Injectable Self-healing Hydrogels Research Articles

PH-Responsive injectable self-healing hydrogels loading Au nanoparticles-decorated bimetallic organic frameworks for synergistic sonodynamic-chemodynamic-starvation-chemo therapy of cancer

A novel and efficient cancer therapy was developed using a smart hydrogel containing multifunctional bimetallic organic frameworks and anticancer drugs. The injectable self-healing hydrogel with pH-responsiveness was constructed through borate ester and imine bonds among dopamine-grafted sodium alginate (SADA), hydroxypropyl chitosan (HPCS) and 2-formylphenylboronic acid (2-FPBA). The Au nanoparticles-decorated Ti/Fe bimetallic organic framework tetragonal nanosheets (Au/TF-MOF TNS) were synthesized and incorporated into the hydrogel with the anticancer drugs doxorubicin (DOX). Upon intratumoral injection of nanocomposite hydrogel, the acidic tumor microenvironment triggered the cleavage of borate ester and imine bonds, causing the hydrogel to break down and accelerating the release of both Au/TF-MOF TNS and DOX. These Au/TF-MOF TNS functioned as nanozymes, producing hydroxyl radicals (·OH) for chemodynamic therapy (CDT), generating oxygen (O2) to support sonodynamic therapy (SDT), and depleting glucose for starvation therapy (ST). Additionally, the Au/TF-MOF TNS served as sonosensitizers, capable of converting O2 into singlet oxygen (1O2) upon ultrasound irradiation to achieve SDT. Therefore, this nanocomposite hydrogel system enabled synergistic sonodynamic-chemodynamic-starvation-chemo therapy (SDT-CDT-ST-CT) of cancer, presenting a promising platform for advanced cancer therapy strategies.

Biodegradable chitin nanofiber-alginate dialdehyde hydrogel: An injectable, self-healing scaffold for anti-tumor drug delivery

Injectable hydrogels fabricated from natural polymers have attracted increasing attentions for their potential in biomedical application owing to the biocompatibility and biodegradability. A new class of natural polymer based self-healing hydrogel is constructed through dynamic covalent bonds. The injectable self-healing hydrogels are fabricated by introducing alginate aldehyde to form Schiff base bonds with the chitin nanofibers. These hydrogels demonstrate excellent self-healing properties, injectability, and pH-responsive sol-gel transition behaviors. As a result, they can serve as carriers to allow an effective encapsulation of doxorubicin (DOX) for drug delivery. Furthermore, these hydrogels exhibit excellent biocompatibility and degradability in vitro and in vivo. The sustained release of DOX from the hydrogels effectively suppresses tumor growth in animal models without causing significant systemic toxicity, suggesting their potential application in anti-tumor therapies.

Injectable, self-healing hyaluronic acid-based hydrogels for spinal cord injury repair

The cystic cavity that develops following spinal cord injury is a major obstacle for repairing spinal cord injury (SCI). The injectable self-healing biomaterials treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury. Herein, a natural extracellular matrix (ECM) biopolymer hyaluronic acid-based hydrogel was developed based on multiple dynamic covalent bonds. The hydrogels exhibited excellent injectable and self-healing properties, could be effectively injected into the injury site, and filled the lesion cavity to accelerate the tissue repair of traumatic SCI. Moreover, the hydrogels were compatible with cells and various tissues and possessed proper stiffness matched with nervous tissue. Additionally, when implanted into the injured spinal cord site, the hyaluronic acid-based hydrogel promoted axonal regeneration and functional recovery by accelerating remyelination, axon regeneration, and angiogenesis. Overall, the injectable self-healing hyaluronic acid-based hydrogels are ideal biomaterials for treating traumatic SCI.

