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The typical symptoms of arthritis are inflammation and lubrication deficiency in joints, which increase wear of articular cartilage along with pain of patients. In the present study, one kind of novel macromolecular/microsphere-based injectable hydrogels (CMC-ODex NPs) with dual functionalities of drug release and lubrication, was fabricated via dynamic Schiff base crosslinking network between carboxymethyl chitosan (CMC) and oxidation dextran nanoparticles (ODex NPs). The CMC-ODex NPs hydrogels exhibited typical viscosity-thinning phenomenon at wide range of shear rates and obvious gel-sol transition feature at specific strain. As a result, CMC-ODex NPs hydrogels presented low friction coefficient at the sliding interface of bovine articular cartilages, resulting from the boundary lubrication of hydrogel and the rolling friction effect of ODex NPs. Furthermore, the anti-inflammatory drug (dexamethasone, DXM) encapsulated in ODex NPs exhibited sustainable drug release behavior during the dynamic shearing process, which making CMC-ODex NPs hydrogels possessed good and stable anti-inflammatory effect. CMC-ODex NPs hydrogels was prepared without utilizing any toxic agents, thus demonstrated excellent cytocompatibility. Our experimental results reveal the CMC-ODex NPs hydrogels is promising to be used as functional lubricant for inhibiting the development of arthritis. [Display omitted] • A novel injectable hydrogels (CMC-ODex NPs) with dual functionalities of drug release and water lubrication is prepared. • CMC-ODex NPs hydrogels was formed by applying dynamic Schiff base reaction between drugs-loaded ODex NPs and CMC. • The dynamic crosslinking network of CMC-ODex NPs hydrogels makes it present typical gel-sol transition behavior under shearing. • CMC-ODex NPs hydrogels exhibit good lubrication performance, sustained drug release and good biocompatibility. [ABSTRACT FROM AUTHOR]

Currently, hydrogels are widely studied for wound dressings. However, wound healing is often hindered by bacterial infection. In this study, in situ cross-linked carboxymethyl chitosan (CMCS)/oxidized dextran (OD)/poly-γ-glutamic acid (γ-PGA) (COP) hydrogel was prepared for antimicrobial and hemostasis of diffuse wounds. In the COP hydrogel, γ-PGA was able to drain the surface moisture of the wound to enhance the surface adhesion. Moreover, γ-PGA could concentrate blood by absorbing plasma, and CMCS could electrostatically adsorb negative RBCs. The antibacterial properties of CMCS and OD endowed the COP hydrogel with certain antibacterial effects. In the inhibition zone experiment, an obvious inhibition zone appeared around the COP hydrogel. In vivo studies showed that the COP hydrogel significantly inhibited bacterial growth and promoted wound healing. In the rat tail diffuse hemorrhage wound model, the COP hydrogel showed superior hemostasis ability. Therefore, the multifunctional COP hydrogel is expected to find different applications in wound hemostasis and healing. [ABSTRACT FROM AUTHOR]

Development of an injectable hemostatic for treating noncompressible or irregularly shaped bleeding wounds remains a pressing medical need. Herein, we report an injectable thermogelling chitosan/glycerophosphate formulation that enhances gel-forming capacity and wet tissue adherence by incorporation of dihydrocaffeic acid (DHCA). This was found to decrease gelation time by >2 times around 37 °C while increasing hydrogel internal network structure, with its tissue adhesive strength >2 times greater than that of the non-composite hydrogel or previously reported. The thermosensitive hydrogels significantly reduce whole blood coagulation time in vitro and both hemostasis time and blood loss in vivo using rat hepatic hemorrhage and tail amputation models. These improvements are biocompatible, without adversely affecting cell viability, blood components, biodegradability, or introducing notable inflammation, thus enabling injury healing. Moreover, our results displayed the potential of a facile approach to enhance thermogelling and bioadhesion of chitosan-based hydrogels via noncovalent supramolecular mechanisms. [ABSTRACT FROM AUTHOR]

With the development of minimally invasive orthopedics, injectable materials for bone repair are attracted more attention, especially for those wound with a small external mouth and sizeable internal cavity. In this work, the hydrogel with features of thermo-responsiveness, degradability and injectability was designed and fabricated. The hydrogel, named as FHCS, is composed of Pluronic F-127 (F127) loaded with carboxymethyl chitosan/sodium alginate nanoparticles (nCS) and nanohydroxyapatite (nHA). The hydrogel FHCS was non-toxic and good hemocompatible. It can enhance the ALP activity and extracellular matrix calcification of MC3T3-E1 due to the chitosan-based nanoparticle components (nCS). Moreover, FHCS-5 (containing 5 mg/mL nCS) showed relative high expression of osteogenic genes and protein markers. Osteal regeneration was observed treated by FHCS-5 hydrogel in a critical-size rat calvarial bone defect model. CT scanning showed that the whole defect was basically covered by new bone after FHCS-5 hydrogel. The results of H&E staining and Masson's trichrome staining on histological sections further confirmed that FHCS-5 hydrogel promoted new osteal formation and maturation, which up regulated the osteogenic related genes and proteins of ALP, OCN, OPN through BMP/Smad signaling pathway. Hence, this study suggests that FHCS-5 hydrogels have a promising application for non-loading bone regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

In orthopedic practice, accommodating irregular defects caused by trauma or surgery with traditional preformed bone graft substitutes is often challenging. As a result, injectable hydrogels with seed cells have garnered significant interest in bone repair due to their adaptability and minimally invasive properties. However, they cannot simultaneously achieve injectability and mechanical properties, providing a biophysical and biochemical environment for cell support. In this study, a novel injectable hydrogel system (OA hydrogel) loaded with aspirin and bone mesenchymal stem cells (BMSCs) was developed to enhance osteogenesis and immune regulation in small irregular bone defects. OA hydrogels possessed self-healing and shear-thinning properties due to dynamic/covalent hydrazone bonds between aldehyde-modified hyaluronic acid methacrylate (ADH-HAMA) and oxidized hyaluronic acid (OHA). By photopolymerization of the enclosed HAMA, the OADC hydrogel was further reinforced, making it more suitable for cell proliferation. In vitro , composite hydrogels improved the osteogenic differentiation of BMSCs. Additionally, it promoted the M2 polarization of human monocytic leukemia (THP-1) cells. In vivo , the synergistic effect of acetylsalicylic acid (ASA) and BMSCs encapsulated within the OADC hydrogel promoted new bone formation in rat calvaria through increased recruitment and polarization of M2 macrophages. These findings underscore the significant promise of hydrogels for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Although biological scaffolds containing bone morphogenetic protein-2 (BMP-2) have been widely used for osteogenic therapy, achieving stable and controlled release of BMP-2 remains a challenge. Herein, a novel BMP-2 sustained-release system composed of carboxymethyl chitosan (CMCS)/polyethylene glycol (PEG)/heparin sulfate (HS) (CMCS/PEG/HS) was constructed with a Schiff base reaction, yielding an injectable hydrogel for the release of BMP-2 in a controlled manner. For the CMCS/PEG/HS/BMP-2 hydrogel, the HS component had a negatively charged structure, which can bind to positively charged growth factors and prevent early hydrolytic metabolism of growth factors, thus achieving sustainable release of BMP-2. Notably, the release of BMP-2 in hydrogels was dependent mainly on degradation of the hydrogel matrix rather than simple diffusion. Generally, the CMCS/PEG/HS/BMP-2 hydrogel scaffold demonstrated excellent recoverability, good injectability, excellent biocompatibility and high adaptability, as well as efficient self-healing features to occupy irregularly shaped bone marrow cavities. The in vitro results revealed that the CMCS/PEG/HS/BMP-2 hydrogel promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, the in vivo results suggest that the hydrogel has promising osteogenic effects that promote bone regeneration in a skull bone defect model. The injectable hydrogel scaffold shows great promise for bone treatment in the future. [ABSTRACT FROM AUTHOR]

