydrogel nearly reached 1 MPa, and the composite hydrogel retained its high water content at above 88%. The composite hydrogels possess good compatibility with BMSCS and have the potential to be used as injectable hydrogels for bone defect treatment.

The efficacy of myocardial regeneration strategies for myocardial infarction (MI) is significantly compromised by the complex structure and microenvironment of the myocardium. Although tissue engineering strategies based on cell therapy and/or pro-angiogenesis can somewhat improve cardiac function, the lack of proper myocardial materials that can withstand sustained deformability and adaptable mechanical properties severely affects myocardial wall integrity, systolic-diastolic cycles, and regeneration. Herein, we developed an integrated single "all-in-one" in situ dual crosslinking conductive hydrogel with favorable treatment properties termed as MaHA/B-G-SH/Fe3+ by ionic interactions and chemical covalency based on modified hyaluronic acid (HA), gelatin (G), and Fe3+. The resulting dual crosslinking dynamic hydrogel not only provides self-healing and mechanical properties adapted to the myocardial systolic-diastolic cycle with simultaneous electrical signal transmission to fibrous islands and normal tissue, but also leads to significant increase of the myocardial wall thickness very close to that of normal myocardium upon one single injection with complete degradation within 28 days. Notably, the hydrogel covalently conjugated with a tailored peptide sequence of GGR-KLT and encapsulated with bone mesenchymal stem cells (BMSCs) was further used for in situ injection in a rat MI model, which exhibited (i) efficient inhibition of excessive matrix degradation dependent on early MMP-2 expression, (ii) triggered on-demand release of KLT for at least 14 days and significant promotion of angiogenesis, and (iii) synergistic BMSCs considerably enhanced myocardial regeneration within 28 days. Taken together, the dual crosslinking conductive hydrogel-mediated synergistic peptide and cell therapy provides comprehensive recovery and regeneration of the structure and function of the injured myocardium, thus demonstrating great potential for clinical translations. [Display omitted] • The dual cross-linked hydrogel has the ability to support myocardial systole-diastole. • The GGR exhibited inhibition of excessive degradation of the ECM by early MMPs. • The GGR-KLT exhibited on-demand release of KLT for promoted angiogenesis. • The hydrogel-mediated integrated therapy provides efficient regeneration for MI. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. This study aimed to compare the effect of sunitinib-loaded poly (glycerol sebacate) (PGS)/gelatin nanoparticles doped in an injectable hydrogel with bevacizumab as a standard treatment of DR. The shear-sensitive hydrogel was prepared based on tragacanthic acid (TA) cross-linked with sodium acetate. DR was induced in rats by streptozotocin (STZ), and the animals were injected intravitreally a single dose of 20 µL sunitinib solution in three different concentrations (12.5, 25, and 50 µg/mL), sunitinib-loaded nanoparticles in hydrogel (413 µg/mL) and bevacizumab solution (6.25 mg/mL). The efficacy of the treatments was studied by histological and immunohisitological tests, angiogenesis, and optical coherence tomography (OCT). Vascular endothelial growth factor (VEGF) concentration was measured in the retina. The results revealed that 20 µL of sunitinib with the concentration of 25 µg/mL was effective in DR without any disruption in the retina or any other side effects. This dose was considered the therapeutic dose for nanoparticles. Sunitinib loaded PGS/gelatin nanoparticles that were incorporated in the injectable hydrogel were as effective as bevacizumab in controlling DR. Although sunitinib solution reduced VEGF production and neovascularization in the retina compared to the negative control group, it was not as suitable as the nanoparticles. TA-based hydrogel showed no toxicity on the normal retina, and the angiography and histologic studies confirmed the VEGF results.' Sunitinib nanoparticles doped in TA hydrogel may be an appropriate substitution of bevacizumab in the treatment of DR. [ABSTRACT FROM AUTHOR]

