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Breast cancer is a malignant tumor that poses a significant threat to women's health and single therapy fails to play a good oncological therapeutic effect. Synergistic treatment with multiple strategies may make up for the deficiencies and has gained widespread attention. In this study, sulfhydryl-modified hyaluronic acid (HA-SH) was covalently crosslinked with polydopamine (PDA) via a Michael addition reaction to develop an injectable hydrogel, in which PDA can be used not only as a matrix but also as a photothermal agent. After HSA and paclitaxel were spontaneously organized into nanoparticles via hydrophobic interaction, hyaluronic acid with low molecular weight was covalently linked to HSA, thus conferring effectively delivery. This photothermal injectable hydrogel incorporates PTX@HSA-HA nanoparticles, thereby initiating a thermochemotherapeutic response to target malignancy. Our results demonstrated that this injectable hydrogel possesses consistent drug delivery capability in a murine breast cancer model, collaborating with photothermal therapy to effectively suppress tumor growth, represented by low expression of Ki-67 and increasing apoptosis. Photothermal therapy (PTT) can effectively stimulate immune response by increasing IL-6 and TNF-α. Notably, the treatment did not elicit any indications of toxicity. This injectable hydrogel holds significant promise as a multifaceted therapeutic agent that integrates photothermal and chemotherapeutic modalities. [Display omitted] [ABSTRACT FROM AUTHOR]

Designing materials for wound dressings with superior therapeutic benefits, self-healing and injectable characteristics is important in clinical practice. Herein, a new self-healing injectable hydrogel was prepared via thermal treatment and dynamic Schiff base reaction by mixing oxidized hyaluronic acid (OHA) and hydrazided Salecan (Sal-ADH). The versatility of the wound dressing was confirmed by studying the inherent rheological properties, high swelling rate, sustained-release behavior of the drug, pH/hyaluronidase-dependent biodegradation, in vitro antimicrobial as well as in vivo wound healing performance. The presence of the antimicrobial drug polyhexamethylene biguanide (PHMB) conferred good antimicrobial properties to the Sal-ADH/OHA/PHMB (SOP) hydrogel, which could effectively prevent wound infection (the width of the inhibition circle of SOP-0.20 hydrogel was 4.97 mm, 5.93 mm for Staphylococcus aureus and Escherichia coli , respectively). The findings suggested that SOP hydrogel exhibited remarkable self-healing and injectability properties, as well as excellent hemostasis and biocompatibility. In vivo experiments indicated that the application of SOP hydrogels would obviously accelerate wound healing and attenuate the inflammatory response while increasing collagen deposition and angiogenesis. Altogether, antibacterial SOP hydrogels with moderate mechanical properties, pH-responsive release, excellent injectability, exceptional self-healing ability and anti-inflammatory effects could expand potential applications of injectable hydrogels in the biomedical field. [Display omitted] • The injectable hydrogel can form rapidly. • The hydrogel releases the antibacterial drug in acidic bacterial infections. • The hydrogel accelerates MRSA-infected wound healing without additions. • Hydrogels could participate in the entire wound healing process. [ABSTRACT FROM AUTHOR]

Skin wounds are susceptible to infection, leading to severe inflammatory reactions that can progress to chronic wounds, ultimately causing significant physical and mental distress to the patient. In this study, we propose an injectable composite hydrogel achieved through one-pot gelation of oxidized xyloglucan (OXG), cationic polyamide ε-poly-l-lysine (EPL), and surface amino-rich silicon nanoparticles (SiNPs). OXG exhibits commendable anti-inflammatory properties and provides crosslinking sites. SiNPs serve as mechanically reinforced crosslinkers, facilitating the construction of a dynamic Schiff base network. SiNPs significantly reduced the gelation time to 3 s and tripled the storage modulus of the hydrogels. Additionally, the combination of EPL and SiNPs demonstrated synergistic antimicrobial activity against both S. aureus and E. coli. Notably, the hydrogel effectively halted liver bleeding within 30 s. The hydrogel demonstrated outstanding shear-thinning and self-healing properties, crucial considerations for the design of injectable hydrogels. Furthermore, its efficacy was evaluated as a wound dressing in a mouse model with S. aureus infection. The results indicated that, compared to commercial products, the hydrogel exhibited a shorter wound healing time, decreased inflammation, thinner epithelium, increased hair follicles, enhanced neovascularization, and more substantial collagen deposition. These findings strongly suggest the promising potential of the proposed hydrogel as an effective wound dressing for the treatment of infected wounds. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [Display omitted] [ABSTRACT FROM AUTHOR]

Different types of clinical wounds are difficult to treat while infected by bacteria. Wound repair involves multiple cellular and molecular interactions, which is a complicated process. However, wound repair often suffers from abnormal cellular functions or pathways that result in unavoidable side effects, so there is an urgent need for a material that can heal wounds quickly and with few side effects. Based on these needs, hydrogels with injectable properties have been confirmed to be able to undergo self-healing, which provides favorable conditions for wound healing. Notably, as a biopolymer with excellent easy-to-modify properties from a wide range of natural sources, chitosan can be used to prepare injectable hydrogel with multifunction for wound healing because of its outstanding flowability and injectability. Especially, chitosan-based hydrogels with marked biocompatibility, non-toxicity, and bio-adhesion properties are ideal for facilitating wound healing. In this review, the characteristics and healing mechanisms of different wounds are briefly summarized. In addition, the preparation and characterization of injectable chitosan hydrogels in recent years are classified. Additionally, the bioactive properties of this type of hydrogel in vitro and in vivo are demonstrated, and future trend in wound healing is prospected. [Display omitted] [ABSTRACT FROM AUTHOR]

Our study aimed to introduce a novel double-cross-linked and thermoresponsive hydrogel with remarkable potential for accelerating third-degree burn wound healing. Burn injuries are recognized as challenging, critical wounds. Especially in third-degree burns, treatment is demanding due to extended wounds, irregular shapes, significant exudation, and intense pain during dressing changes. In this work, hydrogels made of zwitterionic chitosan and dialdehyde starch (ZCS and ZDAS) were created to deliver silymarine (SM) and levofloxacin (LEV). The hydrogels were effortlessly produced using dynamic Schiff base linkages and ionic interactions between ZCS and ZDAS at appropriate times. The pore uniformity, gel fraction, and commendable swelling properties can imply a suitable degree of Schiff base cross-link. The hydrogel demonstrated outstanding shape retention, and significant self-healing and flexibility abilities, enabling it to uphold its form even during bodily movements. After injecting biocompatible hydrogel on the wound, a notable acceleration in wound closure was observed on day 21 (98.1 ± 1.10 %) compared to the control group (75.1 ± 6.13 %), and histopathological analysis revealed a reduction of inflammation that can be linked to remarkable antioxidant and antibiotic properties. The results demonstrate the hydrogel's efficacy in promoting burn wound healing, making it a promising candidate for medical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