The rising prevalence of global antibiotic resistance evokes the urgent requirement to explore the alternative antimicrobial candidates. It is of great significance to overcome these serious threats of multidrug-resistant bacterial infections and difficult-to-heal cutaneous wounds to human health. Herein, we proposed a rapidly in situ forming innovative antibiotic-free hydrogel dressing with excellent biocompatibility, easy injectability, strong tissue adhesion and superior antibacterial activity against drug-resistant bacteria. An octa-armed poly(ethylene glycol) amine (Octa-PEG-NH 2) was quickly crosslinked with a green industrial microbicide tetrakis (hydroxymethyl) phosphonium chloride (THPC) to form an antibacterial hydrogel (OPTH) by simple mixing without any other initiators or crosslinkers. A significant broad-spectrum antibacterial efficacy was demonstrated against Gram-positive Staphylococcus aureus (S. aureus), Gram-negative Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). Significantly, benefiting from its flexible injectability and reliable tissue adhesion, the excellent antibacterial performances were further evidenced by employing human-induced pluripotent stem cell (iPSC)-derived skin organoids in a 3D culture system and rat animal wound models in vivo with MRSA infection, thus allowing for reepithelization promotion and wound healing. Collectively, the findings not only propose a facile gelatinization strategy for readily accessible antibiotic-free hydrogel dressings for effective MRSA therapy but also hold great clinical translation potential in obliterating multi-pathogenic bacteria and accelerating wound healing. An antibiotic-free hydrogel dressing with easy injectability, excellent biocompatibility and strong tissue adhesion displays superior broad-spectrum antibacterial efficacy and promoting wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice. • An injectable alginate hydrogel containing probiotics and Squid ink was designed. • The hydrogel displayed excellent photothermal antibacterial property. • The hydrogel showed antioxidant, enhanced proliferating, and immune regulating properties. • The hydrogel could treat MRSA infected wounds in multiple stages. [ABSTRACT FROM AUTHOR]

Skin wound dressings are commonly utilized for the treatment of skin injuries, as they effectively facilitate wound healing and possess anti-inflammatory and antibacterial properties. However, conventional dressings fail to inhibit ROS production and promote vascularization, leading to delayed wound healing. Here, we developed injectable self-crosslinking hydrogels through thiolated hyaluronic acid (HASH/rhCOLIII) with enhancing the ROS inhibitory capacity while preserving the cell adhesion ability of hyaluronic acid. Additionally, recombinant humanized collagen type III (rhCOLIII) is incorporated via electrostatic adsorption to further enhance mechanical strength and angiogenesis properties of the hydrogel. The HASH/rhCOLIII demonstrated excellent biocompatibility, remarkable ROS scavenging ability, as well as hemostatic and angiogenic properties. Cell experiment results show that HASH/rhCOLIII has excellent biocompatibility and can significantly promote angiogenesis. Animal experiments results showed that HASH/rhCOLIII exhibits anti-inflammatory effects, significantly accelerating wound healing in a full-thickness skin defect model. These findings highlight that HASH/rhCOLIII hydrogel holds great promise as an advanced dressing for effective wound healing. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) is one of the most effective approaches for the minimally invasive treatment of early gastrointestinal cancers. Submucosal injections help safely and successfully remove lesions during ESD by elevating the mucosa and separating the submucosal muscle layer. Herein, we report dynamic injectable sodium alginate hydrogels (ISAHs) with shear-thinning for ESD surgery, which were easily fabricated by the sulfhydryl group of GSH-modified sodium alginate (SA-GSH) reacting with the aldehyde group of oxidized sodium alginate (OSA) at room temperature. ISAHs have advantageous self-healing abilities and antioxidant activity. Additionally, according to an in vitro test on porcine colorectal submucosal lifting, the submucosal elevation heights created by ISAHs were 13 % -18 % greater than those created by commercial ESD solutions (0.4 w / v % sodium hyaluronate). These properties and biocompatibility were confirmed in vitro and in vivo experiments. ISAHs will hopefully become a novel submucosal injectable hydrogel to assist ESD surgery. • ISAHs are shear-thinning and can be injected by an endoscopic injection needle. • ISAH have desirable self-healing properties and can effectively elevate lesions. • ISAHs with good antioxidant activity have the potential to reduce the inflammation. • ISAHs have more sustained submucosal lift than the commercial ESD solution. [ABSTRACT FROM AUTHOR]

Cutaneous wound management remains a major concern due to uncontrolled inflammation and bacterial infection in clinical care. A desirable hydrogel dressing with antibacterial and antioxidative properties can drive wound healing by inhibiting infection and inflammation. Herein, a multifunctional hydrogel based on polylysine- graft -cysteine (EPL-SH)/oxidized dextran (ODex) was fabricated for promoting skin tissue regeneration. The engineered hydrogel possessed versatile properties including tunable gelation time (60–300 s), typical rheological behavior, suitable swelling and degradation progress, injectable and self-healing ability. The unique hydrogels also displayed promising tissue adhesiveness, high cell affinity, excellent antioxidant and antimicrobial activity. Furthermore, the in vivo full-thickness skin defect experiment demonstrated the simple-to-implement injectable hydrogels could significantly promoting wound healing by improving the collagen deposition and angiogenesis. The manufacture of our multifunctional hydrogels dressing affords a new strategy for improving efficacy of cutaneous wound treatment. [Display omitted] • The oxidized dextran and thiolated ε-poly- l -lysine and were successfully synthesized. • A multi-functional injectable self-healing Dex/EPL hydrogel dressing was designed. • The hydrogel exhibited good antibacterial and free radical scavenging capacity. • The hydrogel has better efficacy on promoting wound repair than commercial dressing. [ABSTRACT FROM AUTHOR]

The development of novel wound dressings with highly effective antibacterial and accelerating wound healing properties has become the focus of current research. In this study, a novel and injectable lactoferrin (LF)/lithium magnesium silicate hydrogel (LMSH) was first synthesized through a simple electrostatic interaction method. The physical and biological properties are systematically characterized. The results show that the synthesized LF/LMSH has good antibacterial properties and biocompatibility. More importantly, it can effectively promote wound healing in the rat full-thickness skin wound model after 14 days post-operation, and the healing rate can reach 99.1 %, which is much higher than that of other groups. Meanwhile, histochemical and immunofluorescent staining confirm that the prepared injectable LF/LMSH has good pro-collagen deposition, pro-angiogenic and anti-inflammatory properties. The healed wounds present a consistently thickened epidermis with more follicular and glandular structures, indicating the great potential of the prepared material for wound management. [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]

Uterine scar was one of the long-term complications cesarean section. In this study, an thermo-responsive injectable hydrogel loaded with human umbilical cord mesenchymal stem cells (UCMSCs) and asiaticoside microspheres (AMs) was used for uterine scar repair, which was prepared by optimizing the mixed ratio of aldehyde-functionalized Pluronic F127 (F127-CHO) and adipic dihydrazide-modified hyaluronic acid (AHA). The asiaticoside was loaded in Poly (DL-lactide- co -gycolide) (PLGA) by emulsion- diffusion-evaporation method. The hydrogel had appropriate pore size, good mechanical property, and slow release ability of asiaticoside. In vitro cell experiments demonstrated that F127-CHO/AHA/AMs could effectively promote stem cell adhesion and proliferation, promote angiogenesis, and provide a suitable microenvironment for cell survival. The F127-CHO/AHA/AMs/UCMSCs hydrogel was further used to repair uterine scar in female SD rats. The results showed that the prepared hydrogel could promote the proliferation of rat endometrial cells, promote the regeneration of glands, reduce the degree of endometrial fibrosis and restore the morphology of uterine cavity. The hydrogel could upregulate expression of Ki67 and IGF-1, downregulate TGF-β1 expression and promote M1-M2 transition of macrophages. This study confirmed that the prepared hydrogel could be used as an effective transplantation strategy, which could be expected to achieve clinical transformation of uterine scar repair. [ABSTRACT FROM AUTHOR]

