Hyaluronic acid/chitin thermosensitive hydrogel loaded with TGF-ß1 promotes meniscus repair in rabbit meniscus full-thickness tear model.

Repair of the damaged meniscus is a scientific challenge owing to the poor self-healing potential of the white area of the meniscus. Tissue engineering provides a new method for the repair of meniscus injuries. In this study, we explored the superiority of 2% hyaluronic acid chitin hydrogel in temperature sensitivity, in vitro degradation, biocompatibility, cell adhesion, and other biological characteristics, and investigated the advantages of hyaluronic acid (HA) and Transforming Growth Factor ß1 (TGF-ß1) in promoting cell proliferation and a matrix formation phenotype. The hydrogel loaded with HA and TGF-ß1 promoted cell proliferation. The HA + TGF-ß1 mixed group showed the highest glycosaminoglycan (GAG) content and promoted cell migration. Hydroxypropyl chitin (HPCH), HA, and TGF-ß1 were combined to form a composite hydrogel with a concentration of 2% after physical cross-linking, and this was injected into a rabbit model of a meniscus full-thickness tear. After 12 weeks of implantation, the TGF-ß1 + HA/HPCH composite hydrogel was significantly better than HPCH, HA/HPCH, TGF-ß1 + HPCH, and the control group in promoting meniscus repair. In addition, the new meniscus tissue of the TGF-ß1 + HA/HPCH composite hydrogel had a tissue structure and biochemical content similar to that of the normal meniscus tissue.

Injectable Tannin-Containing Hydroxypropyl Chitin Hydrogel as Novel Bioactive Pulp Capping Material Accelerates Repair of Inflamed Dental Pulp.

Conventional pulp capping materials have limited anti-inflammatory capacity. It is necessary to develop more effective pulp capping material for the treatment of inflamed pulps. Tannic acid (TA) is a natural, water-soluble polyphenol with antimicrobial and anti-inflammatory properties. This study aimed to investigate the effects of a tannin-containing hydroxypropyl chitin hydrogel (HPCH/TA hydrogel) as an innovative pulp capping material. The physicochemical properties of the composite hydrogels were characterized. The effects of HPCH/TA hydrogel as a pulp capping material were evaluated in vitro and in vivo. The underlying mechanism of the anti-inflammatory effects of HPCH/TA hydrogel was explored. The HPCH/TA hydrogel demonstrated favorable temperature sensitivity, injectability, and antibacterial properties. In vitro, the HPCH/TA hydrogel effectively promoted the proliferation of human dental pulp cells and inhibited interleukin-1ß, interleukin-6, and tumor necrosis factor-α expression, possibly by suppressing the nuclear factor kappa-B pathway. In vivo, on the fourth day after capping, the HPCH/TA hydrogel group showed lower inflammatory scores compared to the control and iRoot BP Plus (commercial pulp capping material) group. By the sixth week, complete reparative dentin formation was observed in the HPCH/TA hydrogel group, with no difference in thickness compared to the iRoot BP Plus group. Collectively, the HPCH/TA hydrogel holds promise as a bioactive pulp capping material for promoting the repair of inflamed pulp in vital pulp therapy.

Lycium Barbarum Polysaccharide-Derived Nanoparticles Protect Visual Function by Inhibiting RGC Ferroptosis and Microglial Activation in Retinal Ischemia‒Reperfusion Mice.