The intricate, hostile, and diverse nature of osteomyelitis (OM) poses a challenge for complete bacterial eradication and osteogenesis promotion via conventional treatment. Recently, functional hydrogels exhibiting antibacterial and osteogenic properties emerge as a promising avenue for OM wound healing in clinical practice. However, the preparation procedures and associated costs on cytokine and cell therapies for certain functional hydrogels can be complex and prohibitively expensive. In our research, a hybrid hydrogel dressing has been formulated utilizing carboxymethyl chitosan (CMCS) as the base material, and designed with inherent antibacterial, adhesion, proliferation, and differentiation characteristics, showing promise as a candidate for eradicating infection and promoting bone regeneration. The hybrid hydrogel is composed of interconnected networks of Fe3+-induced self-assembled CMCS and the antibacterial drug ciprofloxacin (CIP), resulting in excellent injectability and moldability. Notably, the CMCS/Fe3+/CIP hybrid hydrogel is capable of regulating antibacterial responses and stimulating osteogenesis in infected microenvironments without additional additives. This injectable antibacterial and osteogenic-promoting hydrogel establish a high-potential platform for low-cost, safe and effective treatment of OM by expediting the initial stages of infected bone wound repair. [Display omitted] [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Novel thermosensitive and degradable furyl-modified hydroxypropyl chitin synthesized. • Injectable and dually crosslinked hydrogel formed from thermogelation and DA reaction. • The dually crosslinked hydrogel showed improved strength than the physical thermogel. • This chitin-modified hydrogel with good biocompatibility useful for 3D cell culture. Abstract Injectable thermosensitive hydrogels crosslinked physically have been extensively studied as scaffolds in biomedical field, however, their low gel stability with weak strength limits their potential applications. Here, a novel thermosensitive furyl-modified hydroxypropyl chitin polymer was synthesized homogeneously in aqueous solution for developing injectable and dually crosslinked degradable hydrogel by integration of Diels−Alder click reaction using crosslinker maleimide-terminated PEG under physiological conditions. The dually crosslinked chitin-modified hydrogel showed much higher mechanical strength and slower biodegradation rate in contrast with the solely physically crosslinked thermosensitive hydroxypropyl chitin hydrogel. Cells encapsulated in the hydrogel displayed sustainable proliferation and good ability of self-assembling to form multicellular spheroids. In vivo investigation of the thermosensitive chitin-based dually crosslinked hydrogel showed favorable injectability, in-situ thermogelation and good biocompatibility. Thus the injectable, biodegradable and biocompatible dually crosslinked chitin-based hydrogel holds great potential for being applied in three dimensional cell culture and tissue repair. [ABSTRACT FROM AUTHOR]

In situ forming injectable hydrogels based on thermosensitive polymers are being investigated for tissue engineering applications. However, the major limitations of this kind of hydrogels are low gel stability and weak mechanical properties under physiological conditions. Here, thermosensitive hydroxypropyl chitin (HPCH) was synthesized homogenously and subsequently functionalized with photocrosslinkable methacrylate groups via glycidyl methacrylate to generate glycidyl methacrylate-modified HPCH (GM-HPCH). The obtained new GM-HPCH polymers exhibited similar reversible thermosensitive sol–gel transition behaviors at a low concentration (2 wt% in PBS). The physical thermogelation GM-HPCH hydrogels were able to be photocrosslinked by UV irradiation under physiological conditions to form enhanced stable and mechanically strong hydrogels. The mechanical property, swelling and degradation behavior of the hydrogels could be tuned by controlling the degree of substitution of methacrylate groups and UV exposure time. Cytotoxicity test displayed that the photocrosslinked thermogels were non-cytotoxic. The photocrosslinkable GM-HPCH thermogels hold great potential for biomedical applications. [ABSTRACT FROM AUTHOR]

Injectable hydrogels have been an attractive topic in biomaterials. However, during gelation in vivo, they are easy to disperse due to tissue exudates, thus leading to failure of controlled drug release. To solve this problem, we present a novel polysaccharide-based injectable hydrogel via self-crosslinking of aldehyde-modified xanthan (Xan-CHO) and carboxymethyl-modified chitosan (NOCC). The physical properties were optimized by adjusting the mass ratio of Xan-CHO and NOCC. Experiments revealed that this material exhibited the characteristics of self-healing, anti-enzymatic hydrolysis, biocompatibility and biodegradability. The releasing curve demonstrated stable release of BSA-FITC within 10 h after injection in liquids. After incorporation with a vascular endothelial growth factor, there was an interaction between this biomaterial and the host, which accelerated the reconstruction of the abdominal wall in rats. Therefore, this injectable hydrogel, as a drug delivery system, can prevent drug outburst in a variety of settings and function as a tissue scaffold. [ABSTRACT FROM AUTHOR]

The use of injectable hydrogel formulations have been suggested as a promising strategy for the treatment of degenerative disc disease to both restore the biomechanical function and reduce low back pain. In this work, a new thermo-sensitive injectable hydrogels with tunable thermo-sensitivity and enhanced stability were developed with N -hexanoylation of glycol chitosan (GC) for treatment of degenerative disc disease, and their physico-chemical and biological properties were evaluated. The sol-gel transition temperature of the hydrogels was controlled in a range of 23–56 °С, depending on the degree of hexanoylation and the polymer concentration. In vitro and in vivo tests showed no cytotoxicity and no adverse effects in a rat model. The hydrogel filling of the defective IVD site in an ex vivo porcine model maintained its stability for longer than 28 days. These results suggest that the hydrogel can be used as an alternative material for treatment of disc herniation. [ABSTRACT FROM AUTHOR]

TEMPO–oxidized cellulose nanofiber (TOCNF) is a natural material with many promising properties, including biocompatibility and degradability. In this study, we integrated TOCNF at different concentrations (0.2, 0.4, 0.6, 0.8% w/v) with chitosan (CS) and created a thermosensitive injectable hydrogel intended for biomedical applications. These hydrogels can undergo sol-gel transition at body temperature through interactions between chitosan and β-glycerophosphate. The addition of TOCNF resulted in faster gelation time and increased porosity. These hydrogels with TOCNF showed improved biocompatibility both in vitro and in vivo compared to CS hydrogel. Both MC3T3-E1 pre-osteoblast cells and L929 fibroblast cells showed biocompatibility towards CS/TOCNF 0.4. After 7 days of implantation, initial inflammatory response to CS/TOCNF 0.4 was found. Such response was significantly subsided within 14 days. Cell infiltration within the hydrogel was also prominent, showing anti-inflammatory or wound healing (M2) macrophage at 14 days after implantation. These results showed that the addition of TOCNF could significantly improve the biocompatibility of CS hydrogel as a biomaterial for biomedical application. [ABSTRACT FROM AUTHOR]