Pulpitis is inflammation of the dental pulp, often caused by bacterial infection from untreated cavities, leading to pain. The main challenge in treatment is eliminating infection while preserving tooth vitality. This study aims to address this challenge by developing a hydrogel for convenient insertion into the root canal system, securely attaching to dentin walls. An injectable hydrogel system is developed by chemically cross-linking natural polysaccharide pectin with gelatin (GPG) through reversible Schiff base reaction. The GPG system was then used to encapsulate and release drugs, such as ciprofloxacin (CIP) for infection prevention and deferoxamine (DFO) for promoting blood vessel proliferation and reducing inflammatory reactions. The GPGs absorbed significant amounts of CIP and DFO, enabling sustained release over a nearly ten-day period. When subcutaneously implanted, the GPGs formed stable gel depots, with only 50 % of the gels degrading after 3 weeks, indicating a sustained biodegradation pattern. Additionally, the GPG system demonstrated excellent antibacterial activity against both gram-negative and gram-positive bacteria. Results from in vitro scratch healing tests and in ovo chorioallantoic membrane chick model tests showed promising biocompatibility and promotion of vascular proliferation by the GPG. This study heralds a novel frontier in endodontic therapeutics, poised to potentially enable dental pulp regeneration., 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.)

Wound infections caused by microorganisms often give rise to extensive inflammation and vascular damage that compromise the wound healing process. Designing approaches to more effectively controlling wound infections and accelerating this healing process are urgently needed. This study was designed with the goal of synthesizing an injectable, double cross-linked hydrogel suitable for use when treating infected wounds. After initially synthesizing methacrylated polylysine (PLMA) through polylysine grafting with methacrylic anhydride, CGRP and PLMA were incorporated into a PEG hydrogel network through reactions between NHS-activated carboxyl esters and amino groups (NH₂). PLMA was also employed to enhance the self-crosslinking activity, culminating in the production of PEG/PLMA/CGRP double cross-linked hydrogels. After injection these hydrogels were capable of undergoing rapid molding such that they were able to conform to the irregularly shaped wound contours. This PEG/PLMA/CGRP formulation was capable of mimicking nerve ending-mediated CGRP secretion to control wound healing, while also exhibiting robust antioxidant, anti-inflammatory, and pro-angiogenic properties. In addition, PEG/PLMA/CGRP hydrogels in vitro showed robust resistance to S. aureus and E. coli. In a rat model of S. aureus-mediated wound infection, this hydrogel markedly promoted wound healing. PEG/PLMA/CGRP hydrogels are thus an effective tool for use in the context of infected wound healing., 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. Published by Elsevier B.V.)

Up to now, the clinical treatment of spinal cord injury (SCI) to recover the locomotion function, sensory function, and autonomic function of patients is a global medical challenge. In this study, based on the excellent effects of Tetramethylpyrazine (TMP) on regulating pathological micro-environment, we designed a new injectable conductive hydrogel consists of water-soluble polypyrrole (Ppy), agar, and TMP. The TMP@PA hydrogel has excellent physicochemical properties, bio-safety, and drug release ability, which can be injected into lesions in situ without secondary injury for SCI. Our in vivo and in vitro experiments have demonstrated that the TMP@PA hydrogel can not only fill the spinal cord cavity to reconstruct the electrical conduction pathway but also release TMP continuously to inhibit ferroptosis by regulating nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy regulated by Yes-Associated Protein (YAP) to promote SCI repair. Collectively, TMP@PA hydrogel may be an effective tissue engineering scaffold to treat SCI with highly promising clinical applications., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Thermosensitive nanoparticles with phase transition abilities have been considered as suitable materials in biomedical fields, especially drug delivery systems. Moreover, electroactive injectable hydrogels supporting bone regeneration of the elderly will highly be desired in bone tissue engineering applications. Herein, thermosensitive nanoparticles were fabricated using chitosan/poly(N-isopropyl acrylamide) for simvastatin acid delivery. The nanoparticles were incorporated into electroactive injectable hydrogels based on aniline pentamer/silk fibroin/polyacrylamide containing vitamin C. The nanoparticles had thermosensitive properties as simvastatin acid had higher release rates at 37 than 23 °C without significant burst release. The hydrogels also revealed an appropriate gelation time, stable mechanical and rheological characteristics, high water absorbency, and proper biodegradability. In vitro studies indicated that the hydrogel was biocompatible and nontoxic, especially those containing drugs. Implantation of the hydrogels containing both simvastatin acid and vitamin C into the critical calvarial bone defect of the aged rat also demonstrated significant enhancement of bone healing after 4 and 8 weeks post-implantation. We found that the electroactive injectable hydrogels containing thermosensitive nanoparticles exhibited great potential for treating bone defects in the elderly rats [ABSTRACT FROM AUTHOR]

Management of infections at ocular injury often requires prolonged and high dose of antibiotic, which is associated with challenges of antibiotic resistance and bacterial biofilm formation. Tissue glues are commonly used for repairing ocular tissue defects and tissue regeneration, but they are ineffective in curing infection. There is a critical need for antibacterial ocular bio-adhesives capable of both curing infection and aiding wound closure. Herein, we present the development of an imine crosslinked N -(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC)‑silver chloride nanocomposites (QAm 1 -Ag x) and poly-dextran aldehyde (PDA) based bactericidal sealant (BacSeal). BacSeal exhibited potent bactericidal activity against a broad spectrum of bacteria including their planktonic and stationary phase within a short duration of 4 h. BacSeal effectively reduced biofilm-embedded MRSA and Pseudomonas aeruginosa by ∼99.99 %. In ex-vivo human cornea infection model, BacSeal displayed ∼99 % reduction of ocular infection. Furthermore, the hydrogel exhibited excellent sealing properties by maintaining ocular pressure up to 75 mm-Hg when applied to human corneal trauma. Cytotoxicity assessment and hydrogel-treated human cornea with a retained tissue structure, indicate its non-toxic nature. Collectively, BacSeal represents a promising candidate for the development of an ocular sealant that can effectively mitigate infections and may assist in tissue regeneration by sealing ocular wounds. [Display omitted] [ABSTRACT FROM AUTHOR]

The wound healing process of the diabetic wound is often hindered by excessive oxygen free radicals and infection. An ideal wound dressing should possess great reactive oxygen species (ROS) scavenging property and considerable antibacterial ability. In this study, we facilely constructed a novel hydrogel dressing with excellent ROS scavenging property and outstanding antibacterial performance by introducing tannic acid (TA) into quaternized chitosan (QCS) matrix. Attributing to the suitable physical crosslinking between TA and QCS, this QCS/TA hydrogel was endowed with injectable and self-healing properties, which could avoid the various external squeezing on the irregular shape by wound dressing. The results showed that it could promote coagulation, suppress inflammation and expedite collagen deposition in the skin defect model of diabetic rats. This study provides a facile and convenient method for constructing injectable hydrogel dressing, which has application potentials in the clinical management of diabetic wounds. • An injectable hydrogel (QT) composed of quaternized chitosan and tannic acid was designed. • One-step fabrication of QT hydrogel was achieved via alkali neutralization strategy. • QT hydrogel possessed robust antibacterial and ROS scavenging capabilities. • QT hydrogel significantly accelerated skin tissue regeneration in diabetic wounds. [ABSTRACT FROM AUTHOR]

