Injectable Self-healing Hydrogel Research Articles

A hyaluronic acid hydrogel as a mild photothermal antibacterial, antioxidant, and nitric oxide release platform for diabetic wound healing

Hyaluronic acid (HA)-based biopolymer hydrogels are promising therapeutic dressings for various wounds but still underperform in treating diabetic wounds. These wounds are extremely difficult to heal and undergo a prolonged and severe inflammatory process due to bacterial infection, overexpression of reactive oxygen species (ROS), and insufficient synthesis of NO. In this study, a dynamic crosslinked hyaluronic acid (HA) hydrogel dressing (Gel-HAB) loaded with allomelanin (AMNP)-N, N′-dis-sec-butyl-N, N′-dinitroso-1, 4-phenylenediamine (BNN6) nanoparticles (AMNP-BNN6) was developed for healing diabetic wounds. The dynamic acylhydrazone bond formed between hydrazide-modified HA (HA-ADH) and oxidized HA (OHA) makes the hydrogel injectable, self-healing, and biocompatible. The hydrogel, loaded with AMNP-BNN6 nanoparticles, exhibits promising ROS scavenging ability and on-demand release of nitric oxide (NO) under near-infrared (NIR) laser irradiation to achieve mild photothermal antibacterial therapy (PTAT) (∼ 48 °C). Notably, the Gel-HAB hydrogel effectively reduced the oxidative stress level, controlled infections, accelerated vascular regeneration, and promoted angiogenesis, thereby achieving rapid healing of diabetic wounds. The injectable self-healing nanocomposite hydrogel could serve as a mild photothermal-enhanced antibacterial, antioxidant, and nitric oxide release platform for the treatment of diabetic wounds.

Dynamic hydrogel–metal–organic framework system promotes bone regeneration in periodontitis through controlled drug delivery

Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment’s impact on immune responses. This study explores a novel approach utilizing Metal–Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid's antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel’s synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system's efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis.Graphical

An Immune-Regulating Polysaccharide Hybrid Hydrogel with Mild Photothermal Effect and Anti-Inflammatory for Accelerating Infected Wound Healing.

Bacterial infections and excessive inflammation present substantial challenges for clinical wound healing. Hydrogels with mild photothermal (PTT) effects have emerged as promising agents owing to their dual actions: positive effects on cells and negative effects on bacteria. Here, an injectable self-healing hydrogel of oxidized konjac glucomannan/arginine-modified chitosan (OKGM/CS-Arg, OC) integrated with protocatechualdehyde-@Fe (PF) nanoparticles capable of effectively absorbing near-infrared radiation is synthesized successfully. The OC/PF hydrogels exhibit excellent mechanical properties, biocompatibility, and antioxidant activity. Moreover, in synergy with PTT, OC/PF demonstrates potent antibacterial effects while concurrently stimulating cell migration and new blood vessel formation. In methicillin-resistant Staphylococcus aureus-infected full-thickness mouse wounds, the OC/PF hydrogel displays remarkable antibacterial and anti-inflammatory activities, and accelerates wound healing by regulating the wound immune microenvironment and promoting M2 macrophage polarization. Consequently, the OC/PF hydrogel represents a novel therapeutic approach for treating multidrug-resistant bacterial infections and offers a technologically advanced solution for managing infectious wounds in clinical settings.

AgNPs loaded adenine-modified chitosan composite POSS-PEG hybrid hydrogel with enhanced antibacterial and cell proliferation properties for promotion of infected wound healing

Wound healing is a dynamic and complex process, it's urgent to develop new wound dressings with excellent performance to promote wound healing at the different stages. Here, a novel composite hydrogel dressing composed by silver nanoparticles (AgNPs) impregnated adenine-modified chitosan (CS-A) and octafunctionalized polyhedral oligomeric silsesquioxane (POSS) of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) solution was presented to solve the problem of wound infection. Modification of chitosan with adenine, not only can improve the water solubility of chitosan, but also introduce bioactive substances to promote cell proliferation. CS-A and POSS-PEG-CHO were cross-linked by Schiff-base reaction to form the injectable self-healing hydrogel. On this basis, AgNPs were added into the hydrogel, which endows the hydrogel with better antibacterial activity. Moreover, this kind of hydrogel exhibits excellent cell proliferation properties. Studies demonstrated that the hydrogel can significantly accelerate the closure of infected wounds. The histological analysis and immunofluorescence staining demonstrated that the wounds treated with the composite hydrogel exhibited fewer inflammatory cells, more collagen deposition and angiogenesis, faster regeneration of epithelial tissue. Above all, adenine-modified chitosan composite hydrogel with AgNPs loaded was considered as a dressing material with great application potential for promoting the healing of infected wounds.