Injectable hydrogels have great potential in minimally invasive delivery. In this work, novel injectable hydrogels were prepared via self-crosslinking of aldehyde hyaluronic acid (HA-CHO) and hydrazide-modified poly (γ-glutamic acid) (γ-PGA-ADH) for proteins delivery. The HA/γ-PGA hydrogels could be formed in situ as fast as 9s with high swelling ratios. Rheological properties illustrated a wide processing range and good mechanical properties, which were reflected by broad linear viscoelastic region and higher threshold shear stress ( σ c ) and storage modulus ( G′ ). Meanwhile, the gelation time, swelling ratio, rheological properties, as well as the protein release behavior could be modulated conveniently. Bovine serum albumin (BSA) was designed as a model drug to study the release behavior. We found that the release mechanisms were either diffusion or Case-II relaxation depending on the different hydrogel components. The HA/γ-PGA hydrogels also showed good biocompatibility. Therefore, the HA/γ-PGA hydrogels have great potential as promising injectable biomaterials for controlled protein delivery. [ABSTRACT FROM AUTHOR]

Clinical wound management of combined radiation and burn injury (CRBI) remains a huge challenge due to serious injuries induced by redundant reactive oxygen species (ROS), the accompanying hematopoietic, immunologic suppression and stem cell reduction. Herein, the injectable multifunctional Schiff base cross-linked with gallic acid modified chitosan (CSGA)/oxidized dextran (ODex) hydrogels were rationally designed to accelerate wound healing through elimination of ROS in CRBI. CSGA/ODex hydrogels, fabricated by mixing solutions of CSGA and Odex, displayed good self-healing ability, excellent injectability, strong antioxidant activity, and favorable biocompatibility. More importantly, CSGA/ODex hydrogels exhibited excellent antibacterial properties, which is facilitated for wound healing. Furthermore, CSGA/ODex hydrogels significantly suppressed the oxidative damage of L929 cells in an H 2 O 2 -induced ROS microenvironment. The recovery of mice with CRBI in mice demonstrated that CSGA/ODex hydrogels significantly reduced the hyperplasia of epithelial cells and the expression of proinflammatory cytokine, and accelerated wound healing which was superior to the treatment with commercial triethanolamine ointment. In conclusion, the CSGA/ODex hydrogels as a wound dressing could accelerate the wound healing and tissue regeneration of CRBI, which provides great potential in clinical treatment of CRBI. [Display omitted] • Novel injectable CSGA/ODex hydrogels were prepared by cross-linking based on Schiff base. • CSGA/ODex hydrogels exhibited the excellent antibacterial, ROS scavenging and anti-inflammation properties. • The multifunctional CSGA/ODex hydrogels could accelerate wound healing in combined radiation and burn injury. [ABSTRACT FROM AUTHOR]

Injectable stimuli-responsive hydrogels could offer an opportunity for local administration at the tumor site and a sustained drug release. In this paper, a copolymer of azobenzene derivative and N-isopropyl acrylamide (NIPAM) was synthesized, which are performed as light- and thermo-sensitive parts, respectively. The DAS@SCD/NIPAZO hydrogel was prepared upon the establishment of host-guest interactions between the hydrophobic core of CD and azobenzene moiety. The LCST of the synthesized copolymer was modified from 31.3 °C to 36.5 °C by the incorporation of the hydrophilic host moieties of the modified starch into the NIPAM copolymer structure. The LCST-based property of the hydrogel made it syringable in low temperatures and switch to a gel state after local injection. The drug release profile of the hydrogel was explored in four different conditions involving two distinct temperatures combined with two different light wavelengths to examine the light- and thermo-sensitivity of the hydrogel. Moreover, a Paclitaxel-loaded hydrogel was prepared to study the in vitro efficiency of the sample and was investigated by MTT assay against the cancerous fibroblastic cells (A-431), which revealed a sharp decline in cell viability under 365 nm light irradiation; furthermore, to evaluate the in vivo effects of the PTX-loaded hydrogel, histological studies based on staining techniques were carried out. [ABSTRACT FROM AUTHOR]

Bone disease is a public health problem around the word, and it is urgent to develop novel tissue engineering scaffolds for the complicated cranial bone regeneration. The present work developed a novel triple crosslinked polysaccharides based injectable hydrogel to composite bio-glass (BG) for cranial bone repair. Dynamic mechanical analysis showed the storage modulus (G′) of the hydrogel reached to ∼4000 Pa. While after compositing BG, G′ exceeded 4500 Pa. The degradation behavior of the hydrogel is influenced by hydrogel composition, crosslinking methods and degradation environment. Through compositing BG for rat cranial bone repair, excellent bone regeneration effect was achieved (chunks of “white” new tissue was detected in the defected site, HE histopathological analysis confirmed the new tissue was bone tissue). Thus, the hydrogel is suitable as the carrier of BG for bone repair, demonstrating the prepared triple crosslinked hydrogel is potential for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

This paper reports injectable hyaluronic acid (HA)-based hydrogels crosslinked with azide-modified poly(ethylene glycol) (PEG) via the strain-promoted azide–alkyne cycloaddition (SPAAC) between cyclooctyne and azide groups. Cyclooctyne-modified HA (Cyclooctyne-HA) is prepared by the reaction of HA with 2-(aminoethoxy)cyclooctyne. To crosslink the modified HA, quadruply azide-terminated poly(ethylene glycol) (Azide-PEG) is designed and prepared. The mixture of Cyclooctyne-HA and Azide-PEG gelates in a few minutes to form a strong HA-PEG hydrogel. The hydrogel has fast gelation time, good strength, and slow degradation rate, because of the high reactivity of SPAAC, high crosslinking density originated from the quadruply-substituted Azide-PEG, and the good stability of the crosslinking amide bonds. In vitro cell culturing within the hydrogel demonstrated an excellent cell-compatibility. The bioorthogonality of SPAAC makes the hydrogel injectable. With good mechanical properties and biocompatibility, the hydrogel would be useful in a wide range of applications such as injection filling materials for plastic surgery. [ABSTRACT FROM AUTHOR]

In the present study, we developed a biomimetic injectable hydrogel system based on hyaluronic acid-adipic dihydrazide and the oligopeptide G 4 RGDS-grafted oxidized pectin, in which their hydrazide and aldehyde-derivatives enable covalent hydrazone crosslinking of polysaccharides. The hydrazone crosslinking strategy is simple, while circumventing toxicity, making this injectable system feasible, minimally invasive and easily translatable for regenerative purposes. By varying their weight ratios, the physicochemical properties of the mechanically stable hydrogel system were easily adjustable. Additionally, the preliminary studies demonstrated that chondrocyte behavior was dependent on HA/pectin composition and the presence of integrin binding moieties. Specifically, the incorporation of a certain amount of G 4 RGDS oligopeptide into HA/pectin-based hydrogels could serve as a biologically active microenvironment that supported chondrocyte phenotype and facilitated chondrogenesis. Furthermore, the hydrogel system exhibited acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable multicomponent hydrogel presented here is expected to be useful biomaterial scaffold for cartilage tissue regeneration. [ABSTRACT FROM AUTHOR]