Injectable hydrogels have been known as promising materials for the regeneration of irregular shape tissue defects. In this study, novel thermosensitive methylcellulose (MC) hydrogels containing bassorin (Ba) and halloysite nanotubes (HNTs) have been developed for application in bone tissue engineering. Bassorin isolated from gum tragacanth (GT) with the concentration of 0.25-1.5 w / v % was blended with MC. The best MC/Ba gel (containing 0.5% bassorin) was chosen based on the results of injectability and rheological tests. HNTs (1-7%) were added to this formulation and tested for the physicochemical, mechanical, rheological, degradation, swelling, and biological properties. In vitro biological evaluations including cell proliferation (by MTT assay), cell attachment (by SEM), osteogenic activity (by Alizarin Red staining and alkaline phosphatase assay), and osteogenic gene expression (by quantitative real-time polymerase chain reaction) were done using MG-63 cells. Results showed that bassorin led to the increased gel-forming ability (at a lower temperature) and mechanical properties of MC hydrogel. The presence of HNTs and bassorin affected the degradation rate and swelling degree of MC-based hydrogel. Results showed significant enhancement in cell proliferation, differentiation, and mineralization, as well as higher bone-specific gene expression of the cell on bassorin and HNTs incorporated MC compared to pure MC hydrogel. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [Display omitted] • An injectable and dual-enzymatically cross-linked gelatin hydrogel was used to load BMSC for TBI treatment • Low cross-linked gelatin hydrogel obviously enhances cellular viability, neural differentiation, and neurotrophin secretion • This GH/MSC hydrogel implantation could promote the neurogenesis and functional reconstruction of TBI mice [ABSTRACT FROM AUTHOR]

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. • Dual-crosslinked PECMA/GelMA networks as hemostatic hydrogels • Hydrogels exhibit tunable swelling, porosity and mechanical properties. • Hybrid hydrogels significantly decreased the in vitro coagulation time. • Hydrogel injection and in situ photocrosslinking onto the wound bed • Easily removed from the wound, preventing secondary injury. [ABSTRACT FROM AUTHOR]

Wound infections, posing a grave risk of severe physical consequences and even mortality, exact a substantial financial toll on society, rendering them among the most formidable challenges confronting our world today. A critical imperative is the development of hydrogel dressings endowed with immune-regulating and antibacterial properties. This study is founded upon the symbiotic physical and efficacious attributes of two small natural molecules. An injectable hydrogel is meticulously crafted by encapsulating puerarin (PUE) into tyramine-modified hyaluronic acid, subsequently introducing rhein (RHE), and catalyzing the formation of inter-phenol crosslinks with H 2 O 2 /horseradish peroxidase (HA-Tyr-R@P). Exhibiting a favorable microenvironmental impact the developed hydrogel attains an antibacterial efficacy exceeding 95 %, coupled with a wound closure rate twice that of the control group. HA-Tyr-R@P hydrogels not only inhibit bacterial growth but also mitigate inflammation, fostering wound healing, owing to their harmonized physicochemical characteristics and synergistic therapeutic effects. This work underscores the creation of a singular, versatile hydrogel platform, negating the complexities and side effects associated with pharmaceutical preparations. Furthermore, it offers new ideas for the formulation of RHE-based hydrogels for wound healing, emphasizing the pivotal role of natural small molecules in advancing biological materials. [ABSTRACT FROM AUTHOR]

The recent use of PARP inhibitors (PARPi) in the maintenance treatment of ovarian tumor has significantly improved the survival rates of cancer patients. However, the current oral administration of PARP inhibitors fails to realize optimal therapeutic effects due to the low bioavailability in cancerous tissues, and often leads to a range of systemic adverse effects including hematologic toxicities, digestive system reactions, and neurotoxicities. Therefore, the demand for an advanced drug delivery system that can ensure effective drug administration while minimizing these unfavorable reactions is pressing. Injectable hydrogel emerges as a promising solution for local administration with the capability of sustainable drug release. In this study, we developed an injectable hydrogel made from aminated hyaluronic acid and aldehyde-functionalized pluronic127 via Schiff base reaction. This hydrogel exhibits excellent injectability with short gelation time and remarkable self-healing ability, and is applied to load niraparib. The drug-loaded hydrogel (HP@Nir hydrogel) releases drugs sustainably as tested in vitro as well as displays significant anti-proliferation and anti-migratory properties on human epithelial ovarian cancer cell line. Notably, HP@Nir hydrogel effectively suppresses the growth of ovarian cancer, without significant adverse reactions as demonstrated in animal studies. Additionally, the developed hydrogel is gradually degraded in vivo for around 20 d, while maintaining good biocompatibility. Overall, the injectable hydrogel loaded with niraparib provides a secure and efficient strategy for the treatment and management of ovarian cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Bacterial infected wounds, which is characterized by easy infection, multiple inflammation and slow healing, is a complex symptom, resulting from metabolic disorder of the wound microenvironment. In this study, a series of self-healing double-network hydrogels based on KGRT peptide (Lys-Gly-Arg-Thr) with antibacterial, anti-inflammatory and optimizing cellular functions were designed to promote the healing of infected wounds with full-thickness skin defects. Moreover, the dextran hydrogelintroduces a large number of side chains, which are entangled with each other in the Schiff base network to form an interpenetrating structure. The hydrogel might regulate cell metabolism, differentiation and vascular endothelial growth factor (VEGF) function. Importantly, both in vitro and in vivo data showed that hydrogel not only has good antibacterial properties (99.8 %), but also can eradicate bacterial biofilm, effectively reduce inflammation (down-regulated IL-1β, TNF-α and ROS) and accelerate chronic wound healing process by speeding-up wound closure, increasing granulation tissue thickness, collagen deposition, angiogenesis (up-regulated CD31). The hydrogel could up-regulate mRNA expression of PI3K, AKT, ERK, eNOS, HIF-1α and VEGF, which were correlated with wound healing. Consistently, the hydrogel could promote infected wounds healing and inhibit inflammation through ERK/eNOS signaling pathway. Collectively, hydrogel has excellent clinical application potential for promoting infected wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

Drug delivery to posterior segment of eye has always been challenging. The aim of the present study was to provide a novel injectable, shear sensitive hydrogel based on tragacanthic acid (TA) with three kinds of acetate salts as cross-linker. Rheological properties by strain and shear stress sweep measurements and also dynamic rheological experiments including frequency and time sweep measurements were studied. Biological studies comprising, cell culture, Draize test on rabbit eyes and histopathological tests were done. The results showed the optimized hydrogel was biocompatible, injectable and owning acceptable firmness in rest state after injection. Healing time of the hydrogel was 46 s and was shear-sensitive. It showed no cytotoxicity on HUVEC cells. No allergic reaction was seen in Draize test and histological examination showed integrity of the retinal layers with no evidence of pathological changes, such as deformations, degeneration, or inflammation. TA hydrogel is promising in ocular drug delivery. Unlabelled Image • Tragacanthic acid (TA) was obtained from fractionation of Tragacanth gum. • Shear sensitive hydrogel obtained from addition of sodium acetate (NaOAc) to TA solution • Loss factor value of TA-NaOAc hydrogel showed that it had a strong viscoelastic gel like property. • Dynamic storage modulus G ′ and loss modulus G″ increased with frequency and its healing time was 46 s. • TA-NaOAc hydrogel caused no cytotoxicity, allergic reaction or histological changes in eye. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) is widely used as a filler owing to its excellent biocompatibility and biodegradability. However, commercial HA-based filler products have some limitations and can cause side effects due to the presence of residual chemical crosslinking agents. In this study, tyramine (Tyr) was introduced into HA to impart photocrosslinking ability to HA, and a photocrosslinked hydrogel was formed using a less toxic vitamin B2 derivative as a photoinitiator. For injection, an injectable filler was prepared by converting the photocrosslinked hydrogel to a microgel form. The crosslinking of the tyramine-modified HA (HA-Tyr) hydrogel, which can be applied as a soft tissue filler, increased with an increase in the irradiation time, and the crosslinked hydrogel showed excellent mechanical strength, elastic recovery rate, and injectability. It also showed non-cytotoxicity and cell proliferation behavior in fibroblasts. Therefore, injectable HA hydrogels have great potential as an alternative to conventional commercial dermal fillers. [ABSTRACT FROM AUTHOR]