Retinal ischemia‒reperfusion (IR) is a major contributor to vision impairment and irreversible vision loss due to retinal ganglion cell (RGC) injury or loss. Contemporary therapeutic approaches predominantly focus on the amelioration of symptoms rather than addressing the fundamental etiological factors. Oxidative stress is a notable feature and an important mediator of IR damage. Lycium barbarum polysaccharide (LBP), the main active ingredient of Lycium barbarum, has various pharmacological effects, including antioxidation, immunoregulation, and neuroprotective effects. In this study, the ROS-consumable moiety phenylboronic acid pinacol ester (PBA) is introduced to LBP molecules, which can self-assemble into nanoparticles in aqueous solution. This nanoparticle (termed PLBP) can reduce the cellular ROS levels and enhance the antioxidant capability of RGCs by activating the NRF2 pathway, thus protecting RGCs from ferroptosis and preserving visual function in response to IR injury. PLBP also reduces neuroinflammation by inhibiting the ability of microglia to phagocytose, migrate, secrete inflammatory cytokines, and activate the NF-κB pathway. In conclusion, this approach can be used as an inspiration for the future development of neuroprotective drugs.

Coprecipitation of Fe/Cr Hydroxides at Organic-Water Interfaces: Functional Group Richness and (De)protonation Control Amounts and Compositions of Coprecipitates.

Iron/chromium hydroxide coprecipitation controls the fate and transport of toxic chromium (Cr) in many natural and engineered systems. Organic coatings on soil and engineered surfaces are ubiquitous; however, mechanistic controls of these organic coatings over Fe/Cr hydroxide coprecipitation are poorly understood. Here, Fe/Cr hydroxide coprecipitation was conducted on model organic coatings of humic acid (HA), sodium alginate (SA), and bovine serum albumin (BSA). The organics bonded with SiO2 through ligand exchange with carboxyl (-COOH), and the adsorbed amounts and pKa values of -COOH controlled surface charges of coatings. The adsorbed organic films also had different complexation capacities with Fe/Cr ions and Fe/Cr hydroxide particles, resulting in significant differences in both the amount (on HA > SA(-COOH) ≫ BSA(-NH2)) and composition (Cr/Fe molar ratio: on BSA(-NH2) ≫ HA > SA(-COOH)) of heterogeneous precipitates. Negatively charged -COOH attracted more Fe ions and oligomers of hydrolyzed Fe/Cr species and subsequently promoted heterogeneous precipitation of Fe/Cr hydroxide nanoparticles. Organic coatings containing -NH2 were positively charged at acidic pH because of the high pKa value of the functional group, limiting cation adsorption and formation of coprecipitates. Meanwhile, the higher local pH near the -NH2 coatings promoted the formation of Cr(OH)3. This study advances fundamental understanding of heterogeneous Fe/Cr hydroxide coprecipitation on organics, which is essential for successful Cr remediation and removal in both natural and engineered settings, as well as the synthesis of Cr-doped iron (oxy)hydroxides for material applications.

Synthesis and characterization of thermosensitive 2-hydroxypropyl-trimethylammonium chitin and its antibacterial sponge for noncompressible hemostasis and tissue regeneration.

Noncompressible hemorrhage is a leading cause of preventable death in battlefield/civilian trauma. The development of novel injectable and biodegradable hemostatic sponges, with rapid shape recovery and excellent antibacterial activity that can control hemorrhage in noncompressible bleeding sites and promote in situ tissue regeneration is still urgently needed. In this study, thermo/pH sensitive 2-hydroxypropyl-trimethylammonium chitins (QCHs) with low degree of quaternization substitution (DS: 0.07-0.23) and high degree of acetylation (DA: 0.91-0.94) were synthesized homogeneously for the first time. Their chemical compositions including DS and DA were characterized accurately by proton NMR for the first time. High strength QCH based sponges with good water/blood absorbency, rapid shape recovery and good antibacterial activity were prepared without using any crosslinkers but only due to their thermosensitive property, since they are soluble at low temperature but insoluble at high temperature. Compared with commercial products, the QCH sponges with cationic groups had the stronger pro-coagulant ability, better hemostatic effect in normal/heparinized liver perforation and femoral artery models in rats and porcine subclavian arteriovenous resection model. Moreover, the porous structure and biodegradability of the QCH sponges could promote in situ tissue regeneration. Overall, the QCH sponges show great clinical translational potential for noncompressible hemorrhage and tissue regeneration.