In the present work, a thermosensetive copolymer with a low gelation concentration under 37 °C, F127@ChS (F127 crosslinked chondroitin sulfate) was synthesized via DA click chemistry between F127-AMI (maleimido terminated F127) and ChS-furan (furfurylamine grafted chondroitin sulfate). Then, dual crosslinked hydrogels were prepared based on F127@ChS and PEG-AMI (maleimido terminated polyethylene glycol). The physical crosslinking of F127@ChS affords the hydrogel fast gelation behavior, while in situ DA click reaction occurred between F127@ChS and PEG-AMI affords the hydrogel system covalent crosslinking. The dual crosslinked injectable hydrogel was applied as scaffold to load BMP-4 for rat cranial defect repair. As indicated by X-ray imaging, cranial digital images and histological (HE and Masson) staining analysis, new bone tissues were formed in the defected area after 12 weeks repair. The results demonstrate that the novel dual crosslinked injectable hydrogel offer an interesting option for cranial bone tissue engineering. [ABSTRACT FROM AUTHOR]

Photocrosslinked hydrogels are being investigated for many tissue engineering applications because of the ability to form these materials in-situ in a minimally invasive manner by injection of aqueous solution under physiological conditions. In this work, carboxymethyl chitin (CMCH) synthesized homogenously was further modified with methacrylic anhydride and photocrosslinked into hydrogel with tunable degradation and mechanical properties. This new methacrylated carboxymethyl chitin (Me-CMCH) hydrogel formed in-situ photocrosslinked under UV irradiation showed much higher storage modulus than that of the thermosensitive in-situ forming physical-crosslinking CMCH hydrogel. The Me-CMCH hydrogels remained stable under physiological conditions and could be degraded by lysozyme. Cytotoxicity test indicated that the photo-induced Me-CMCH hydrogels were non-cytotoxic. The mechanical property, morphology, swelling and biodegradation behavior of the Me-CMCH hydrogels could be tuned by controlling the degree of methacrylation of Me-CMCH. These biodegradable photocrosslinkable Me-CMCH hydrogels may hold great promises for various biomedical applications. [ABSTRACT FROM AUTHOR]

Injectable hydrogel is of interesting for wound healing due to it can be used as carriers of bioactive molecules for the reparation of tissues with minimal invasiveness. However, the integration of lipid-soluble substances into hydrogel network is difficult because of the polarity differences. Here, the tea tree oil (TTO) is encapsulated into the hydrogel network via a previous emulsification process, and a tough and antibacterial injectable hydrogel is synthesized by the Schiff base reaction between carboxymethyl chitosan (CMCS) and genipin (GP). CMCS is served as both an emulsifier and a gel-forming material to construct the heterogeneous hydrogel. The obtained hydrogels present high adhesive strength (∼162.75 kPa), great antibacterial properties (over 90 %) and excellent biocompatibility. Moreover, an anal fistula-like wound healing experiment concluded that the heterogeneous hydrogel has good slow-release properties of TTO for an accelerate healing process, this hydrogel shows great potential for the treatment of complex anal fistula wounds. [Display omitted] [ABSTRACT FROM AUTHOR]

Injectable hydrogels effectively remodel degenerative nucleus pulposus (NP) with a resemblance to the in vivo microenvironment. However, the pressure within the intervertebral disc requires load-bearing implants. The hydrogel must undergo a rapid phase transition upon injection to avoid leakage. In this study, an injectable sodium alginate hydrogel was reinforced with silk fibroin nanofibers with core-shell structures. The nanofiber-embedded hydrogel provided support to adjacent tissues and facilitated cell proliferation. Platelet-rich plasma (PRP) was incorporated into the core-shell nanofibers for sustained release and enhanced NP regeneration. The composite hydrogel exhibited excellent compressive strength and enabled leak-proof delivery of PRP. In rat intervertebral disc degeneration models, radiography and MRI signal intensities were significantly reduced after 8 weeks of injections with the nanofiber-reinforced hydrogel. The biomimetic fiber gel-like structure was constructed in situ , providing mechanical support for NP repair, promoting the reconstruction of the tissue microenvironment, and finally realizing the regeneration of NP. [Display omitted] [ABSTRACT FROM AUTHOR]

Oxidative stress and inflammation are common pathological mechanisms for the progression of tissue degeneration. Epigallocatechin-3-gallate (EGCG) features antioxidant and anti-inflammatory properties, which is a promising drug for the treatment of tissue degeneration. Herein, we utilize the phenylborate ester reaction of EGCG and phenylboronic acid (PBA) to fabricate an injectable and tissue adhesive EGCG-laden hydrogel depot (EGCG HYPOT), which can achieve anti-inflammatory and antioxidative effects via smart delivery of EGCG. Specifically, the phenylborate ester bonds, formed by EGCG and PBA-modified methacrylated hyaluronic acid (HAMA-PBA), endow EGCG HYPOT injectability, shape adaptation and efficient load of EGCG. After photo-crosslinking, EGCG HYPOT exhibits good mechanical properties, tissue adhesion and sustained acid-responsive release of EGCG. EGCG HYPOT can scavenge oxygen and nitrogen free radicals. Meanwhile, EGCG HYPOT can scavenge intracellular reactive oxygen species (ROS) and suppress the expression of pro-inflammatory factors. EGCG HYPOT may provide a new idea for alleviation of inflammatory disturbance. [Display omitted] [ABSTRACT FROM AUTHOR]

Homogenous modification of natural chitin offers the advantage of fair structure control. In this work, novel carboxymethyl chitins (CMCHs) with broad range of degree of substitution (DS: 0.035 to 0.74), high degree of acetylation (DA) and little de-polymerization were synthesized homogeneously in aqueous NaOH/urea solution. The simultaneous determination of DA, DS and carboxymethylation fraction at C3 and C6 for these CMCHs was achieved by proton NMR in acidic deuterated aqueous solution for the first time. Due to the good homogeneity, the prepared CMCH-4 with lower DS of carboxymethylation exhibited, for the first time to our knowledge, dual thermo- and pH-sensitive properties. The nontoxic thermo-sensitive polymer systems gel at body temperature (37 °C) in physiological condition, which is very useful as injectable hydrogels for drug delivery and tissue engineering. [ABSTRACT FROM AUTHOR]

The aim of the current study was to enhance the mechanical property of chitosan/β-glycerophosphate disodium salt (CS/GP) injectable hydrogels. A novel nanocomposite injectable hydrogel was prepared by introducing attapulgite (ATP) nano particles into the CS/GP hydrogels. The mechanical properties of the composite hydrogels with two different water contents were characterized by tensile test, the results shown that the tensile strength and elongation at break of composite hydrogels both increased obviously with increasing of ATP content. And, in our testing range, the maximum values of tensile strength and elongation at break were both more than 5 times larger than that of neat CS/GP hydrogel. We discussed this enhancement effect in detail by Scanning electron microscope observations (SEM) and Fourier transform infrared spectroscopy testing (FT-IR). The SEM images of composite hydrogels shown quite different from the neat CS/GP hydrogel, where the pores were more tightly and with some uniform and smaller holes dispersed on the wall. FT-IR test results revealed that the introduction of ATP increased the cross-link density because of the hydrogen bonds formation between ATP nanoparticles and CS molecules. Also, we studied the impact of ATP introduction on gelation speed through tracking the dynamic process of the sol–gel transition by means of rheological measurement, and the results shown that the reaction rate increased significantly with the increase of ATP concentration. [ABSTRACT FROM AUTHOR]