Regulating the activity of matrix metalloproteinases (MMPs) is a potential strategy for osteoarthritis (OA) therapy, although delivering this effect in a spatially and temporally localised fashion remains a challenge. Here, we report an injectable and self-healing hydrogel enabling factor-free MMP regulation and biomechanical competence in situ. The hydrogel is realised within 1 min upon room temperature coordination between hyaluronic acid (HA) and a cell-friendly iron-glutathione complex in aqueous environment. The resultant gel displayed up to 300% in shear strain and tolerance towards ATDC 5 chondrocytes, in line with the elasticity and biocompatibility requirements for connective tissue application. Significantly enhanced inhibition of MMP-13 activity was achieved after 12 h in vitro, compared with a commercial HA injection (OSTENIL® PLUS). Noteworthy, 24-hour incubation of a clinical synovial fluid sample collected from a late-stage OA patient with the reported hydrogel was still shown to downregulate synovial fluid MMP activity (100.0 ± 17.6% ➔ 81.0 ± 7.5%), with at least comparable extent to the case of the OSTENIL® PLUS-treated SF group (100.0 ± 17.6% ➔ 92.3 ± 27.3%). These results therefore open up new possibilities in the use of HA as both mechanically-competent hydrogel as well as a mediator of MMP regulation for OA therapy. Fe-coordination to HA in aqueous environment generates an injectable, self-healing and biomechanically viable gel and enables factor-free regulation of matrix metalloproteinases. Unlabelled Image • A non-covalent hyaluronic acid (HA) gel was realised via chelation of Fe3+ to HA. • Addition of an Fe3+-GSH complex to an aqueous solution of HA led to full gelation. • Fe-coordination provided the self-healing HA gel with chondrocyte tolerance. • The gel demonstrated higher MMP-13 regulation than a commercial HA joint injection. • The gel successfully inhibited synovial fluid MMPs of an osteoarthritic patient. [ABSTRACT FROM AUTHOR]

Injectable hydrogels with pH-sensitive and self-healing properties have great application potential in the field of anti-cancer drug carriers. In this work, an injectable hydrogel is prepared using 4armPEG-benzaldehyde (4armPEGDA) and N-carboxyethyl chitosan (CEC) as a new drug carrier. The gelation time, equilibrium swelling rate, degradation time, and dynamic modulus of the injectable hydrogels can be adjusted by merely changing the concentration of 4armPEGDA. The volume of the hydrogel shrinks at pH 5.6 and expands at pH 7.4, which helps to control the release of anti-cancer drug. At pH 5.6, the hydrogels show a fast and substantial Dox release effect, which is five times higher than that at pH 7.4. In vitro cumulative drug release of all the hydrogels reached equilibrium on about the fourth day, and the hydrogel is completely degraded within five days, which contributes to the Dox-loaded hydrogel to further release the remaining Dox. Moreover, the Dox-loaded hydrogel shows a strong inhibitory effect on the growth of human hepatocellular carcinoma cells (HepG2). Finally, the anti-tumor model experiment in vivo demonstrated that the Dox-loaded hydrogel can significantly inhibit tumor growth within five days. Therefore, such injectable hydrogels are excellent carriers for the potential treatment of hepatocellular carcinoma. Unlabelled Image • Both 4armPEGDA and CEC, with excellent water-solubility, are synthesized by a facile one-step chemical modification. • The gelation time, equilibrium swelling rate, dynamic modulus and degradation of the hydrogels can be easy adjusted. • The hydrogels have excellent self-healing and pH-sensitive properties. • The treatment of Dox-loaded hydrogel in local tumor is significantly superior to other drug-delivery methods. [ABSTRACT FROM AUTHOR]

Hydrogel scaffolds have been frequently utilized due to their ability to absorb water and develop similar body cell conditions. Specific drug delivery to the tissues ensures less adverse side effects and more efficiency. In the present study, carboxymethyl chitosan (CMC)-methylcellulose (MC)-pluronic (P) and zinc chloride hydrogels containing meloxicam loaded into nanoparticles were developed and characterized. Nanoparticles were incorporated at 3.5, 4.5 and 5.5% (w/v). Hydrogels containing the same amounts of the meloxicam solution were also prepared. Gelation time, swelling and degradation of the hydrogels were investigated. Hydrogels were characterized by scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, and rheological analysis. Meloxicam release, chondrocytes attachment and growth on the hydrogels were also studied. Gelation time, swelling and the degradation rate of the hydrogels were found to be decreased by nanoparticles and increased with the addition of the meloxicam solution. SEM images also showed three-dimensional networks. The ATR-FTIR bands were shifted to the lower wave numbers in the hydrogels containing nanoparticles and shifted to the upper ones in the hydrogels containing meloxicam solution. Storage (G′) and loss (G″) modulus were increased by the nanoparticles and reduced by the meloxicam solution. 100% of meloxicam was released from the hydrogels containing the meloxicam solution within 20 days, but it was released slowly from the hydrogels containing nanoparticles in 37days. Chondrocytes metabolic activity was increased on the 6th and 10th days for all hydrogels. Hydrogel containing nanoparticles showed good biocompatibility, bioadhesion, cell growth and expansion. The hydrogel could be, therefore, suitable as a new composite biomaterial for the regeneration of articular cartilage and meloxicam delivery to control the pain and inflammation in osteoarthritis. [ABSTRACT FROM AUTHOR]

Injectable hydrogels are gaining prominence as a biocompatible, minimally invasive, and adaptable platform for cartilage tissue engineering. Commencing with their synthesis, this review accentuates the tailored matrix formulations and cross-linking techniques essential for fostering three-dimensional cell culture and melding with complex tissue structures. Subsequently, it spotlights the hydrogels' enhanced properties, highlighting their augmented functionalities and broadened scope in cartilage tissue repair applications. Furthermore, future perspectives are advocated, urging continuous innovation and exploration to surmount existing challenges and harness the full clinical potential of hydrogels in regenerative medicine. Such advancements are crucial for validating the long-term efficacy and safety of hydrogels, positioning them as a promising direction in regenerative medicine to address cartilage-related ailments. [ABSTRACT FROM AUTHOR]