Structure and properties of sulfopropyl chitins prepared in NaOH/urea aqueous solutions.

A series of sulfopropyl chitins (SCs) with the degree of substitution (DS) ranging from 0.11 to 0.40 and high degree of acetylation (DA ≥ 0.82) were homogeneously synthesized by reacting chitin with sodium 3-chloro-2-hydroxypropanesulfonate (SCHPS) in NaOH/urea aqueous solutions under mild conditions. The structure and properties of SCs were characterized with 1H NMR, CP/MAS 13C NMR, FT-IR, XPS, XRD, elemental analysis, GPC, AFM, ζ-potential and rheological measurements. The mild reaction conditions resulted in less N-deacetylation and uniform structures with substitution occurring predominantly at the hydroxyl groups at C6 of the chitin backbone. The DS value for SC soluble in dilute alkali solution is as low as 0.16. SC exhibited good solubility in distilled water when its DS value reached 0.28. Water-soluble SCs self-assembled in water into micelles by the attractive hydrophobic and hydrogen-bonding interactions between polymer chains. The water-insoluble SC-2 with lower DS could thermally form smart hydrogels at body temperature (37 °C) in physiological condition. Moreover, the SCs exhibited good biocompatibility, making them suitable for biomedical applications.

Water soluble AIEgen-based thermosensitive and antibacterial hydroxypropyl chitin hydrogels for non-invasive visualization and wound healing.

Antimicrobial hydrogels containing antibacterial agents have been extensively studied for postoperative infections, wound repair and tissue engineering. However, the abuse of antibiotics has led to the enhancement of bacterial resistance and traditional antibacterial agents are losing their effect. Therefore, fabricating novel and efficient antibacterial hydrogels with enhanced photodynamic antimicrobial activity, good biocompatibility, biodegradability and injectability are highly desirable for clinical application. Herein, a fluorescent and sunlight-triggered synergetic antibacterial thermosensitive hydrogel (red fluorescent hydroxypropyl chitin, redFHPCH) is constructed based on a new water-soluble AIEgen (aggregation-induced emission fluorogen) covalently introduced in hydroxypropyl chitin for non-invasive visualization and wound healing. The thermosensitive redFHPCH solution showing good injectability with fluidity at low temperature was completely transformed into hydrogel under body temperature. The in vitro and in vivo visualization and reactive oxygen species (ROS) generation of the redFHPCH hydrogel are demonstrated clearly because of its excellent AIE fluorescence imaging quality in the red/near-infrared region and superefficient ROS production by sunlight. Moreover, the redFHPCH hydrogel with positively charged quaternary ammonium groups displays a strong synergistic antibacterial effect for healing of infected wound under sunlight irradiation. We believe that this novel strategy can open a new door to explore diversified and multifunctional hydrogels for clinical application.

Immunogenicity and protective effects of recombinant bivalent COVID-19 vaccine in mice and rhesus macaques.

Coronavirus disease (COVID-19) is still spreading rapidly worldwide, and a safe, effective, and cheap vaccine is still required to combat the COVID-19 pandemic. Here, we report a recombinant bivalent COVID-19 vaccine containing the RBD proteins of the prototype strain and beta variant. Immunization studies in mice demonstrated that this bivalent vaccine had far greater immunogenicity than the ZF2001, a marketed monovalent recombinant protein COVID-19 vaccine, and exhibited good immunization effects against the original COVID-19 strain and various variants. Rhesus macaque challenge experiments showed that this bivalent vaccine drastically decreased the lung viral load and reduced lung lesions in SARS-CoV-2 (the causative virus of COVID-19)-infected rhesus macaques. In summary, this bivalent vaccine showed immunogenicity and protective efficacy that was far superior to the monovalent recombinant protein vaccine against the prototype strain and provided an important basis for developing broad-spectrum COVID-19 vaccines.

Electron beam irradiation modified carboxymethyl chitin microsphere-based hemostatic materials with strong blood cell adsorption for hemorrhage control.