In this article a novel bio-injectable algin-aminocaproic acid (Alg-ACA) tri-stimuli responsive thixogel system is reported. The designed soft thixotrophic hydrogel (thixogel) was characterized using various analytical techniques such as FT-IR, NMR, SEM, AFM and DSC. The soft thixogel system was further investigated for stress responsiveness using different rheological studies which confirmed the thixotropic nature of the gel [Thixotropic area ( A r ) of Alg-ACA (1:0.5), Alg-ACA (1:1) and Alg-ACA (1:2), were 23.5%, 43.1%, and 27.59%, respectively, which were higher than that of Na-Alg (2.08%)]. The thixogel also demonstrated temperature and ultrasonication responsiveness. This tri-stimuli responsive soft thixogel system was rendered flowable (fluid) on applying the described physical stimuli and recovered its “rigid” gel structure upon removal of the applied stimuli. This approach of synthesizing a thixogels may be applicable to a broad variety of other natural polymers and has the potential for use in biomedical applications. [ABSTRACT FROM AUTHOR]

Herein, an injectable self-healing hydrogel with inherent antibacterial activity was fabricated based on the dynamic covalent bond formation between boronic acid and catechol groups in quaternized chitosan as building blocks in conjunct with the in-situ encapsulation of epigallocatechin-3-gallate (EGCG, a green tea derivative). Benefiting from the catechol groups and therapeutic effect of EGCG, the resulting natural-based injectable hydrogels showed excellent antibacterial and antioxidant dual functions in preventing bacterial infection and scavenging radicals. The hydrogels loaded with EGCG also exhibited good biocompatibility along with contact-active antibacterial activity via a "capture and kill" strategy. The dynamic covalent bonding enables shear-thinning delivery of the gels via syringe, followed by rapid self-healing. Additionally, the in vivo wound healing evaluation in a full-thickness skin defect model revealed the appreciable and regenerative wound healing performance of the hydrogels, demonstrating their great potential as novel wound dressings for wound management. [Display omitted] [ABSTRACT FROM AUTHOR]

Injectable hydrogel precursor solution was prepared by physical blend of xanthan gum (XG) and methylcellulose (MC) in aqueous solution. Due to the formation of XG network composed of XG double helical strand structure, XG/MC blend was a high viscous solution with good shear-thinning property at room temperature. When the temperature was changed from 23 to 37 °C, thermo-responsive MC network formed, which caused XG/MC blend solution to gelate. The gelation time and storage modulus of the blend can be tuned by XG and/or MC concentrations. Both in vitro and in vivo investigations revealed that the blend solution immediately recovered its high viscosity and rapidly formed hydrogel at body temperature after injection using a syringe. In vivo biocompatibility and biodegradability of the hydrogel were validated by implantation of the hydrogel in rats. In vitro investigation demonstrated that XG/MC blend is a promising injectable hydrogel material for long-term drug delivery. [ABSTRACT FROM AUTHOR]

The use of injectable hydrogels is presently limited by the difficulty to achieve rapid gelation, high mechanical resistance and excellent cytocompatibility. In our study, high-strength injectable thermosensitive hydrogels of unmodified chitosan (CH) were obtained by combining sodium hydrogen carbonate (SHC) with phosphate buffer (PB) or beta-glycerophosphate (BGP) as gelling agents. A synergic effect led to the acceleration of gelation and a remarkable improvement of the storage modulus ( G ′) of the hydrogels. Furthermore, the new hydrogels exhibited drastically enhanced Young moduli and resistance in compression as compared to conventional hydrogels prepared with BGP, PB or their combination. This was achieved while reducing the total salt concentration in the hydrogels. The gelation was rapid and the hydrogels presented porous structures and physiological pH, and did not show any cytotoxicity to L929 fibroblast cells in vitro . Overall, these new hydrogels provide interesting alternatives for use as blood vessel embolizing agents or as injectable scaffolds for drug delivery and/or cell seeding in tissue engineering strategies. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) is characterized by low pH, hypoxia, and infiltrated tumor-associated macrophages (TAMs). Therefore, regulation of TAMs polarization into anti-tumor M1 phenotype and meanwhile alleviation of the hypoxia in TME are expected to improve anti-tumor therapeutic efficacy. To this end, a novel in situ injectable nano-complexed hydrogel was developed in this study for combining tumor therapy. Thereunto, hyaluronic acid modified transfersomes loaded with chlorogenic acid functioned to reverse M2 type into M1 type via CD44 mediated internalization, the nanomedicine was entrapped in Schiff-based crosslinked injectable hydrogel (fabricated with carboxymethyl chitosan and oxidized dextran) whose linkage was labile to the acidic TME for controlled drug release. Moreover, catalase was integrated in the hydrogel enabling to convert hydrogen peroxide in TME into dissolved oxygen and alleviate tumor hypoxia. The multifunctional nano-complexed injectable hydrogel was verified to efficiently inhibit tumor growth through synergetic effects of hypoxia alleviation and TAMs polarity regulation. [Display omitted] [ABSTRACT FROM AUTHOR]

Cellulose nanomaterials have received significant interest due to their superior physicochemical properties and biocompatibility. The nanomaterials-based hydrogel patches are widely explored for skin regeneration. However, the injectability and adhesiveness of the hydrogels are crucial challenges for tissue engineering applications. To overcome these, we synthesized an injectable and adhesive hydrogel of spherical nanocellulose (s-NC) reinforced carboxymethyl chitosan for rapid skin regeneration. The s-NC exhibited improved cellular activity than cellulose nanocrystals. The hydrogels exhibited adhesive and injectability potentials and were molded in the desired configurations. An enhanced conductivity was observed in s-NC added hydrogels than the pure polymer hydrogel. The skin regeneration potential of the hydrogel scaffolds was also examined in the rats using the wound healing model. The composite scaffolds also showed improved antibacterial potential. Taken together, the developed hydrogels have the potential and can be explored as a promising biomaterial for enhanced skin regeneration applications. [Display omitted] • Spherical nanocellulose (s-NC) added hydrogels exhibited ~85% recovery strength. • Synthesized hydrogels exhibited injectable and adhesive properties. • The s-NC exhibited enhanced cellular activity than cellulose nanocrystals (CNCs). • Enhanced skin cells proliferation was observed in s-NC loaded hydrogel. • Improved wound healing occurred in s-NC loaded scaffolds than polymer scaffold. [ABSTRACT FROM AUTHOR]