Ferroptosis has drawn great attention to tumor treatments over the past decade. However, how to specifically boost tumoral redox imbalance by simultaneously superimposing iron-mediated reactive oxygen species and undermining antioxidative pathways at the tumor site is still a significant challenge in ferroptosis-based tumor ferrotherapy. In this study, we designed an in situ generable hydrogel that contains paclitaxel/chlorin e6-loaded iron-based metal-organic framework (Fe-MOF) nanoparticles for enhanced breast tumor ferrotherapy by multiplex magnifying redox imbalance. The polysaccharide sodium alginate can crosslink with tumoral calcium ions to generate a hydrogel patch, which promotes the retention of Fe-MOF and therapeutic molecules. The Fe-MOF holds peroxidase/glutathione oxidase mimicking properties, resulting in OH generation via the Fenton reaction and glutathione consumption. Local ultrasound treatment facilitates the release of therapeutics and stimulates the generation of signet oxygen by activating the sonosensitizer chlorin e6. In the meanwhile, the low-dose paclitaxel reduces tumoral pH value by downregulating the glutaminolysis-related gene (SLC7A11) which in turn enhances the catalytic activity of Fe-MOF and inhibits antioxidative pathways, respectively. Both in vivo and in vitro experiments show that our designed hybrid hydrogels can induce significant ferrotherapeutic effects by augmenting the tumoral oxidative stresses. Designing in situ generable hybrid polysaccharide hydrogels (Fe-MOF/PTX/Ce6@ALG) that can generate numerous ROS and deplete GSH to amplify the tumoral redox imbalance, resulting in a high tumor ferrotherapeutic efficacy. [Display omitted] • We designed an in situ -formed hybrid polysaccharide hydrogel for responsive drug delivery and synergistic tumor ferrotherapy. • The in situ generable hybrid hydrogels can promote the retention of drugs and nanoparticles in tumor sites. • PTX could reduce cellular pH to enhance Fenton activity of Fe-MOF nanoparticles. • The hydrogel could impair antioxidant system by GSH consumption and SLC7A11 inhibition. [ABSTRACT FROM AUTHOR]

The simultaneous regeneration of articular cartilage and subchondral bone is a major challenge. Bioinspired scaffolds with distinct regions resembling stratified anatomical architecture provide a potential strategy for osteochondral defect repair. Here, we report the development of an injectable and bilayered hydrogel scaffold with a strong interface binding force. In this bilayer hydrogel, composed of carbonyl hydrazide grafted collagen (COL-CDH) and oxidized chondroitin sulfate (OCS), which are derivatives of osteochondral tissue components, in combination with poly (ethylene glycol) diacrylate (PEGDA), functions as a cartilage layer; while zinc-doped hydroxyapatite acts as a subchondral bone layer that is based on the cartilage layer. The strong interface between the two layers involves dynamic amide bonds formed between COL-CDH and OCS, and permanent C C bonds formed by PEGDA radical reactions. This bilayer hydrogel can be used to inoculate adipose mesenchymal stem cells which can then differentiate into chondrocytes and osteoblasts, secreting glycosaminoglycan, and promoting calcium deposition. This accelerates the regeneration of cartilage and subchondral bone. Micro-CT and tissue staining revealed an increase in the amount of bone present in new subchondral bone, and new tissues with a structure similar to normal cartilage. This study therefore demonstrates that injectable bilayer hydrogels are a promising scaffold for repairing osteochondral defects. [ABSTRACT FROM AUTHOR]

Oligosaccharide-containing macromolecular bio adhesives are emerging as highly promising eco-friendly materials to enhance the cytocompatibility of viscous hydrogels for wound healing applications. In our prior research, we extensively elucidated the properties of branch -structure fructo-oligosaccharides derived from Polygonatum Cyrtonema Hua (referred to as PCOS). However, the characteristics of hydrogels based on fructo-oligosaccharides remain to be fully explored. In present work, we developed an injectable, PCOS/carboxymethyl cellulose (CMC) hydrogel which is a dual ion-physical cross-linked hydrogel that can be considered as a potential diabetic wound dressing. The tests showed that the optimal ratios for hydrogel preparation were 2 % CBM 940 (Carbomer 940), 5 % CMC and 10 % PCOS. The resultant hydrogel was formulated into composite hydrogels that were then used for the treatment of full-thickness excisional wounds in a db/db diabetic mouse model. Wound closure and histological evaluation confirmed its beneficial effect on wound healing. Further morphological analysis through scanning electron microscopy images revealed a porous hydrogel structure, while Fourier-transform infrared spectroscopy provided structural insights on the crosslinking reaction. Physicochemical properties of the hybrid hydrogels determined by rheological properties, thermogravimetric, water loss rate, et al., indicated that the double crosslinking PCOS/CMC hybrid hydrogel showed enhanced dynamic mechanical properties and water retention capacity compared to the CMC cellulose matrix hydrogels. Thus, this novel PCOS-hybrid hydrogel exhibited good dissolvability and injectable properties, which was proved to facilitate for the diabetic wound healing both in vitro and in vivo test and holds a potential clinical application in the wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

Hemorrhage stands out as a leading factor contributing to fatalities in trauma cases. Hemorrhage is associated with the process of hemostasis. Hemostasis is the primary stage of wound healing. Hydrogels can aid in hemostasis and minimize the duration of wound healing. Calcium is one of the clotting factors and is a key component for the activation of the coagulation cascade. In this work, we have developed a polymeric hydrogel matrix made up of κ-carrageenan and sodium alginate containing a calcium silica nanocomposite and a natural drug, namely the bark of L. coromandelica. The nanocomposite was characterized using various modalities such as XRD, FTIR, FESEM and HRTEM. The rheological and morphological properties of the pure and composite hydrogels were examined. The antimicrobial activity, hemocompatibility and hemostatic efficacy of the materials were studied using various in vitro assays including bacterial growth curve analysis, colony counting, anti-biofilm assay, hemolysis assay and in vivo clotting studies. The drug incorporated nanocomposite hydrogel exhibited superior activity in animal models. [ABSTRACT FROM AUTHOR]

Novel injectable thermosensitive PNIPAM/hyaluronic acid hydrogels containing various amounts of chitosan-g-acrylic acid coated PLGA (ACH-PLGA) micro/nanoparticles were synthesized and designed to facilitate the regeneration of cartilage tissue. The ACH-PLGA particles were used in the hydrogels to play a triple role: first, the allyl groups on the chitosan-g-acrylic acid shell act as crosslinkers for PNIPAM and improved the mechanical properties of the hydrogel to mimic the natural cartilage tissue. Second, PLGA core acts as a carrier for the controlled release of chondrogenic small molecule melatonin. Third, they could reduce the syneresis of the thermosensitive hydrogel during gelation. The optimum hydrogel with the minimum syneresis and the maximum compression modulus was chosen for further evaluations. This hydrogel showed a great integration with the natural cartilage during the adhesion test, and also, presented an interconnected porous structure in scanning electron microscopy images. Eventually, to evaluate the cytotoxicity, mesenchymal stem cells were encapsulated inside the hydrogel. MTT and Live/Dead assay showed that the hydrogel improved the cells growth and proliferation as compared to the tissue culture polystyrene. Histological study of glycosaminoglycan (GAG) showed that melatonin treatment has the ability to increase the GAG synthesis. Overall, due to the improved mechanical properties, low syneresis, the ability of sustained drug release and also high bioactivity, this injectable hydrogel is a promising material system for cartilage tissue engineering. Unlabelled Image • Novel injectable hydrogel containing multifunctional microparticles synthesized • PLGA-ACH microparticles act as a both crosslinker and carrier of melatonin. • The porous structure hydrogels show great integration with the natural cartilage. • PLGA-ACH microparticles reduce the syneresis of PNIPAM/HA hydrogels. • Injectable hydrogel is a promising material system for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Herein, we present the synthesis of surface-oxidized cellulose nanofiber (CNF) hydrogel and characterization with various physicochemical analyses and spectroscopic tools as well as its suitability for cellular encapsulation and delivery. The structure-property relationship as shear thinning, thixotropy, creep-recovery and stimuli responsiveness are explored. The CNF hydrogel is capable to inject possessing shear thinning behavior at shear rate (~10 s−1) range in the normal injecting process. In time-dependent thixotropy, the hydrogel showed rapid transform from flowable fluid back to structured hydrogel fully recovering in less than 60 s. The presence of cell-culture media did not alter shear thinning behavior of CNF hydrogel and showed increased thixotropicity with respect to the control gel. The CNF hydrogel forms 3D structures, without any crosslinker, with a wide range of tunable moduli (~36–1000 Pa) based on concentration and external stimuli. The biological characteristics of the thixotropic gels are studied for human breast cancer cells and mouse embryonic stem cells and indicated high cell viability, long-term survival, and spherical morphology. [ABSTRACT FROM AUTHOR]