Injectable Hydrogel Delivery System with High Drug Loading for Prolonging Local Anesthesia.

Peripheral nerve block is performed for precise pain control and lesser side effects after surgery by reducing opioid consumption. Injectable hydrogel delivery systems with high biosafety and moisture content have good clinical application prospects for local anesthetic delivery. However, how to achieve high drug loading and long-term controlled release of water-soluble narcotic drugs remains a big challenge. In this study, heterogeneous microspheres and an injectable gel-matrix composite drug delivery system are designed in two steps. First, heterogeneous hydrogel microspheres loaded with ropivacaine (HMS-ROP) are prepared using a microfluidic chip and in situ alkalization. An injectable self-healing hydrogel matrix (Gel) is then prepared from modified carboxymethylcellulose (CMC-ADH) and oxidized hyaluronic acid (OHA). A local anesthetic delivery system, Gel/HMS-ROP/dexmedetomidine (DEX), with long-term retention and drug release in vivo is prepared by combining HMS-ROP and Gel/DEX. The drug loading of HMS-ROP reached 41.1%, with a drug release time of over 160h in vitro, and sensory and motor blockade times in vivo of 48 and 36h, respectively. In summary, the sequential release and synergistic analgesic effects of the two anesthetics are realized using core-shell microspheres, DEX, and an injectable gel, providing a promising strategy for long-acting postoperative pain management.

Preparation and antitumor study of intelligent injectable hydrogel: Carboxymethyl chitosan–aldehyde gum Arabic composite graphene oxide hydrogel

In this study, we used polyaldehyde gum Arabic (OGA) and carboxymethyl chitosan (CMCS) as a gel matrix to form an injectable self-healing hydrogel by Schiff-base bonding. Further, graphene oxide (GO) was loaded with doxorubicin (DOX) to the hydrogel, which resulted in a CMCS-OGA/GO@DOX hydrogel. We achieved a DOX drug loading capacity of 43.80 ± 1.13 %. Rheological studies showed that GO hydrogels have improved mechanical properties. The in vitro release profile showed pH responsiveness with 88.21 % DOX release at pH 5.5. Biocompatibility studies showed that the hydrogel composition had good cytocompatibility with L929 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed a cell survival rate of 93.88 % within 48 h. The DOX-loaded hydrogel exhibited higher cell mortality in breast cancer cells (4 T1), with an inhibition rate of 79.4 % at 48 h. Acridine orange/ethidium bromide staining experiments on 4 T1 cells showed that when loaded with the same DOX concentration, the hydrogel significantly reduced the toxic effects on normal cells, whereas it had significant cytotoxic effects on cancer cells. This result indicates that the prepared GO hydrogel drug delivery system can serve as a novel approach for localized breast cancer treatment.

Photothermal synergistic nitric oxide controlled release injectable self-healing adhesive hydrogel for biofilm eradication and wound healing.