Timely control of coagulopathy bleeding can effectively reduce the probability of wound infection and mortality. However, it is still a challenge for microsphere hemostatic agents to achieve timely control of coagulopathy bleeding. In this work, the CCM-g-AA@DA hemostatic agent based on carboxymethyl chitin microspheres, CCM, was synthesized using electron beam irradiation-induced grafting polymerization of acrylic acid and coupling with dopamine. Irradiation grafting endowed the microspheres with excellent adsorption performance and a rough surface. The microspheres showed a strong affinity to blood cells, especially red blood cells. The maximum adsorption of red blood cells is up to approximately 100 times that of the original microspheres, the CCM. The introduction of dopamine increased the tissue adhesion of the microspheres. At the same time, the microspheres still possessed good blood compatibility and biodegradability. Furthermore, the CCM-g-AA@DA with Fe3+ achieved powerful procoagulant effects in the rat anticoagulant bleeding model. The bleeding time and blood loss were both reduced by about 90% compared with the blank group, which was superior to that of the commercially available collagen hemostatic agent Avitene™. In summary, the CCM-g-AA@DA hemostatic agent shows promising potential for bleeding control in individuals with coagulation disorders.

Hemostasis-osteogenesis integrated Janus carboxymethyl chitin/hydroxyapatite porous membrane for bone defect repair.

Barrier membranes with osteogenesis are desirable for promoting bone repair. Janus membrane, which has a bilayered structure with different properties on each side, could meet the osteogenesis/barrier dual functions of guided bone regeneration. In this work, new biodegradable Janus carboxymethyl chitin membrane with asymmetric pore structure was prepared based on thermosensitive carboxymethyl chitin without using any crosslinkers. Nano-hydroxyapatites were cast on single-sided membrane. The obtained carboxymethyl chitin/nano-hydroxyapatite Janus membrane showed dual biofunctions: the dense layer of the Janus membrane could act as a barrier to prevent connective tissue cells from invading the bone defects, while the porous layer (with pore size 100-200 µm) containing nano-hydroxyapatite could guide bone regeneration. After implanted on the rat critical-sized calvarial defect 8 weeks, carboxymethyl chitin/nano-hydroxyapatite membrane showed the most newly formed bone tissue with the highest bone volume/total volume ratio (10.03 ± 1.81 %, analyzed by micro CT), which was significantly better than the commercial collagen membrane GTR® (5.05 ± 0.76 %). Meanwhile, this Janus membrane possessed good hemostatic ability. These results suggest a facile strategy to construct hemostasis-osteogenesis integrated Janus carboxymethyl chitin/hydroxyapatite membrane for guided bone regeneration.

Biodegradable photothermal thermosensitive hydrogels treat osteosarcoma by reprogramming macrophages.

Osteosarcoma is one of the most common malignant tumors in children and tends to occur around the knee. Problems such as recurrence and metastasis are the outcomes of traditional treatment methods. One of the reasons for these issues is the infiltration of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Photothermal immunotherapy has emerged as one of the most potent approaches for cancer treatment. In this study, we designed a biodegradable, injectable, and photothermal hydrogel that functions to reprogram TAMs into classically activated macrophages (M1) based on hydroxypropyl chitin (HPCH), tannic acid and ferric ions (HTA). We found that HTA had better photothermal efficiency than a pure hydrogel; its photothermal repeatability is good and it can be NIR (808 nm) irradiated as needed. In addition, the precooled hydrogel solution can be injected into the tumor and it can rapidly gel in situ. In vitro, HTA with NIR irradiation (HTA + NIR) induced the apoptosis of K7M2 cancer cells. In vivo, the local administration of HTA + NIR exerted photothermal killing of primary tumors and reprogramming of TAMs into M1-type macrophages in the TME. Therefore, the injectable photothermally active antitumor hydrogel has great potential for modulating the TME to treat bone tumors.