The irregular shape and depth of wounds could be the major hurdles in wound healing for the common three-dimensional foam, sheet, or film treatment design. The injectable hydrogel is a splendid alternate technique to enhance healing efficiency post-implantation via injectable or 3D-bioprinting technologies. The authentic combination of natural and synthetic polymers could potentially enhance the injectability and biocompatibility properties. Thus, the purpose of this study was to characterise a hybrid gelatin–PVA hydrogel crosslinked with genipin (GNP; natural crosslinker). In brief, gelatin (GE) and PVA were prepared in various concentrations (w/v): GE, GPVA3 (3% PVA), and GPVA5 (5% PVA), followed by a 0.1% (w/v) genipin (GNP) crosslink, to achieve polymerisation in three minutes. The physicochemical and biocompatibility properties were further evaluated. GPVA3_GNP and GPVA5_GNP with GNP demonstrated excellent physicochemical properties compared to GE_GNP and non-crosslinked hydrogels. GPVA5_GNP significantly displayed the optimum swelling ratio (621.1 ± 93.18%) and excellent hydrophilicity (38.51 ± 2.58°). In addition, GPVA5_GNP showed an optimum biodegradation rate (0.02 ± 0.005 mg/h) and the highest mechanical strength with the highest compression modulus (2.14 ± 0.06 MPa). In addition, the surface and cross-sectional view for scanning electron microscopy (SEM) displayed that all of the GPVA hydrogels have optimum average pore sizes (100–199 μm) with interconnected pores. There were no substantial changes in chemical analysis, including FTIR, XRD, and EDX, after PVA and GNP intervention. Furthermore, GPVA hydrogels influenced the cell biocompatibility, which successfully indicated >85% of cell viability. In conclusion, gelatin–PVA hydrogels crosslinked with GNP were proven to have excellent physicochemical, mechanical, and biocompatibility properties, as required for potential bioinks for chronic wound healing.

• Injectable hydrogel of E. prolifera polysaccharide & gelatin derivatives is prepared. • Hydrogel synthesis is inspired by siderophores and biocatalysis for fast gelation. • Hydrogel possesses self-healing, tissue adhesiveness and proper mechanical properties. • Hydrogel can promote all four phases of chronic diabetic wound healing. • Insights into chronic diabetic wound therapy in clinical applications are provided. Given that chronic diabetic wounds are difficult to cure because of disruptions in the four healing phases (hemostasis, immune regulation, cell proliferation, and tissue regeneration), wound dressings promoting all of these phases and thus accelerating diabetic wound healing are highly desirable. To address this need, inspired by siderophore-Fe3+ chelation and horseradish peroxidase (HRP) catalysis, we synthesized a tyramine-modified Enteromorpha prolifera polysaccharide and dopamine-modified gelatin and used them to fabricate an injectable hydrogel (PG-Fe) featuring interpenetrating polymer networks facilitated by catecholate/carboxylate-Fe3+ coordination bonding and HRP-mediated covalent bonding between phenolic groups. PG-Fe exhibited good injectability, rapid gelation (11.5 s), suitable mechanical properties, enhanced tissue adhesiveness (50.5 kPa), and rapid self-healing (60 s) because of its intrinsic moieties and introduced modifications. Furthermore, it exhibited enhanced antioxidant, anti-inflammatory, cell adhesion, and migration effects. Consequently, PG-Fe simultaneously addressed all four wound healing phases, thereby shortening the closure time of normal and chronic diabetic wounds to 21 days. Following application, PG-Fe could be decomposed using a desferrioxamine solution and easily removed. Taken together, our study provides a novel strategy for fabricating injectable hydrogels that exhibit desirable physicochemical properties and enhanced biological functions to accelerate all phases of chronic diabetic wound healing. [ABSTRACT FROM AUTHOR]