The development of injectable self-healing adhesive hydrogel dressings with excellent bactericidal activity and wound healing ability is urgently in demand for combating biofilm infections. Herein, a multifunctional hydrogel (QP/QT-MB) with near-infrared (NIR) light-activated mild photothermal/gaseous antimicrobial activity was developed based on the dynamic reversible borate bonds and hydrogen bonds crosslinking between quaternization chitosan (QCS) derivatives alternatively containing phenylboronic acid and catechol-like moieties in conjunction with the in situ encapsulation of BNN6-loaded mesoporous polydopamine (MPDA@BNN6 NPs). Given the dynamic reversible cross-linking feature, the versatile hybrid hydrogel exhibited injectability, flexibility, and rapid self-healing ability. The numerous phenylboronic acid and catechol-like moieties on the QCS backbone confer the hydrogel with specific bacterial affinity, desirable tissue adhesion, and antioxidant stress ability that enhance bactericidal activity and facilitate the regeneration of infection wounds. Under NIR irradiation, the QP/QT-MB hydrogels exhibited a desirable mild photothermal effect and NIR-activity controllable NO delivery, combined with the endogenous contact antimicrobial activity of hydrogel, contributing jointly to induce dispersal of biofilms and disruption of the bacterial plasma membranes, ultimately leading to bacteria inactivation and biofilm elimination. In vivo experiments demonstrated that the fabricated QP/QT-MB hydrogel platform was capable of inducing efficient eradication of the S. aureus biofilm in a severely infected wound model and accelerating infected wound repair by promoting collagen deposition, angiogenesis, and suppressing inflammatory responses. Additionally, the QP/QT-MB hydrogel demonstrated excellent biocompatibility in vitro and in vivo. Collectively, the hydrogel (QP/QT-MB) reveals great potential application prospects as a promising alternative in the field of biofilm-associated infection treatment.

An electroconductive hydrogel with injectable and self-healing properties accelerates peripheral nerve regeneration and motor functional recovery

Peripheral nerve regeneration and functional recovery are slow due to disruption of bioelectrical signal transmission. As a new therapeutic strategy, conductive hydrogels have been shown to promote the regeneration of electroactive tissue, especially nerve tissue. However, conventional conductive hydrogels made of physically doped conductive particles suffer from fragility, agglomeration, poor durability, and discontinuous transmission of electrical signals, severely limiting the migration of Schwann cells (SCs) and the remyelination of axons. Herein, a novel water-soluble conductive material was synthesized by grafting polyaniline (PANI) onto carboxymethyl chitosan (CMCS). Dual cross-linked hydrogels with injectable, self-healing, and conductive properties were created by adding CMCS-PANI (CP) to the dynamic gel network generated by the Schiff base reaction between aldehyde-based hyaluronic acid (ALHA) and CMCS. The prepared self-healing ALHA/CMCS/CP (ACCP) hydrogel had good biocompatibility, elastic modulus, and electrical conductivity that matched the sciatic nerve. The in vitro experiments indicated that ACCP3 (3 wt% CP) promoted the proliferation and migration of the SCs. Injection of ACCP3 into the crush injury site of the sciatic nerve reduced tissue resistivity, increased nerve conduction velocity, decreased the sciatic nerve functional index, enhanced the expression of neuronal axon-specific proteins, induced axon extension and remyelination, and prevented muscle denervation atrophy. Overall, the injectable self-healing conductive ACCP3 hydrogel, as a safe and effective neural tissue substitute, opens up a new way for the treatment of peripheral nerve injury and has potential clinical application.

Thermoresponsive injectable self-healing hydrogel containing polydopamine-coated Fe/Mo-doped TiO2 nanoparticles for efficient synergistic sonodynamic-chemodynamic-photothermal-chemo therapy

A smart hydrogel loading multifunctional nanoparticles and anticancer drugs was designed to achieve synergistic therapy against tumors with high efficiency and specificity. The thermoresponsive injectable self-healing hydrogel was prepared through the Schiff base between aldehyde-functionalized poly(2-(2-methoxyethoxy) ethyl methacrylate)–co-oligo(ethylene glycol) methacrylate-co-2-hydroxyethyl methacrylate) (P(MEO2MA-co-OEGMA-co-HEMA), APMOH) and hydroxypropyl chitosan (HPCS). The polydopamine-coated Fe/Mo-doped titanium dioxide nanoparticles (PDA@dTiO2 NPs) were prepared and dispersed into the hydrogel with anticancer drug doxorubicin (DOX). PDA@dTiO2 NPs as sonosensitizers can convert oxygen into singlet oxygen (1O2) under ultrasound (US) irradiation, achieving sonodynamic therapy (SDT). They were also considered nanoenzymes, generating oxygen to supply an oxygen source for SDT, producing hydroxyl radical (·OH) to achieve chemodynamic therapy (CDT), and eliminating glutathione (GSH) to enhance the level of oxidative stress. After near-infrared (NIR) irradiation, the temperature of the hydrogel increased due to the photothermal ability of the polydopamine (PDA) layer. When the temperature reached the hydrogel's lower critical solution temperature (LCST), the hydrophilic-hydrophobic transformation occurred, and the hydrogel volume contracted. Consequently, the release rate of PDA@dTiO2 NPs and DOX increased, improving the therapeutic effects. The nanocomposite hydrogel system can achieve synergistic sonodynamic-chemodynamic-photothermal-chemo therapy (SDT-CDT-PTT-CT) for tumors, providing a novel platform for synergistic tumor treatment.