Gelatin/O-carboxymethyl chitosan injectable self-healing hydrogels for ibuprofen and naproxen dual release

Recently, a significantly greater clinical benefit has been reported with a combination of glucosamine sulfate and nonsteroidal anti-inflammatory drugs (NSAIDs) compared to either treatment alone for the growing osteoarthritis (OA) disease. So, this study introduces hydrogels using O-carboxymethyl chitosan (O-CMC, structurally akin glucosamine glycan), and Gelatin type A (GA) in a 1:2 ratio with β-glycerophosphate (βGPh) at varying percentages (5 %, 12.5 %, and 15 %). We show that hydrogel properties, adaptable for drug delivery or tissue engineering, can be fine-tuned based on OCMC:βGPh ratio. CMC/GA/βGPh-12.5 exhibited a swelling rate of 189 %, compressive stress of 164 kPa, and compressive modulus of 3.4 kPa. The self-healing hydrogel also exhibited excellent injectability through a 21-gauge needle, requiring only 5 N of force. Ibuprofen and Naproxen release from CMC/GA/βGPh-12.5 and CMC/GA/βGPh-15 of designed dimensions (bi-layer structures of different diameter and height) were measured, and drug release kinetics were estimated using mathematical equations (MATLAB and polyfit program).CMC/GA/βGPh-12.5 demonstrated significant antibacterial effects against E. coli and S. aureus, a high cell survival rate of 89 % against L929 fibroblasts, and strong cell adhesion, all indicating biocompatibility.These findings underscore potential of these hydrogels as promising candidates for treating inflammatory diseases such as osteoarthritis.

Doping proanthocyanidins into gel/zirconium hybrid hydrogel to reshape the microenvironment of diabetic wounds for healing acceleration

Infection and chronic inflammation caused by oxidative stress are major challenges in chronic wound healing. Preparing a simple, efficient hydrogel with reactive oxygen–scavenging properties for chronic wound repair is a promising strategy. Herein, we report an injectable, self-repairing hydrogel with antioxidant and antibacterial properties that can be used to regenerate diabetic wounds. Hydrogels are prepared by coordination crosslinking of gelatin (Gel), a natural biopolymer derived from collagen, with Zr4+. Because of the dynamic properties of metal ion coordination bonds and the bactericidal effect of Zr4+, the obtained coordination hydrogels exhibit self-healing, injectable, and antibacterial properties. The plant polyphenol “proanthocyanidins,” which has reactive oxygen–scavenging and anti-inflammatory effects, was simultaneously loaded into the coordination hydrogel during cross-linking. We obtained a versatile hydrogel that is easy to prepare, resistant to mechanical irritation, and antioxidant, and antibacterial in vitro. We further demonstrated that the injectable self-healing hydrogels could effectively repair diabetic skin wounds and accelerate collagen deposition and wound healing. This study shows that the multifunctional antioxidant hydrogel has great potential in developing multifunctional biomaterials for chronic wound healing.

Rapid self-healing carboxymethyl chitosan/hyaluronic acid hydrogels with injectable ability for drug delivery

In this study, the quaternized carboxymethyl chitosan (QCMCS), oxidized hyaluronic acid (OHA), 3,3′-dithiobis-(propionohydrazide) (DTP) were used as raw materials for the synthesis of hydrogels with excellent properties as carriers for drug release. The hydrogels were prepared by a simple “one-pot” method without external stimuli on the basis of interactions between formed dynamic covalent bonds (imine bonds, acylhydrazone bonds, disulfide bonds) and hydrogen bonds. The hydrogels had rapid self-healing properties, with a self-healing rate of 96 % after 30 min, as well as good pH responsiveness and excellent cytocompatibility (up to 98 % cell survival). The compressive stress of the hydrogels reached 423 kPa. Moreover, a representative drug (acetylsalicylic acid) demonstrated sustained release in the hydrogels (>72 h). The drug release behaviour was shown to be consistent with the Fick diffusion mechanism by kinetic modelling. Collectively, the findings demonstrate that the QCMCS + OHA + DTP injectable self-healing hydrogels are a potential material for the construction of pH-controlled drug delivery platforms.

An injectable, self-healing, and antioxidant collagen- and hyaluronic acid-based hydrogel mediated with gallic acid and dopamine for wound repair

Injectable self-healing hydrogels with antioxidation are required in wound dressings. Because oxidative damage caused by excessive reactive oxygen species (ROS) is a common issue associated with chronic non-healing wounds. Here, collagen (COL) - and hyaluronic acid (HA)-based hydrogel with antioxidant and injectable self-healing mediated with gallic acid (GA) and dopamine (DA) offers unique advantages for wound repair. The hydrogel is constructed by COL-grafted GA (CG), HA-grafted DA (HD) and γ-poly(glutamic acid) (γ–PGA) coupled with 3-aminophenylboric acid (APBA) via the dynamic boronic ester bonds. Rheological measurements and direct visual observation demonstrated the hydrogel's desirable injectability and self-healing properties. Additionally, the hydrogel exhibits tissue adhesion properties. Biocompatibility and cell migration tests showed that the hydrogel promotes cell proliferation and migration. In vitro, antioxidant and intracellular free radical scavenging assays confirmed the hydrogel's antioxidant property and ability to scavenge excess ROS. In vivo wound healing studies have demonstrated that hydrogel can promote angiogenesis, inhibit inflammation, and promote collagen fiber deposition to accelerate wound healing.