The poly(3-hydroxybutyrate) (PHB) organogel monoliths were prepared by nonsolvent-induced phase separation (NIPS). The NIPS-derived organogels were solvent-exchanged with chitosan (CS) solution, resulting in the successful loading of CS into PHB hydrogel. With increasing the CS content, the as-prepared composite hydrogels became syringe injectable with excellent thixotropy due to the increase in the gel network's hydrophilicity. The hydrogels were successfully freeze-dried into PHB/CS composite aerogels, which exhibited remarkably improved compressive modulus/collapse strength of 1.6 MPa/159 kPa compared to 0.5 MPa/31 kPa for pure PHB aerogels. The effect of CS on gel crystallization and structure was also investigated. The amphiphilic PHB/CS hydrogels effectively entrapped both hydrophilic/cationic doxorubicin (DOX) and hydrophobic/anionic indomethacin (IDM). The drug release behavior depended on the charge interactions between drugs and CS. The accelerated DOX release in acidic condition from injected hydrogels owing to the charge repulsion shows potential for a controlled and localized cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Prepared hydrogel based on reversible dynamic covalent and hydrogen bond synergic cross-linking. • Hydrogel have adjustable rheological and mechanical properties. • The obtained hydrogels are injectable, self-healing, self-recovering and fatigue resistance. • Biocompatible hydrogels support cell growth and proliferation. • Hydrogels as controlled-release carriers can be placed in the body in a more controlled manner. [ABSTRACT FROM AUTHOR]

Self-healing hydrogels with biodegradability have great potential biomedical application in drug loading and delivery, wound dressing and tissue engineering. In this research, biodegradable hydrogels were designed from oxidized CMC (CMC-CHO) and PEO 23 dinaphthoate hydrazide (PEO 23 DNH) with naphthalene structure for potential bio-imaging purpose. Results showed that the gelation time of this self-healing hydrogels was very fit for in situ injectable applications for drug loading and controlled release. The hydrogels also showed excellent biocompatibility because all the components and the acylhydrazone bond are biocompatible. Moreover, the in vitro and in vivo drug release study revealed the CMC-CHO based hydrogels could reduce the acute toxicity of the drugs with a controlled and sustained release manner. The hydrogel also showed hemostatic activity by sealing effect and mEGF loaded hydrogel accelerated the wound repairing efficacy. All above result proved the CMC-CHO/PEO 23 DNH hydrogel with luminescent property have great application property in bioscience and biotechnology. [Display omitted] • Self-healing hydrogel with light emission property was fabricated from CMC-CHO and PEO23 DNH. • The hydrogel showed excellent biocompatibility and biodegradability both in vitro and in vivo. • The hydrogel showed sustained drug release behavior, tissue adhesion and hemostasis activity. • The mEGF loaded hydrogel accelerated the wound repairing rate of the model mice. [ABSTRACT FROM AUTHOR]

Developing an efficient and available material for improved cutaneous tissue regeneration is a major challenge in healthcare. Inspired by the concept of moist wound healing, the injectable and self-healing adenine-modified chitosan (AC) hydrogels are designed to significantly accelerate wound healing without the addition of therapeutic drugs. A series of AC derivatives with degree of substitution (DS) ranging from 0.21 to 0.55 were synthesized in aqueous solutions, and the AC hydrogels were prepared by a simple heating/cooling process. AC hydrogels presented good self-healing, low swelling rate capacity, biocompatibility, promote cell proliferation and excellent hemostatic effect. The hydrogels displayed excellent antibacterial activities against gram-negative bacteria, gram-positive bacteria, fungi and drug-resistance bacteria. Moreover, the full-thickness skin defect model experiments showed that AC hydrogels could reduce inflammatory cell infiltration and accelerate wound healing significantly. The hydrogel can shed new light on designing of the multifunctional dressings for wound healing. [Display omitted] • Injectable, self-healing physically crosslinked chitosan hydrogels were designed. • Hydrogels had antibacterial activity and promoting cell proliferation activity. • Hydrogels exhibited good hemocompatibility and hemostatic properties. • Hydrogels with high degree of substitution significantly accelerated wound healing. [ABSTRACT FROM AUTHOR]

Injectable hydrogels have shown therapeutic effects on wound repair, but most of them exhibit poor mechanical strength. The impacts of stiff injectable hydrogels on cell behavior and wound healing remain unclear. Herein, an injectable hydrogel was developed based on thiolated poly(γ-glutamic acid) (γ-PGA-SH) and glycidyl methacrylate-conjuated oxidized hyaluronic acid (OHA-GMA). Thiol−methacrylate Michael chemistry-mediated post-stabilization and increase of polymer concentration were found to improve the mechanical strength of γ-PGA-SH/OHA-GMA hydrogel. Moreover, in vitro studies confirmed its biodegradability, biocompatibility, and self-healing property. Using the mechanically-tunable hydrogel, it further showed that fibroblasts migrated faster on the surface of stiffer hydrogel, but infiltrated slowly inside it compared with softer hydrogel. In animal experiments, the injectable hydrogel could promote wound healing by increasing collagen deposition and vascularization. In summary, γ-PGA-SH/OHA-GMA hydrogel is able to regulate migration and infiltration of fibroblasts by altering stiffness and offers effective in situ forming scaffolds towards skin tissue regeneration. • Thiolated γ-PGA and oxidized methacrylated HA are successfully synthesized. • The injectable HA/γ-PGA hydrogel can realize post-stabilization as needed. • The hydrogel can regulate fibroblast migration by tailoring the stiffness. • The hydrogel shows better effects on promoting wound repair than commercial film. [ABSTRACT FROM AUTHOR]

To meet the rising demand of injectable hydrogels with self-healing, robustness and biocompatibility for biomedical engineering, the reversible ketoester-type acylhydrazone linkages was used for the fabrication of novel cellulose-based hydrogel. The ketoester-type acylhydrazone bond exchanged rapidly, endowing the hydrogels with highly efficient self-healing performance without any external stimuli under physiological environment, which was hardly achieved with the widely used arylhydrozone bond. The dynamic hydrogels exhibited tunable mechanical property, pH responsiveness, injectability and biocompatibility, demonstrating immense applications prospect for various biomedicines, such as drug and cell delivery. The pH-responsive controlled release of model drug doxorubicin (DOX) loaded in the hydrogel was demonstrated. In addition, benefitting from the excellent biocompatibility and the reversible ketoester-type acylhydrazone bonds, cells were encapsulated in the hydrogels as 3D carrier. The covalent adaptable network intensified injectability of cell-laden hydrogels and improved the long-lasting viability for cell culture, showing great potential in the biomedical field. The ketoester-type acylhydrazone bond hydrogels are dressed with fast self-healing performance, robust mechanical properties, pH-responsibility, biocompatibility and shear-thinning behaviors. The superior self-healing property was attributed to the dynamic network generated through the reversible ketoester-type acylhydrazone bonds via acylhydrazide and ketoester groups without any external intervention, which was dominated by the kinetics of the reaction. Besides, the hydrogels are regarded as an ideal candidate for effective drug carrier due to its excellent injectability and pH-responsive behavior. Due to the excellent biocompatibility, cells remained good viability even after injecting the cell loaded hydrogel after 3D encapsulation. The present work supplied a biocompatible self-healing hydrogel with high performances, long-life service and minimally invasion, in the field of biomedical engineering. [Display omitted] • Injectable cellulose hydrogels were engineered via dynamic ketoester-type acylhydrazone crosslinkers. • The hydrogels had highly efficient self-healing performance without any external stimuli under physiological environment. • The hydrogels exhibited tunable mechanical property, pH responsiveness, injectability and biocompatibility. • The dynamic network could support 3D cell encapsulation and enhanced injectability of cell-laden hydrogels. [ABSTRACT FROM AUTHOR]