Thermosensitive hydrogel for cartilage regeneration via synergistic delivery of SDF-1α like polypeptides and kartogenin.

Regeneration of injured articular cartilage is limited by low early-stage recruitment of stem cells and insufficient chondrogenic differentiation. Hydrogels are widely used to repair cartilage because they have excellent mechanical and biological properties. In this study, a dual drug-loaded thermosensitive hydroxypropyl chitin hydrogel (HPCH) system was prepared to release stromal-derived factor-1α-like polypeptides (SDFP) and kartogenin (KGN) for stem-cell recruitment and chondrogenic differentiation. The hydrogel had a network structure that promoted cell growth and nutrient exchange. Moreover, it was temperature sensitive and suitable for filling irregular defects. The system showed good biocompatibility in vitro and promoted stem-cell recruitment and chondrogenic differentiation. Furthermore, it reduced chondrocyte catabolism under inflammatory conditions. Animal experiments demonstrated that the dual-drug hydrogel systems can promote the regeneration of articular cartilage in rats. This study confirmed that an HPCH system loaded with KGN and SDFP could effectively repair articular cartilage defects and represents a viable treatment strategy.

Silver loaded biodegradable carboxymethyl chitin films with long-lasting antibacterial activity for infected wound healing.

Bacteria-related infections are one of the main causes of human skin infections, which are associated with the delay of wound healing and secondary complications. In this work, a series of novel biodegradable films based on thermosensitive carboxymethyl chitin were prepared without using any crosslinkers. All the carboxymethyl chitin films had good flexibility, high transparency, and appropriate water absorption capacity, and could provide a moist environment for wound healing. The silver ions (Ag+) were incorporated on the LTCF-5 film, which had the best mechanical strength (56.39 MPa in the dry state and 0.66 MPa in the wet state) among the carboxymethyl chitin films and was higher than those of the reported biodegradable dressings and commercially available dressings. Compared with the commercial hydrofiber dressing with silver (AQUACEL®), the composite film could provide slow and sustained release of Ag+ with good strength and biodegradability, and displayed excellent long-lasting antibacterial activity in vitro against both S. aureus and E. coli without obvious cytotoxicity, which still possessed good antibacterial activity with almost 100% bacteriostatic rates after soaking in phosphate buffered saline for 7 days. More importantly, the Ag+ loaded carboxymethyl chitin film could promote infected cutaneous wound healing in a S. aureus infected full-thickness cutaneous defect in vivo model because of its long-lasting antibacterial activity, good biocompatibility, exudate absorption and ability to maintain a moist environment. Thus Ag+ loaded carboxymethyl chitin films are excellent candidates for infected wound healing.

Visualization of degradation of injectable thermosensitive hydroxypropyl chitin modified by aggregation-induced emission.

The reversible thermosensitive hydroxypropyl chitin (HPCH) has been widely investigated for drug delivery, tissue engineering, wound repair and antibacterial hemostasis. To achieve non-invasive and real-time visualization of in vivo degradation of HPCH, aggregation-induced emission fluorogen (AIEgen) was introduced covalently in HPCH in water to obtain thermosensitive fluorescent hydroxypropyl chitin (FHPCH) avoiding using any organic solvent. The obtained fluorescent FHPCH hydrogel showed strong yellow-green fluorescence feature under UV irradiation, enabling visualization of the hydrogel with reversible thermosensitivity and reliable injectability. The in vitro enzymatic degradation study of FHPCH hydrogel showed that the attenuation of fluorescence intensity well matched with hydrogel weight loss. The injection through a 26-gauge needle for real-time fluorescence imaging in mice indeed indicated that AIE modified injectable thermosensitive FHPCH can be used for non-invasive, continuous and real-time visualization and quantitative analysis of in vivo degradation. This provides a new method for non-invasive real-time monitoring of similar implantable materials.

Injectable immunomodulation-based porous chitosan microspheres/HPCH hydrogel composites as a controlled drug delivery system for osteochondral regeneration.