Adhesive injectable cellulose-based hydrogels with rapid self-healing and sustained drug release capability for promoting wound healing

Injectable biocompatible hydrogels with multiple functions, including self-healing, adhesion, antibacterial activity, and suitable mechanical properties, are highly desirable for enhancing wound healing. In this study, a new class of multi-functional injectable self-healing cellulose-based hydrogels was synthesised using dynamic covalent acylhydrazone linkages for wound dressing. The carboxymethyl cellulose-graft-adipic dihydrazide (CMC-ADH)/4-Formylbenzoic acid-terminated poly(ethylene glycol) (PEG-FBA) (CMC-ADH/PEG-FBA) hydrogels have adjustable gelation time and excellent self-healing ability. In addition, drug release and in vitro antibacterial activities against Gram-positive and Gram-negative bacteria confirmed the sustained drug-release capacity of the hydrogels. Moreover, haemostasis and wound-healing effects were investigated using an in vivo haemorrhaging liver mouse model and a full-thickness skin defect model, and the results indicated that they not only promoted the wound-healing process but also presented excellent haemostatic effects. The CMC-ADH/PEG-FBA gels also exhibited good adhesion to irregular wounds and significantly enhanced angiogenic ability in vivo. This excellent wound-healing performance occurs because hydrogels can quickly stop bleeding, provide a moist and closed environment for the wound to prevent bacterial invasion, release ciprofloxacin (CIP), reduce inflammatory reactions, and promote wound tissue regeneration. In summary, the synthesised multi-functional gels are ideal candidates for treating haemorrhages and irregular wounds.

Building a Poly(amino acid)/Chitosan-Based Self-Healing Hydrogel via Host-Guest Interaction for Cartilage Regeneration.

Cartilage injury is a very common joint disease, and cartilage repair is a great challenge in clinical treatment due to the specific structure of cartilage tissue and its microenvironment in vivo. The injectable self-healing hydrogel is a very promising candidate as a cartilage repair material because of its special network structure, high water retention and self-healing properties. In this work, a self-healing hydrogel cross-linked by host-guest interaction between cyclodextrin and cholic acid was developed. The host material was composed of β-cyclodextrin and 2-hydroxyethyl methacrylate-modified poly(l-glutamic acid) (P(LGA-co-GM-co-GC)), while the guest material was chitosan modified by cholic acid, glycidyl methacrylate, and (2,3-epoxypropyl)trimethylammonium chloride (EPTAC) (QCSG-CA). The host-guest interaction self-healing hydrogels, named as HG hydrogels (HG gel), exhibited excellent injectability and self-healable property, and the self-healing efficiency was greater than 90%. Furthermore, in order to enhance the mechanical properties and slow down the degradation of the HG gel in vivo, the second network was constructed by photo-cross-linking in situ. Biocompatibility tests showed that the enhanced multi-interaction hydrogel (MI gel) was extremely suitable for cartilage tissue engineering both in vitro and in vivo. In addition, the adipose derived stem cells (ASCs) in MI gel were able to differentiate cartilage effectively in vitro in the presence of inducing agents. Subsequently, the MI gel without ASCs was transplanted into rat cartilage defects in vivo for the regeneration of cartilage. After 3 months postimplantation, new cartilage tissue was successfully regenerated in a rat cartilage defect. All results indicated that the injectable self-healing host-guest hydrogels have important potential applications in cartilage injury repair.