• DMEM-induced phenylboronic acid-modified hyaluronic acid hydrogels were developed. • The injectable hydrogel had good self-healing properties and tissue adhesion. • DMEM create a physiological PH environment and uniform nutrients for the cells. • The hydrogel was capable of supporting cell loading and proliferation. Most of traditional injectable hydrogels based on light curing or enzyme crosslinking are difficult to control the crosslinking time accurately and lack tissue adhesion, which leads to difficult clinical application and poor tissue repair effect. In this study, a novel injectable DMEM (Dulbecco's Modified Eagle's Medium)-induced phenylboronic acid-modified hyaluronic acid self-crosslinking hydrogel was designed and prepared by combining the phenylboronic acid and a diol on hyaluronic acid as the main network, in which dynamically reversible phenylboronic acid esters imparted good self-healing properties and tissue adhesion properties to the hydrogels. Cell medium that induced the formation of the hydrogel could simulate the pH of the physiological environment and provide uniform nutrients for the encapsulated cells. In addition, in vitro cell experiments indicated that the DMEM-induced phenylboronic acid-modified hyaluronic acid self-crosslinking hydrogel was capable of supporting cell loading and proliferation, thus being a promising candidate for tissue repair materials. [ABSTRACT FROM AUTHOR]

• Sulfhydryl modified hyaluronic acid (HA-SH) was synthesized. • DMSO as oxidant participated in disulfide bond crosslink of HA-SH to form hydrogel. • The dissolved drugs in DMSO were loaded inside the hydrogel during the crosslinking. • The drug loaded hydrogel can be used as injectable paratumoral implant. • The implant can sustained release the loaded drugs to suppress the tumor growth. Dimethyl sulfoxide (DMSO) is an excellent solvent for various types of anticancer drugs. Here, beyond that, it can participate in a disulfide bond crosslink between sulfhydryl (-SH) modified hyaluronic acid (HA-SH) molecules to form the hydrogel. Thus, during the above crosslink process, the dissolved drug in DMSO could be effectively loaded inside the hydrogels' porous structures as an injectable peritumoral implant. The loaded drugs can be sustained released through hydrogel swelling and degradation around the tumor tissue to suppress tumor growth. In this paper, the above hydrogel was used as a peritumoral drug-loaded implant for chemotherapeutics, photosensitizer, and photothermal reagent, respectively, for chemotherapy, photodynamic therapy, and photothermal therapy in cancer treatment. Therefore, this DMSO involved HA-SS-HA (HA, hyaluronic acid; -SS-, disulfide bond) hydrogel fabrication method is simple and widely applicable for drug-loaded peritumoral implant preparation. [ABSTRACT FROM AUTHOR]

• UV crosslinkable and injectable pentenyl chitosan (PTL-CS) was designed and synthesized by one-step N-acylation reaction. • PTL-CS hydrogel exhibited nonswelling via UV crosslinking induced hydrophobic effect. • PTL-CS was applied as patterned microgels and in situ forming hydrogel in vivoin minimally invasive therapy. Injectable chitosan hydrogels exhibit excellent biological properties for application in biomedical engineering, however most of these hydrogels have limited applicability because "Swelling" can induce volume expansion of conventional hydrogels implanted in the body damages the surrounding tissues. Here, we report a new "Nonswelling" pentenyl chitosan (PTL-CS) hydrogel via N‒acylation reaction to graft an UV crosslinkable short hydrophobic alkyl chain (n ‒pentenyl groups). The incorporated pentenyl groups can be crosslinked by UV irradiation to form hydrophobic chains via combination termination, which generate strong hydrophobic effect to extrude the excess water in hydrogel, resulting in a "Nonswelling" state at biological temperature. Furthermore, the PTL-CS solution showed no cytotoxicity in vitro and minimally invasive treatment in vivo demonstrated the PTL-CS hydrogel no adverse effects in a rat model. The nonswelling injectable and UV crosslinkable chitosan hydrogel hold potential applications in smart biomaterials and biological engineering as well as providing a new natural hydrogel in minimally invasive tissue engineering.. [ABSTRACT FROM AUTHOR]

• Synthesis of thermal- and photo-crosslinkable hydroxybutyl methacrylated chitosan. • Temperature and light can be used to control the crosslink density of chitosan hydrogel. • Mechanical and biochemical optimization possible by adjusting crosslinking density. • Injection of hydroxybutyl methacrylated chitosan solution into mice successfully forms hydrogels without incision. • In vivo forming HBC-MA hydrogels for injectable hydrogel applications. Thermo-sensitive injectable hydrogels that spontaneously react to physiological temperature have been widely studied to be used in biomedical fields. However, several challenges on their unstable structures with large-sized pores and low mechanical strength under physiological conditions must be addressed to enable their practical applications. We synthesized the hydroxybutyl methacrylated chitosan (HBC-MA) hydrogel that possesses both thermo-sensitive and photo-crosslinkable properties. The HBC-MA showed effective sol-gel transition under physiological temperature as well as a sensitive photo-crosslinkable property with visible light capable of skin penetration. The co-nonsolvency property and thermo-sensitivity of HBC-MA prevented unintended loss of the hydrogel graft after being subcutaneously injected in mice. Subsequently applied visible light on the skin beneath which the hydrogel was injected significantly improved the mechanical strength and stability of the graft. The injectable HBC-MA hydrogel developed in this study can be applicable to a wide range of biomedical fields such as drug delivery system and tissue engineering. [ABSTRACT FROM AUTHOR]