The inappropriate regenerated fibrous cartilage and subchondral bone of the injured chondral defect ultimately cause degeneration of the regenerated cartilage, which eventually leads to the failure of cartilage repair. In this study, we developed a macrophage-modulated and injectable 'building block' drug delivery system comprised of porous chitosan (CS) microspheres and hydroxypropyl chitin (HPCH) hydrogel, where the dimethyloxallyl glycine (DMOG) was encapsulated in the thermosensitive HPCH hydrogel (HD) while kartogenin (KGN) was conjugated on the porous CS microspheres (CSK-PMS). The developed HD/CSK-PMS composite scaffold effectively modulated the microenvironment at the defect site, achieved local macrophage M2 polarization and promoted cartilage regeneration. The fast-degradable HD favored hyaline cartilage regeneration, while the highly stable CSK-PMS supported the endochondral ossification and regenerated the subchondral bone. In vitro and in vivo evaluations revealed that the newly developed HD/CSK-PMS as a controlled drug delivery system could effectively create M2 macrophage microenvironment and orchestrate osteochondral (OC) regeneration. These findings indicate the importance of the immune microenvironment and subchondral bone for high-quality cartilage repair, and thus the immunomodulation-based hydrogel/PMS composite system could be a promising candidate for OC regeneration.

Biodegradable carboxymethyl chitin-based hemostatic sponges with high strength and shape memory for non-compressible hemorrhage.

Uncontrolled hemorrhage of deep, narrow and non-compressible perforating wounds is responsible for many trauma deaths. In this work, a novel biodegradable hemostatic sponge based on thermosensitive carboxymethyl chitin was prepared via simple cryo-regeneration process without using any crosslinkers. The collagen and polydopamine were added to further enhance mechanical and hemostatic properties of the sponge. All the carboxymethyl chitin based sponges showed high strength with excellent water/blood-triggered shape memory property, and the highest compressive fracture wet-strength could reach about 291.2 kPa, which was almost higher than those of many reported biodegradable hemostatic sponges pre-swelled in water. More importantly, the carboxymethyl chitin-collagen-polydopamine sponges displayed much better blood-clotting capacity and superior hemostasis performance than gauze and clinically used collagen sponge iRegene@ in vitro and in the rat liver perforating wound model. This study revealed a facile strategy to construct the effective carboxymethyl chitin based hemostatic sponges for the deep and non-compressible perforating wound.

Size-tunable and biodegradable thrombin-functionalized carboxymethyl chitin microspheres for endovascular embolization.

As a minimally invasive method, endovascular embolization has been an effective strategy for controlling bleeding and tumor treatment. Herein, carboxymethyl chitin embolic microspheres were prepared with the aqueous two-phase carboxymethyl chitin/polyethylene glycol system without using any crosslinking agents and thrombin-functionalized embolic microsphere named as Thr@CMCHm-30 was made after covalent introduction of thrombin. The size of the microspheres can be adjusted from 5 to 500 µm. The data of in vitro and in vivo tests indicated that these microspheres possessed good degradability and biocompatibility. Meanwhile, Thr@CMCHm-30 can significantly promote blood clotting and enhance the strength of the blood clots. More importantly, Thr@CMCHm-30 displayed better embolization effect than that of the commercial available Gelfoam Alicon® and polyvinyl alcohol-based embolic microspheres CalliSpheres® in rat femoral vein and rabbit ear artery embolization models. Therefore the size-tunable and biodegradable thrombin-functionalized carboxymethyl chitin microspheres Thr@CMCHm-30 possess great potential for effective hemostasis and endovascular embolization.

Ropivacaine-loaded, hydroxypropyl chitin thermo-sensitive hydrogel combined with hyaluronan: an injectable, sustained-release system for providing long-lasting local anesthesia in rats.