Physicochemical and in vitro biological evaluation of an injectable self-healing quaternized chitosan/oxidized pectin hydrogel for potential use as a wound dressing material

Injectable self-healing hydrogels are attractive materials for use as wound dressings. To prepare such hydrogels, the current study used quaternized chitosan (QCS) to improve the solubility and antibacterial activity and oxidized pectin (OPEC) to introduce aldehyde groups for Schiff's base reaction with the amine groups from QCS. Self-healing hydrogels were made by co-injection of polymer solutions at specific polymer concentrations and reagent ratios that optimized both Schiff's base reactions and ionic interactions. The optimal hydrogel displayed self-healing 30 min after cutting and continuous self-healing during continuous step strain analysis, rapid gelation (< 1 min), a storage modulus of 394 Pa, and hardness of 700 mN, and compressibility of 162 mN s. The adhesiveness of this hydrogel (133 Pa) was within a suitable range for application as a wound dressing. The extraction media from the hydrogel displayed no cytotoxicity to NCTC clone 929 cells and higher cell migration than the control. While the extraction media from the hydrogel was found not to have antibacterial properties, QCS was verified as having MIC50 of 0.04 mg/mL against both E. coli and S. aureus. Therefore, this injectable self-healing QCS/OPEC hydrogel has the potential use as a biocompatible hydrogel material for wound management.

Papillary fibroblast-recruiting injectable self-healing multifunctional hydrogels for wound regeneration

Papillary fibroblast-recruiting injectable self-healing multifunctional hydrogels for wound regeneration

One-pot synthesis of injectable self-healing thermoresponsive halloysite nanotube-reinforced nanocomposite hydrogels for tissue engineering

Injectable hydrogels that can fill irregular defects through a minimally invasive approach are of particular interest to replace invasive surgeries in tissue scaffold implantation. However, the use of injectable hydrogels is often restricted by the drawback of having poor mechanical properties. In this work, a novel halloysite nanotube (Hal)-based hydrogel was developed using bacterial cellulose and gelatin, as well as acid-treated Hal to serve a dual purpose of providing structural support for tissue regeneration while offering possibilities for drug delivery at a local site. The fabricated hydrogels were then analyzed physically and morphologically for injectability, gelling ability, self-healing capability, as well as composition characterization, surface morphology, mechanical performance, and biodegradability. Analyses revealed that all the hydrogels could be injected as a liquid, with an in-situ sol-gel transition occurring after 10 min at 37 °C. Furthermore, the honeycomb-like structure of the hydrogel and the rougher surface where Hal dispersed over the surfaces could also provide sufficient space and anchorage sites to facilitate cell attachment. With the moisture content reaching up to 85–92%, the hydrogels could provide a moist recovery environment for the healing process. More importantly, the incorporation of Hal greatly improved the compressive strength and Young's modulus up to 60% and 40%, respectively. Furthermore, antibiotic-loaded hydrogels demonstrated effective antimicrobial activity against Staphylococcus epidermidis, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-resistant S. aureus (MRSA). Collectively, such hydrogels with a minimally invasive delivery approach and the potential to aid in tissue regeneration can be applied in biomedical and tissue engineering applications, along with a combined local delivery of antimicrobial agents in the near future.

Thermoresponsive Self-Healing Zwitterionic Hydrogel as an In Situ Gelling Wound Dressing for Rapid Wound Healing.

It is highly desired yet challenging to fabricate biocompatible injectable self-healing hydrogels with anti-bacterial adhesion properties for complex wounds that can autonomously adapt to different shapes and depths and can promote angiogenesis and dermal collagen synthesis for rapid wound healing. Herein, an injectable zwitterionic hydrogel with excellent self-healing property, good cytocompatibility, and antibacterial adhesion was developed from a thermoresponsive ABA triblock copolymer poly[(N-isopropyl acrylamide)-co-(butyl acrylate)-co-(sulfobetaine methacrylate)]-b-poly(ethylene glycol)-b-poly[(N-isopropyl acrylamide)-co-(butyl acrylate)-co-(sulfobetaine methacrylate)] (PZOPZ). The prepared PZOPZ hydrogel exhibits a distinct thermal-induced sol-gel transition around physiological temperature and could be easily applied in a sol state and in situ gelled to adapt complex wounds of different shapes and depths for complete coverage. Meanwhile, the hydrogel possesses a rapid self-healing ability and can recover autonomously from damage to maintain structural and functional integrity. In addition, the CCK-8 and 2D/3D cell culture experiments revealed that the PZOPZ hydrogel dressing shows low cytotoxicity to L929 cells and can effectively prevent the adhesion of Staphylococcus aureus and Escherichia coli. In vivo investigations verified that the PZOPZ hydrogel could increase angiogenesis and dermal collagen synthesis and shorten the transition from the inflammatory to the proliferative stage, thereby providing more favorable conditions for faster wound healing. Overall, this work provides a promising strategy to develop injectable zwitterionic hydrogel dressings with multiple functions for clinic wound management.