Abstract Scaffolds for tissue engineering of specific sites such as cardiac, nerve, and bone tissues need a comprehensive design of three dimensional materials that covers all aspects of chemical composition and physical structures, required for regeneration of desired cells. Hydrogels, possessing highly hydrated and interconnected structures, are promising materials for tissue engineering applications. Improvement of an injectable hydrogel from biocompatible polysaccharides and poly‑ N ‑isopropyl acryl amide enriched with Au nanoparticles are the main goal of this study. Two main enhancements in this study are included mixture design of the components and addition of Au nanoparticles to access a homogeneous mixture that have potential application in tissue engineering. Chemical and physical properties of the injectable hydrogel are fully characterized. Addition of Au nanoparticles as a conductive component to enhance cell growth and attachment is investigated through MG-63 cell viability assay. Highlights • An injectable hydrogel was synthesized by chitosan, κ-carrageenan, and poly(NIPAM). • Gold nano-particles were used to enhance MG-63 cell growth and adhesion. • Chemical and physical properties of the hydrogel were examined. [ABSTRACT FROM AUTHOR]

Bone tissue possesses intrinsic regenerative capabilities to address deformities; however, its ability to repair defects caused by severe fractures, tumor resections, osteoporosis, joint arthroplasties, and surgical reconsiderations can be hindered. To address this limitation, bone tissue engineering has emerged as a promising approach for bone repair and regeneration, particularly for large-scale bone defects. In this study, an injectable hydrogel based on kappa-carrageenan- co -N-isopropyl acrylamide (κC-co-NIPAAM) was synthesized using free radical polymerization and the antisolvent evaporation technique. The κC-co-NIPAAM hydrogel's cross-linked structure was confirmed using Fourier transform infrared spectra (FTIR) and nuclear magnetic resonance (1H NMR). The hydrogel's thermal stability and morphological behavior were assessed using thermogravimetric analysis (TGA) and scanning electron microscopy (SEM), respectively. Swelling and in vitro drug release studies were conducted at varying pH and temperatures, with minimal swelling and release observed at low pH (1.2) and 25 °C, while maximum swelling and release occurred at pH 7.4 and 37oC. Cytocompatibility analysis revealed that the κC-co-NIPAAM hydrogels were biocompatible, and hematoxylin and eosin (H&E) staining demonstrated their potential for tissue regeneration and enhanced bone repair compared to other experimental groups. Notably, digital x-ray examination using an in vivo bone defect model showed that the κC-co-NIPAAM hydrogel significantly improved bone regeneration, making it a promising candidate for bone defects. Graphical illustration of the κC-co-NIPAAM injectable hydrogels for bone tissue repair and regeneration after targeted injection at the defected site showing the formation of the dense collagen network and cell migration in the bone repair. [Display omitted] [ABSTRACT FROM AUTHOR]

Injectable hydrogel-based drug delivery systems have attracted more and more attention due to their sustained-release performance, biocompatibility, and 3D network. The present study showed whole pectin-based hydrogel as an injectable drug delivery system, which was developed from oxidized pectin (OP) and diacylhydrazine adipate-functionalized pectin (Pec-ADH) via acylhydrazone linkage. The as-prepared hydrogels were characterized by 1H NMR, FT-IR, and SEM techniques. The equilibrium swelling ratio of obtained hydrogel (i.e., sample gel 5) was up to 4306.65 % in the distilled water, which was higher than that in PBS with different pH values. Increasing the pH of the swelling media, the swelling ratio of all hydrogels decreased significantly. The results that involved the swelling properties indicated the salt- and pH-responsiveness of the as-prepared hydrogels. The drug release study presented that 5-FU can be persistently released for more than 12 h without sudden release. Moreover, the whole pectin-based hydrogel presented high cytocompatibility toward L929 cell lines, and the drug delivery system showed a high inhibitory effect on MCF-7 cell lines. All these results manifested that the acylhydrazone-derived whole pectin-based hydrogel was an excellent candidate for injectable drug delivery systems. [ABSTRACT FROM AUTHOR]

Currently, bio-natural injectable hydrogels are receiving a lot of attention due to their ability to control, adjust, and adapt to random bone defects, in addition, to their ability to mimic the composition of natural bones. From such a viewpoint, this study goal is to prepare and characterize the injectable hydrogels paste based on the natural alginate (Alg) derived from brown sea algae as a polysaccharide polymer, which coupled with nano biogenic-hydroxyapatite (n-HA) prepared from eggshells and enriched with valuable trace elements. The viscosity and mechanical properties of the paste were investigated. As well as the in-vitro study in terms of water absorption and biodegradability in the PBS, biocompatibility and the capability of the injectable Alginate/n-Hydroxyapatite (Alg/n-HA) to regenerate bone for the most suitable injectable form. The injectable hydrogel (BP -B sample) was chosen for the study as it had an appropriate setting time for injecting (13 mins), and suitable compressive strength reached 6.3 MPa. The in vivo study was also carried out including a post-surgery follow-up test of the newly formed bone (NB) in the defect area after 10 and 20 weeks using different techniques such as (SEM/EDX) and histological analysis, the density of the newly formed bone by Dual x-ray absorptiometry (DEXA), blood biochemistry and the radiology test. The results proved that the injectable hydrogels Alginate/n-Hydroxyapatite (Alg/n-HA) had an appreciated biodegradability and bioactivity, which allow the progress of angiogenesis, endochondral ossification, and osteogenesis throughout the defect area, which positively impacts the healing time and ensures the full restoration for the well-mature bone tissue that similar to the natural bone., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Injectable hydrogels are attractive and alternative scaffolds for cell delivery because they could form in situ, simulate natural tissue and fill any shape of defect. This study aimed at fabricating injectable, self-crosslinkable and biomimetic hydrogels based on collagen type II (Col II) and activated chondroitin sulfate (CS-sNHS) under physiological conditions without the addition of any catalysts or crosslinking agents. The inner morphology of hydrogels was detected by scanning electron microscopy, and it showed that fibrous structure formed in the hydrogels. The gelation time, water absorption capacity and the mechanical property of hydrogels were closely related to the weight ratio of Col II and CS-sNHS in hydrogels. Chondrocytes were encapsulated into these hydrogels, and the effect of hydrogels on survival, proliferation, morphology of cells and remolding of extracellular matrix was investigated. The results demonstrated that chondrocytes survived well and showed round or oval morphology in these hydrogels, in addition, the matrix in hydrogels had been remolded and the collagen fibers displayed periodic alternation of light and shade. These results implied that the injectable and self-crosslinkable hydrogels were alternative carriers for chondrocyte delivery. [ABSTRACT FROM AUTHOR]

To date, numerous delivery systems based on either organic or inorganic material have been developed to achieve efficient and sustained delivery of therapeutics. Hydrogels, which are three dimensional networks of crosslinked hydrophilic polymers, have a significant role in solving the clinical and pharmacological limitations of present systems because of their biocompatibility, ease of preparation and unique physical properties such as a tunable porous nature and affinity for biological fluids. Development of an in situ forming injectable hydrogel system has allowed excellent spatial and temporal control, unlike systemically administered therapeutics. Injectable hydrogel systems can offset difficulties with conventional hydrogel-based drug delivery systems in the clinic by forming a drug/gene delivery or cell-growing depot in the body with a single injection, thereby enabling patient compliance and comfort. Carbohydrate polymers are widely used for the synthesis of injectable in situ -forming hydrogels because of ready availability, presence of modifiable functional groups, biocompatibility and other physiochemical properties. In this review, we discuss different aspects of injectable hydrogels, such as bulk hydrogels/macrogels, microgels, and nanogels derived from natural polymers, and their importance in the delivery of therapeutics such as genes, drugs, cells or other biomolecules and how these revolutionary systems can complement existing therapeutic delivery systems. [ABSTRACT FROM AUTHOR]