BACKGROUND AND OBJECTIVE: Ropivacaine hydrochloride is a commonly used local anesthetic in clinics. However, local injection or continuous infusion of ropivacaine has been associated with several disadvantages. Accordingly, it is important to develop a new controlled release system for local administration of ropivacaine to achieve a prolong anesthetic effect, improve efficacy, and minimize the side effects. METHODS: We developed injectable hydroxypropyl chitin thermo-sensitive hydrogel (HPCH) combined with hyaluronan (HA), which was used to synthesize a ropivacaine (R)-loaded controlled release system. We then conducted drug release test and cytotoxicity assay in vitro. Importantly, we examined the analgesic effects and biocompatibility of this system in vivo by injecting different concentrations of R-HPCH-HA (7.5, 15, 22.5 mg/mL), ropivacaine hydrochloride (RHCL, 7.5 mg/mL), or saline (all in 0.5 mL) near the sciatic nerve in rats. RESULTS: R-HPCH-HA induced concentration-dependent thermal-sensory blockade and motor blockade in vivo. In hot plate test, R-HPCH-HA (22.5 mg/mL) induced a significant longer thermal-sensory blockade (17.7±0.7 hours), as compared with RHCL (7.5 mg/mL, 5.7±0.8 hours, n=6/group, p<0.05). It also produced a more prolonged motor blockade (6.8±0.8 hours) than RHCL (3.5±0.8 hours, p<0.05). R-HPCH-HA caused less cytotoxicity than RHCL, as indicated by the higher cell viability in vitro (n=8/group). CONCLUSION: Our findings in a sciatic nerve block model demonstrated that the injectable, ropivacaine-loaded controlled release system effectively prolonged the local analgesic effect in rats without notable side effects.

Modified porous carboxymethyl chitin microspheres by an organic solvent-free process for rapid hemostasis.

Rapid and effective hemorrhage control is essential to reduce mortality following traumatic injuries. Herein we developed an organic solvent-free process to prepare carboxymethyl chitin microsphere (CMCHm) in an aqueous two-phase system through heating and freeze-drying. To further enhance the hemostatic performance of CMCHm, we loaded calcium ions and in-situ polymerized dopamine to get modified hemostatic microspheres CMCHm-Ca2+ and CMCHm-PDA, respectively. The size of these microspheres was mainly distributed between 50 µm and 150 µm, and the porous microstructure was observed by SEM. The data of in vitro degradation, cell cytotoxicity, and hemolysis test indicated good biocompatibility of these microspheres. Importantly, CMCHm-Ca2+ and CMCHm-PDA displayed better hemostatic performance compared with CMCHm and the positive controls Yunnan baiyao® and Quickclean®. Especially, the bleeding time was reduced to 59 s (CMCHm-Ca2+) and 45 s (CMCHm-PDA) in the femoral artery/vein cut model, respectively. All these demonstrate CMCHm-Ca2+ and CMCHm-PDA hold great potential for rapid hemostasis.

An injectable photothermally active antibacterial composite hydroxypropyl chitin hydrogel for promoting the wound healing process through photobiomodulation.

Prevention of bacterial infection, acceleration of wound closure and promotion of skin regeneration are crucial in the wound healing process. In this work, the photothermal activity of an injectable thermosensitive composite hydrogel based on hydroxypropyl chitin (HPCH), tannic acid (TA) and ferric ions (Fe3+) was studied. It was found that the photothermal efficiency was enhanced when the molar ratio of Fe3+/TA increased up to 20. The composite hydrogel possessed good cytocompatibility and hemocompatibility with a low dosage of the antibacterial agent TA. In vitro and in vivo antibacterial tests showed that the HPCH/TA/Fe hydrogel possessed an effective and rapid bactericidal effect with 10 minutes of near-infrared laser irradiation. Furthermore, the combination of a low-level laser therapy with the hydrogel is conducive to the acceleration of wound closure and promotion of skin tissue repair. Thus, the injectable photothermally active antibacterial composite hydrogel has great potential for the infected skin wound regeneration in clinical applications.