Injectable protocatechuic acid based composite hydrogel with hemostatic and antioxidant properties for skin regeneration

Acute skin injuries require timely and effective treatment. Injectable self-healing hydrogels are a very promising approach, but they face many challenges because of the complex microenvironments of skin wound. Although hydrogels have been extensively studied for multifunction, injectable self-healing hydrogels with both hemostatic and antioxidant properties are rare. In this paper, gelatin grafted protocatechuic acid (GT-PCA) and oxidized-dextran (Odex) were used to engineer GT-PCA/Odex composite hydrogels via Schiff base reaction. The in vitro experimental results show that the hydrogels not only are injectable, self-healing, hemostatic, antioxidant, but also have good degradability, adhesion and biocompatibility. Further, the hydrogels can promote wound healing in full-thickness mouse skin defect models by reducing inflammation and increasing angiogenesis, collagen deposition and granulation tissue formation. Notably, the preparation method of GT-PCA/Odex hydrogels is gentle and simple, the hydrogel system has bright prospects in the treatment of acute skin injury and is expected to be applied in clinical trials.

Injectable hyaluronic acid/hydroxyapatite composite hydrogels as cell carriers for bone repair

The natural polysaccharide/hydroxyapatite hydrogels are of great interest to bone tissue engineering, but the interfacial mismatch between rigid hydroxyapatite and soft polysaccharide phase in these hydrogels remains unsolved, which is unfavorable to achieving uniform dispersion of hydroxyapatite particles in the hydrogel matrices. Herein, hyaluronic acid (Hya), an extracellular matrix constituent, was chosen as the template for biological mineralization to synthesize Hya/hydroxyapatite hybrid particles (HAHs). The oxidized Hya/hydroxyapatite hybrid particles (OHAHs) were obtained by oxidating the Hya in the HAHs. These OHAHs were the ball-flower particles hybridized with ca. 22 % oxidized Hya. Then, different concentrations of OHAHs were introduced to prepare hydroxyapatite composite hydrogels (HCH) via Schiff-base reaction of oxidized Hya and carboxymethyl chitosan. The injectability and self-healing of HCH were evaluated and the introduction of OHAHs significantly increased the storage modulus. The gelation time of HCH showed a negative relation with the concentration of OHAHs while the storage modulus presented a positive correlation. MTT assays and live/dead staining of L929 cells co-cultured with HCH confirmed that the hydrogels had excellent cytocompatibility, and supported the adhesion and proliferation of cells under the three-dimension culture conditions. These injectable self-healing hydrogels suitable for cell encapsulation were potentially useful for bone defect repair.

Injectable nanofiber-polysaccharide self-healing hydrogels for wound healing

Injectable self-healing hydrogels of natural polysaccharides that mimic the extracellular matrix to promote cellular growth are attractive materials for wound healing. Here, a novel hydrogel was fabricated based on carboxymethyl chitosan (CS) and aldehyde functionalized sodium alginate via Schiff base reaction. To enhance the hydrogel's properties, carboxymethyl-functionalized polymethyl methacrylate (PMAA) short nanofibers were obtained through sodium hydroxide-treated polymethyl methacrylate nanofibers, and added to a CS solution. Gelation time was determined for different hydrogels including 0–5 mg/mL PMAA short nanofibers. The nanofiber hydrogels were tested for their injectability and self-healing abilities and were demonstrated to be easily injectable with excellent self-healing abilities. Additionally, in vitro cytocompatibility experiments, good interaction between the cultured cells and hydrogels was seen. Further, the polysaccharide hydrogel containing short PMMA nanofibers significantly facilitated wound healing in rats compared with the polysaccharide hydrogel and control groups. Thus, the developed hydrogel has great potential for wound healing applications.