BACKGROUND: Due to no vascular structure or nerve tissue, cartilage tissue lacks the intrinsic ability of self-repair and regeneration. Therefore, the repair of cartilage defect in clinic remains a challenge. OBJECTIVE: To prepare a thermo-sensitive injectable bioactive hydrogel used for cartilage tissue engineering. METHODS: Agarose/gelatin/hyaluronic acid hydrogel was prepared by mixing 0.4% agarose, 10% gelatin and 10 g/L hyaluronic acid solution. Then 0, 10, 20, and 30 g/L cartilage extracellular matrix particles were added into the hydrogel respectively to prepare four kinds of thermo-sensitive injectable bioactive hydrogels, for further scanning electron microscope, transmission electron microscope, equilibrium swelling ratio, biomechanical strength and degradation rate. The thermo-sensitive injectable bioactive hydrogel containing 20 g/L cartilage extracellular matrix was co-cultured with chondrocyte-bone marrow mesenchymal stem cells for 1, 3, and 7 days, and the cytocompatibility was assessed by live/dead fluorescence double staining. RESULTS AND CONCLUSION: (1) Scanning electron microscope showed that all four hydrogels had good three-dimensional grid structure and large pore size. Transmission electron microscope showed that extracellular matrix particles were evenly distributed in the hydrogels, and the particle size was mainly in the range of 50-200 nm. (2) With the extracellular matrix particle concentration increasing, the equilibrium swelling rate of the hydrogel was decreased. (3) The degradation rate in vitro in the four groups of hydrogels containing 0, 10, 20, and 30 g/L extracellular matrix particles immersed in PBS for 4 weeks was 42.32%, 67.36%, 89.05% and 99.47%, respectively. (4) When the concentration of extracellular matrix particles was added at 0-20 g/L, the biomechanical strength of the hydrogel was gradually increased. (5) Within 7 days after culture, chondrocytes-bone marrow mesenchymal stem cells were uniformly distributed and grew in the hydrogel and proliferated continuously, with the cell survival rate of above 90%. (6) These results showed that the agarose/gelatin/hyaluronic acid hydrogel modified with extracellular matrix particles is a good medical biomaterial that can be used for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract Tissue sealants are used for hemorrhage control which is imperative in many surgical procedures. It is a highly challenging task to obtain the ideal tissue sealant. Only a few commercially tissue sealants are available to be used for internal tissue or organ hemorrhage control. This study introduced two in situ injectable hydrogels for hemorrhage control: self-crosslinking gelatin (sc-G) hydrogel and hyaluronic acid/gelatin (HA/G) hydrogel. They were prepared on the tissue surface in situ and characterized by rheological analysis, stability, cytotoxicity, and bursting strength test. The hemostatic ability of the hydrogels was evaluated in a liver-bleeding rat model. The sc-G and HA/G hydrogels gelled around 90 s and 50 s, respectively. They were preferable for cell attachment and proliferation. The bursting strengths of both hydrogels exceeded that of fibrin glue. The hemostatic ability of HA/G hydrogel was better than that of sc-G hydrogel, and was same as that of fibrin glue. The HA/G hydrogel could be used as a tissue sealant for hemorrhage control in clinic. Highlights • This study introduced an in situ injectable hyaluronic acid/gelatin hydrogel, which was prepared by chemically crosslinking hyaluronic acid and gelatin with EDC/NHS. • The hydrogel had the short gelatin time, good cytocompatibility, strong bursting strength and well hemostatic ability. • The hemostatic ability of HA/G hydrogel was same as that of fibrin glue. It suggested that the hydrogel could be a tissue sealant for hemorrhage control in clinic. [ABSTRACT FROM AUTHOR]

[Display omitted] • A printable shear-thinning GelMA based nanocomposite for soft tissue engineering. • Formation of a layer of polydopamine on the surface of graphene oxide nanoplates. • Visible light was used instead of UV light to crosslink the GelMA hydrogel. • The hydrogel showed appropriate printability and shear thinning behavior. The use of bio ink materials for fabricating scaffolds is the best option to replace aggressive surgery. This study aims to formulate an injectable hydrogel with suitable structural, mechanical, and rheological properties for tissue engineering applications. In this respect, gelatin methacrylate (GelMA) nanocomposites with different amounts of the modified graphene oxide nanoplates (0.25, 0.5, 0.75, and 1 wt%) were fabricated. The effect of the nanoplates on the structural, degradability, mechanical, rheological, and biological properties of the nanocomposites were evaluated. The results revealed that the functionalization of graphene oxide with dopamine (GOPD) resulted in the formation of a layer of polydopamine on the surface of the nanoplates, which developed the interaction of graphene oxide with GelMA chains. Adding GOPD to GelMA from 0 to 1 wt% decreased the water absorption (0.3 times) and its weight loss percentage (0.2 times). The addition of 0.5 wt% of GOPD to GelMA improved the compressive strength (7.5 times) and compressive modulus (7 times) compared to the GelMA hydrogel. Also, a similar amount of GOPD developed the thin shear properties of GelMA by three logarithmic units. Besides, the addition of the modified graphene oxide nanoplates to GelMA enhanced cell viability (93.26%) after 72 h of cell seeding. The proper behavior of the GelMA hydrogel with 0.5% GOPD , and its stability during the 3D printing process was confirmed. Accordingly, the injectable GelMA hydrogel containing dopamine-modified graphene oxide could be a proper candidate for tissue engineering expenditures. [ABSTRACT FROM AUTHOR]