• Injectable AP-OC hydrogel was in-situ crosslinked without any chemical crosslinker. • Both of modified natural-polysaccharides were soluble in neutral solution. • Swelling and degradation property of AP-OC hydrogel can be tuned by its composition. • Amino site content in the hydrogel was crucial for good biocompatibility. • Hydrogel had desired gelation time and good biocompatibility for skin wound healing. Hydrogel can provide a favorable moisture environment for skin wound healing. In this study, a novel in-situ crosslinked injectable hydrogel was prepared using the water-soluble amidated pectin (AP) and oxidized chitosan (OC) through Schiff-base reaction without any chemical crosslinker. The influence of AP content on the properties of the hydrogel was systemically investigated. It showed that gelation time, pore structure, swelling capability and degradability of the hydrogel can be tuned by varying the content of amine and aldehyde groups from AP and OC. All the porous hydrogels with various AP contents (65%, 70%, and 80%) presented desirable gelation time, swelling property, high hemocompatibility and biocompatibility. Particularly, AP-OC-65 hydrogel presented superior swelling capability and better hemo- and bio-compatibility, owing to more residual amine sites in the hydrogel. Therefore, the injectable AP-OC-65 hydrogel has a greater potential for application to wound dressing or skin substitute. [ABSTRACT FROM AUTHOR]

• Chitosan was co-crosslinked with β-glycerol phosphate disodium salt (β-GP) and genipin. • β-GP content was widely varied to analyze its influence on the properties of the gels. • The loading and release of diclofenac was studied for the prepared hydrogels. Thermosensitive hydrogels based on polysaccharides are suitable candidates for the design of biodegradable and biocompatible injectable drug delivery systems. Thus, the combination of chitosan (CHI) and β-glycerol phosphate disodium salt (β-GP) has been intensively investigated to develop thermo-induced physical gels. With the aim of exploring the possibilities of optimization of these hydrogels, in this work, chitosan, β-GP and naturally extracted crosslinking agent, genipin (GEN), have been successfully combined, obtaining co-crosslinked hydrogels with both in situ physical and covalent crosslinking. A wide range of β-GP concentrations have been selected in order to analyze its influence on a variety of properties, including gelation time, pore size, water uptake ability, in vitro hydrolytic and enzymatic degradation, mucoadhesion and mechanical and rheological properties. Furthermore, the potential application of the developed systems for the administration and controlled release of an anti-inflammatory anionic drug, such as diclofenac, has been successfully demonstrated. [ABSTRACT FROM AUTHOR]

• Chitosan modified by and protocatechuic acid could act as antimicrobial and adhesive agent. • The hydrogel were facilely prepared by double-barrel injector gun to act as tissue adhesive. • H 2 O 2 -Vc was effective initiator for hydrogel and worked as disinfector for infected wound. • The hydrogel accelerated wound healing. 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. [ABSTRACT FROM AUTHOR]

• Thermo-/pH-sensitive hydroxypropyl chitin/tannic acid/ferric ion hydrogel developed. • The composite hydrogel can be easily injected to cover irregular wounds. • The hydrogel has good biocompatibility and prolonged antibacterial activity. • The antibacterial composite hydrogel could accelerate wound healing without scars. Polysaccharide hydrogels have been widely used as wound dressings because of their biocompatibility and ability to provide moist environment for wound healing. However, bacterial infection often delays the healing process. Herein, a novel thermosensitive and pH-sensitive hydroxypropyl chitin/tannic acid/ferric ion (HPCH/TA/Fe) composite hydrogel was fabricated by a simple assembly. The pre-cooled hydrogel precursor solution can be injected onto the irregular wound area and gel rapidly at physiological temperature. The TA not only acted as a crosslinker to enhance mechanical properties of the hydrogel, but also as an antibacterial agent which could be sustainably released in response to the acidic environment. The composite hydrogel showed excellent broad-spectrum antibacterial activity up to 7 days with negligible cytotoxicity. Moreover, the hydrogel can inhibit bacterial infection and accelerate the wound healing process without scars in the mouse experiment. These results indicate the potential application of this composite hydrogel for the infected wound healing. [ABSTRACT FROM AUTHOR]

• A thermosensitive injectable hydrogels developed as a promising cell delivery vehicle for cardiac cell therapy. • Encapsulation of UCMSCs with CS/1.0 DEX/β-GP hydrogel can improve cell viability. • The delivery of HUVECs from CS/1.0 DEX/β-GP hydrogel showed a linear-like profile. • The prepared hydrogels could modulate the expression level of cTnI and Cx43 receptor of cardiac markers. • A thermosensitive injectable hydrogels developed as a promising cell delivery vehicle for cardiac cell therapy. • Encapsulation of UCMSCs with CS/1.0 DEX/β-GP hydrogel can improve cell viability. • The delivery of HUVECs from CS/1.0 DEX/β-GP hydrogel showed a linear-like profile. • The prepared hydrogels could modulate the expression level of cTnI and Cx43 receptor of cardiac markers. Acute myocardial infarction (MI) is a common cardiovascular disease with high mortality. In this study, an injectable thermosensitive hydrogel of chitosan (CS)/dextran (DEX)/β–glycerophosphate (β-GP) loaded with umbilical cord mesenchymal stem cells (UCMSCs) was prepared for MI treatment. The good biocompatibility of hydrogels was confirmed by 3T3 cells and HUVECs culture study in vitro. HUVECs encapsulated in the hydrogels showed a cell delivery ability. Furthermore, the results indicated that hydrogel could encapsulate most of UCMSCs and the cells exhibited good viability in CS/ 1.0DEX/β-GP hydrogels. The expression of cardiac markers of cTnI and Cx43 and signaling pathways of p-Akt and p-ERK1/2 were studied, and it showed that UCMSCs differentiate towards myocardium and has a great potential for therapeutic use of cardiac repair. In conclusion, the thermosensitive hydrogel of CS/1.0 DEX/β-GP loaded UCMSCs was a promising candidate as cell delivery vehicle for cardiac repair to reconstitute damaged myocardium. [ABSTRACT FROM AUTHOR]

• Cellulose-based and pH-sensitive injectable hydrogel composite was successfully constructed. • The injectable hydrogel system can realize pH-triggered slow drug release. • The degradation and mechanical property of hydrogels can be well tuned. Cellulose-based biocompatible, tunable and injectable hydrogels embedded with pH-responsive diblock copolymer micelles were constructed to achieve localized drug delivery with prolonged, stimuli-driven and slow-release function. First, we prepared two types of modified carboxymethyl cellulose (CMC) including hydrazide-modified carboxymethyl cellulose (CMC-NH 2) and oxidized carboxymethyl cellulose (CMC−CHO) with varying degrees of oxidation. Then, pH-responsive poly (ethylene oxide)-block-poly (2-(diisopropylamino) ethyl methacrylate) (PEO-b-PDPA) copolymers as micelle cores to carry hydrophobic substances were also synthesized through atom transfer radical polymerization (ATRP). An injectable hydrogel composite system was finally obtained by mixing CMC-NH 2 and CMC−CHO polymer suspensions containing PEO-b-PDPA copolymer micelles through a Schiff base reaction. This newly-synthesized, tunable, cellulose-based double barrier system exhibits a pH-triggered, prolonged, and slow-release profile based on the release test using both Nile Red dye and doxorubicin. The hydrogel system also exhibited comparable storage moduli and tunable degradation properties. [ABSTRACT FROM AUTHOR]