An injectable, self-healing, electroconductive extracellular matrix-based hydrogel for enhancing tissue repair after traumatic spinal cord injury

Injectable biomaterial-based treatment is a promising strategy to enhance tissue repair after traumatic spinal cord injury (SCI) by bridging cavity spaces. However, there are limited reports of injectable, electroconductive hydrogels with self-healing properties being employed for the treatment of traumatic SCI. Hence, a natural extracellular matrix (ECM) biopolymer (chondroitin sulphate and gelatin)-based hydrogel containing polypyrrole, which imparted electroconductive properties, is developed for traumatic SCI repair. The resulting hydrogels showed mechanical (~928 Pa) and conductive properties (4.49 mS/cm) similar to natural spinal cord tissues. Moreover, the hydrogels exhibited shear-thinning and self-healing abilities, which allows it to be effectively injected into the injury site and to fill the lesion cavity to accelerate the tissue repair of traumatic SCI. In vitro, electroconductive ECM hydrogels promoted neuronal differentiation, enhanced axon outgrowth, and inhibited astrocyte differentiation. The electroconductive ECM hydrogel activated endogenous neural stem cell neurogenesis in vivo (n = 6), and induced myelinated axon regeneration into the lesion site via activation of the PI3K/AKT and MEK/ERK pathways, thereby achieving significant locomotor function restoration in rats with spinal cord injury (p < 0.001, compared to SCI group). Overall, the injectable self-healing electroconductive ECM-based hydrogels developed in this study are ideal biomaterials for treatment of traumatic SCI.

Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg2+/curcumin from injectable self-healing hydrogels.

Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing.Methods: In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg2+ and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated in vitro and in vivo. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests.Results: The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg2+ promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing.Conclusions: The composite hydrogel mediated sustained in situ release of curcumin and Mg2+ to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.

Injectable Self-Healing Hydrogels Containing CuS Nanoparticles with Abilities of Hemostasis, Antibacterial activity, and Promoting Wound Healing.

Injectable self-healing hydrogels containing functional nanoparticles (NPs) have attracted much attention in many fields of biomedicine. A series of injectable self-healing hydrogels containing PEGylation CuS NPs based on N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OA) were developed by taking advantages of the unique functions of CuS NPs and chitosan, referred to as CuS NP hydrogels or CEC-OAm-CuSn, where "m" stands for the concentration percentage of the added OA solution (w/v) and "n" represents the molar concentration of CuS NPs in the hydrogels. The physical properties of CuS NP hydrogels, syringeability, rapid self-repair ability, and photothermal performance were systematically investigated. The multiple functions for CuS NP hydrogels requested in the skin healing process were explored. The results showed that CuS NP hydrogels had not only adjustable physical properties and good injectable self-healing characteristics but also excellent functionalities, concurrently including hemostatic ability, bacteria killing capability, and cell migration and proliferation promotion. In vivo wound healing and histomorphological examinations of immunofluorescence staining in a mouse full-thickness wound model demonstrated good acceleration effects of these hydrogels for infected wound healing. Therefore, these injectable self-healing CuS NP hydrogels which possess the abilities of hemostasis, antibacterial activity, and infected-wound healing promotion exhibit great potential as in situ wound dressings.

Injectable self-healing CuS nanoparticle complex hydrogels with antibacterial, anti-cancer, and wound healing properties

It is of significant importance to develop an injectable self-healing hydrogel system that can simultaneously deal with antibacterial treatment, tumor therapy and wound healing acceleration for biomedical fields. Herein, a system of CuS nanoparticle complex (CuS NC) hydrogels with multiple functions is firstly developed through incorporating polyethylene glycol (PEG)-functionalized CuS nanoparticles (CuS NPs) with surface amino groups into a 3D network of oxidized dextran (ODex) and PEG with amino end groups. The in situ formed CuS NC hydrogels display not only excellent self-healing and injectable abilities, but also good biocompatibility for biomedical application. The introduction of CuS NPs endows the hydrogels with outstanding photothermal/photodynamic performance under near-infrared laser irradiation, creating the capability to fully kill S.aureus and E.coli bacteria, and to inhibit tumor growth in a subcutaneous skin-tumor model. The CuS NC hydrogels maintain sustained release of Cu2+ and moist microenvironment, and thus effectively accelerate wound healing in vivo. This work illustrates a facile strategy to prepare injectable, multifunctional nanoparticle hybrid hydrogels which can be used severally or simultaneously for bacterial infection treating, skin wound healing and skin-tumor therapy.