Diabetic wounds are chronic wounds that are currently affecting many patient's quality of life. These wounds are challenging because of the impaired healing cycle and harsh environment. In this study in situ gelling hydrogels based on oxidized carboxymethyl cellulose (OCMC) and gelatin (Gel) were used to hasten the healing rate due to their ease of application. The suggested system in this work is synthesized from entirely natural renewable biomaterials to not only achieve the best biocompatibility and biodegradability but also to develop a sustainable product. The rheological studies showed that the hydrogel is turned into a gel after about 30 s of the mixing process. Moreover, the hydrogel can absorb about ten times its weight, keeping the wound hydrated. In vitro biological investigations indicated optimal biocompatibility, antibacterial, and antioxidant activity for faster tissue regeneration. This product was tested in vivo on normal rats and diabetic mice models to treat full-thickness incisional wounds. Results showed that the OCMC-Gel hydrogel is able to hasten the healing rate in both non-diabetic and diabetic wounds. Pathological examinations of the regenerated skin tissue revealed that the OCMC-Gel treated groups developed much more than the control group. [Display omitted] [ABSTRACT FROM AUTHOR]

In this work, we developed a novel enzymatically cross-linked injectable hydrogel composed of carboxymethyl cellulose (CMC), sulfated carboxymethyl cellulose (sCMC) and gelatin for delivery of infrapatellar fat pad derived MSCs and articular chondrocytes to a cartilage defect site while enabling TGF-β1 mediated chondrogenesis. The sCMC component in the hydrogel served the purpose of mimicking heparan sulfate and thus enabled strong binding with TGF-β1 and its consequential long term presentation to the encapsulated cells. We demonstrated that amongst CMC/sCMC/gelatin hydrogels cross-linked with 1 and 2 mM H 2 O 2 , the latter demonstrated significantly higher compressive modulus and supported better in vitro cartilage formation. Thereafter, we explored the utility of this system to present TGF-β1 to encapsulated cells for prolonged time period. It was observed that these hydrogels could sequester >90% of encapsulated TGF-β1 for at least 4 weeks. The encapsulated TGF-β1 was shown to be bioactive and supported significantly better cell survival over control hydrogels. Further, the TGF loaded hydrogels demonstrated good sulfated GAG and collagen deposition which was higher than control hydrogels and comparable to those treated with soluble TGF-β1 through media. Interestingly, incorporation of TGF-β1 in hydrogels not only enhanced the expression and deposition of hyaline cartilage markers, but it also significantly reduced the deposition of fibrocartilage and hypertrophy markers. Overall, it was concluded that TGF-β1 immobilized CMC/sCMC/gelatin injectable hydrogels encapsulated with IFP MSCs and ACs present a promising, cost effective and easily translatable strategy for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

• The hydrogel can kill bacteria by sustainably releasing Ag+ with its degradation. • It alleviates the host inflammatory response mediated bystander damage. • The designed hydrogel are ideal for anti-CXCL1 delivery. • It combines antibacterial and immunotherapy in infectious endophthalmitis. • This work may provide a new idea to treat endophthalmitis in clinical practice. Bacterial endophthalmitis is a serious ocular infection and frequently results in vision loss or even blindness. Most of the present treatment methods are mainly embodied in strengthening the bactericidal effect, whereas the bacteria induced vigorous host immune response often leads to irreversible damage to eye tissue. Herein, we report an injectable hydrogel to treat endophthalmitis by killing invading bacteria and regulating ocular immunity. The designed hydrogel was formed by dynamic coordination crosslinking of sulfhydryl modified gelatin and silver ion while embedding the anti-CXCL1 antibody evenly. The injectable hydrogel can not only kill bacteria by releasing silver ions with its degradation, but also alleviate the bacteria-triggered excessive immune response via releasing anti-CXCL1 antibody to neutralize chemokine CXCL1, thus avoiding the host inflammatory response mediated bystander damage. Both in vitro and in vivo experiments showed that it has excellent ability against bacteria and immunomodulatory performance, preserving more integral retinal architecture and promoting visual recovery. This work may open up new avenues for combining antibacterial and immunotherapy in infectious endophthalmitis. [ABSTRACT FROM AUTHOR]