Meniscus tissues have limited regenerative capacity once damaged. The treatment options for the meniscus tissue regeneration have been limited to arthroscopic meniscectomy or surgical interventions. The injectable hydrogels based system would provide an alternative to the conventional meniscus therapy by providing a minimally invasive treatment alternative. Here we utilized enzyme-based approaches to fabricate tissue adhesive hydrogels for meniscus repair. Tyramine (TA) conjugated hyaluronic acid (TA-HA) and gelatin are susceptible to tyrosinase (TYR)-mediated crosslinking in vitro and in vivo . Importantly, mechanical properties and degradation kinetics are modulated by the TA substitution and TYR concentrations. In addition, TYR −mediated crosslinking displayed tissue-adhesive properties. Furthermore, fibrochondrocyte-laden and TYR-crosslinked hydrogels demonstrated strong biocompatibility and resulted in enhancement of cartilage-specific gene expression and matrix synthesis. Overall, this represents a potential application of enzyme-mediated crosslinking hydrogels for meniscus tissue engineering. [ABSTRACT FROM AUTHOR]

A novel injectable methylcellulose (MC) hydrogel containing calcium phosphate nanoparticles (CaP NPs) was prepared by an in situ formation process, in which the precursor salts induced a salt-out effect in the MC solution. The thermo-sensitive properties of MC-CaP NPs composite hydrogels with different crystalline phases were characterized by rheometry, infrared spectroscopy and injectability test. The as-prepared MC hydrogels with bioactive CaP NPs had a suitable injectability at the body temperature, irrespective of the crystalline phases of CaP NPs. At the physiological pH condition, the structure of the MC hydrogel containing CaP NPs was analyzed by scanning electron microscopy, X-ray diffraction (XRD). The XRD results indicate that the in situ synthesized CaP NPs had a crystalline phase of hydroxyapatite (HAP). The in vitro study using mesenchymal stem cells showed that MC-HAP NPs composite hydrogel was biocompatible. The in vivo study indicated that the regeneration rate of new mature bone was also higher in the MC-HAP NPs composite hydrogel than in the pure MC hydrogel. The results of this study indicate that injectable MC-HAP NPs composite hydrogel has a great potential for bone tissue regeneration. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the localized osteogenic activity of recombinant human bone morphogenetic protein (rhBMP-2), when delivered using enzymatically crosslinkable injectable glycol chitosan hydrogel. A critical sized bilateral calvarial defect model was used wherein one defect was implanted with rhBMP-2 loaded hydrogel (HPP-GC + BMP). The neighboring defect was implanted with an osteoconductive, collagen hydroxyapatite matrix “Healos ® ”. The implantation of HPP-GC + BMP led to complete closure of the critical sized defect at 4 weeks post-implantation. The neighboring site implanted with Healos ® however, did not show any bone formation. The spatial control of rhBMP-2 bioactivity at the cellular level was confirmed by histological and histomorphometric analysis of the calvaria isolated from Col3.6 transgenic animals which can express fluorescence in osteoblast and pre-osteoblast cells. The retained rhBMP-2 in HPPGC + BMP implant was able to localize osteoprogenitor recruitment and osteogenesis, at the implantation site. The results demonstrate the efficacy of HPP-GC hydrogel in minimizing the diffusive loss of rhBMP-2 from the implantation site, compared to the collagen hydroxyapatite scaffold. [ABSTRACT FROM AUTHOR]

Overcoming bacterial infections and promoting wound healing are significant challenges in clinical practice and fundamental research. This study developed a series of enzymatic crosslinking injectable hydrogels based on silk fibroin (SF), carboxymethyl cellulose (CMC), and agarose, with the addition of polydopamine functionalized graphene oxide (GO@PDA) to endow the hydrogel with suitable conductivity and antimicrobial activity. The hydrogels exhibited suitable gelation time, stable mechanical and rheological properties, high water absorbency, and hemostatic properties. Biocompatibility was also confirmed through various assays. After loading the antibiotic vancomycin hydrochloride, the hydrogels showed sustained release and good antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The fast gelation time and desirable tissue-covering ability of the hydrogels allowed for a good hemostatic effect in a rat liver trauma model. In a rat full-thickness burn wound model, the hydrogels exhibited an excellent treatment effect, leading to significantly enhanced wound closure, collagen deposition, and granulation tissue formation, as well as neovascularization and anti-inflammatory effects. In conclusion, the antibacterial electroactive injectable hydrogel dressing, with its multifunctional properties, significantly promoted the in vivo wound healing process, making it an excellent candidate for full-thickness skin wound healing. [ABSTRACT FROM AUTHOR]

Drug-loaded injectable hydrogels have been studied widely in biomedical technology while the stable long-term controlled drug release and cytotoxicity are challenges. In this work, an injectable hydrogel with good swelling resistance was in situ synthetized using aminated hyaluronic acid (NHA) and aldehyde β-cyclodextrin (ACD) via Schiff base reaction. The composition, morphology and mechanical property were characterized with FTIR, 13C NMR, SEM and rheology test, respectively. Voriconazole (VCZ) and Endophthalmitis was selected as a model drug and disease, respectively. The drug release, cytotoxicity and antifungal properties were detected in vitro. The results showed a long-term (> 60 days) drug release was realized, the NHA/ACD2/VCZ presented a zero-order release in the later stage. The cytotoxicity of NHA/ACD was detected by live/dead staining assay and Cell Counting Kit-8 (CCK-8). The survival rate of adult retina pigment epithelial cell line-19 (ARPE-19) was over 100 % after 3 d, it indicated a good cytocompatibility. The antifungal experiment presented samples had antifungal property. Biocompatibility in vivo proved NHA/ACD2 had no adverse effects on ocular tissues. Consequently, the injectable hydrogel based on hyaluronic acid prepared by Schiff base reaction provides a new option for long-term controlled drug release in the course of disease treatment from a material perspective. [ABSTRACT FROM AUTHOR]

To resolve poor accumulation caused by systemic administration, injectable and responsive hydrogels are the prospective drug delivery systems for localized tumor treatment, owning to negligible invasiveness and accurate administration. Herein, an injectable hydrogel, based on dopamine (DA) crosslinked hyaluronic acid and Bi 2 Se 3 nanosheets (NSs) loading with doxorubicin (DOX) coated with polydopamine (Bi 2 Se 3 -DOX@PDA), was developed for synergistic chem-photothermal cancer therapy. The ultrathin functional Bi 2 Se 3 -DOX@PDA NSs could be responsive to the weak acidic condition and photothermal effect under NIR laser irradiation, achieving controlled release of DOX. Moreover, nanocomposite hydrogel based on hyaluronic acid matrix could be precisely administrated through intratumoral injection since its injectability and self-healing capacity, remaining at injected sites for at least 12 days. Furthermore, the excellent therapeutics effect of Bi 2 Se 3 -DOX@PDA nanocomposite hydrogel was demonstrated on 4 T1 xenograft tumor with outstanding injectability and negligible systemic side-effect. In short, the construction of Bi 2 Se 3 -DOX@PDA nanocomposite hydrogel paves a prospective path for local treatment of cancers. • An injectable and self-healing hydrogel was constructed for synergistic chemo-photothermal therapy. • 2D Bi 2 Se 3 nanosheets can release doxorubicin responsive to pH and NIR irradiation. • The injectable hydrogel was applied through intratumoral injection with minimal invasiveness compared with systemic administration. [ABSTRACT FROM AUTHOR]