Use of injectable hydrogels attract attention in the regeneration of dental pulp due to their ability to fill non-uniform voids such as pulp cavities. Here, gelatin methacrylate/thiolated pectin hydrogels (GelMA/PecTH) carrying electrospun core/shell fibers of melatonin (Mel)-polymethylmethacrylate (PMMA)/Tideglusib (Td)-silk fibroin (SF) were designed as an injectable hydrogel for vital pulp regeneration, through prolonged release of Td and Mel to induce proliferation and odontoblastic differentiation of dental pulp stem cells (DPSC). H NMR and FTIR confirmed methacrylation of Gel and thiolation of Pec. Addition of PMMA/SF increased degradation and water retention capacities of GelMA/PecTH. Rheological analyses and syringe tests proved the injectability of the hydrogel systems. Release studies indicated that Td and Mel were released from the fibers inside the hydrogels sequentially due to their specific locations. This release pattern from the hydrogels resulted in DPSC proliferation and odontogenic differentiation in vitro. Gene expression studies showed that the upregulation of DMP1, DSPP, and Axin-2 genes was promoted by GelMA/PecTH carrying PMMA/SF loaded with Mel (50 µg/mL) and Td (200 nM), respectively. Our results suggest that this hydrogel system holds promise for use in the regeneration of pulp tissue. [Display omitted] • Injectable GelMA/PecTH-based hydrogels were prepared for vital pulp regeneration. • Electrospun core/shell PMMA/SF fibers were incorporated into the hydrogels. • SF shell was loaded with Tideglusib (Td) to primarily promote pulp regeneration. • PMMA core was loaded with Melatonin (Mel) to induce odontogenic differentiation. • Fiber+hydrogel systems enhanced proliferation and differentiation of DPSC in vitro. [ABSTRACT FROM AUTHOR]

Gelatin hydrogels have recently attracted much attention for tissue regeneration because of their biocompatibility. In this study, we introduce poly-ethylene glycol (PEG)-grafted gelatin containing tyramine moieties which have been utilized for in situ enzyme-mediated hydrogel preparation. The hydrogel can be used to load nanoparticles of biphasic calcium phosphate, a mixture of hydroxyapatite and β-tricalcium phosphate, and forming injectable bio-composites. Proton nuclear magnetic resonance (H NMR) spectra indicated that tyramine-functionalized polyethylene glycol-nitrophenyl carbonate ester was conjugated to the gelatin. The hydrogel composite was rapidly formed in situ (within a few seconds) in the presence of horseradish peroxidase and hydrogen peroxide. In vitro experiments with bio-mineralization on the hydrogel composite surfaces was well-observed after 2 weeks soaking in simulated body fluid solution. The obtained results indicated that the hydrogel composite could be a potential injectable material for bone regeneration. [ABSTRACT FROM AUTHOR]

Poly( l -lactic acid) (PLLA) microfibers were surface functionalized by graft photopolymerization of 2-hydroxyethyl methacrylate (HEMA) onto the fiber surface. Grafted fibers were easily dispersed in enzymatically gelling tyramine-substituted gelatin, forming a homogeneous dispersion without hindering subsequent gelatin crosslinking. The obtained injectable hydrogels showed improved mechanical properties compared to analogues based on non-modified fibers. The composite with 1% (w/v) of surface modified fibers had a three-fold higher shear storage modulus (535.2 ± 90 Pa) than pure gelatin (184.9 ± 32 Pa) while no significant increase was observed in the case of non-grafted fiber composites. Moreover, PHEMA grafting on PLLA fibers did not compromise cell viability and proliferation within the hydrogel. The new injectable hydrogels offer improved potential as substrates for the regeneration of soft tissues. [ABSTRACT FROM AUTHOR]