Incorporating copper-based nanosheets into an injectable self-healing hydrogel enables superb repair of infected diabetic wound

Continuous bleeding, bacterial infection, oxidative stress, and vascular damage within a diabetic wound microenvironment necessitate the development of multifunctional dressings that match the complex physiological process of skin healing. Herein, copper–tannic acid (CuTA) nanosheets were first synthesized by chelating copper ions with tannic acid (TA). These nanosheets were subsequently integrated into an injectable self-healing hydrogel comprising methacrylic anhydride-modified gelatin (GelMA), cationic guar gum (CG), and borax. Through free-radical polymerization as well as hydrogen and borate ester bonds formation, we fabricated an acidic and highly reactive oxygen species (ROS)-responsive composite hydrogel named GGB-CT, which exhibited remarkable hemostasis and adhesion. With responsive decomposition of GGB-CT, the released CuTA efficiently scavenged excess ROS as well as effectively killed bacteria by inhibiting arginine synthesis, blocking the tricarboxylic acid cycle and inducing cuproptosis-like death in the tested microbes. In the later stages of wound healing, the composite hydrogel substantially promoted macrophage polarization and angiogenesis, thus accelerating the re-epithelialization of the wound area. Overall, this study proposes an innovative hydrogel for treating infected diabetic wounds and may inspire new thinking of high-performance hydrogels for biomedical applications.

A temperature and pH dual-responsive injectable self-healing hydrogel prepared by chitosan oligosaccharide and aldehyde hyaluronic acid for promoting diabetic foot ulcer healing

Chronic wound, such as skin defect after burn, pressure ulcer, and diabetic foot ulcer is very difficult to cure. Its pathological process is often accompanied with local temperature rise, pH decrease, and other phenomena. Owing to their outstanding hydrophilic, biocompatibility, and responsive properties, hydrogels could accelerate the healing process. In this study, we chose chitosan oligosaccharide (COS) grafted with Pluronic F127 (F127-COS). Aldehyde hyaluronic acid (A-HA) oxidized by NaIO4. And added boric acid (BA) to prepare a thermosensitive and pH-responsive injectable self-healing F127-COS/A-HA/COS/BA (FCAB) hydrogel, loaded with drug deferoxamine (DFO) in order to have an accurate release and promote angiogenesis of diabetic foot ulcer. In vitro experiments had verified that the FCAB hydrogel system loaded with DFO (FCAB/D) could promote migration and angiogenesis of HUVEC. A diabetes rat back wound model further confirmed its role in promoting angiogenesis in wound repair process. The results showed that the FCAB/D hydrogel exhibited unique physicochemical properties, excellent biocompatibility, and significantly enhanced therapeutic effects for diabetic foot ulcer.

Carboxymethylcellulose based self-healing hydrogel with coupled DOX as Camptothecin loading carrier for synergetic colon cancer treatment

The self-healing hydrogels have important applications in biomedication as drug release carrier. In this research, the Doxorubicin (DOX) was coupled onto oxidized carboxymethylcellulose (CMC) (CMC-Ald) to fabricate self-healing hydrogel with intrinsic antitumor property and loaded with Camptothecin (CPT) for synergetic antitumor treatment. The DOX coupled CMC-Ald (CMC-AD) was reacted with poly(aspartic hydrazide) (PAH) to fabricate injectable self-healing hydrogel. The coupled DOX avoided the burst release of the drug and the 100 % CPT loaded hydrogel could take the advantages of both drugs to enhance the synergetic antitumor therapeutic effect. The in vitro and in vivo results revealed the CPT loaded CMC-AD/PAH hydrogel showed enhanced antitumor property and reduced biotoxicity of the drugs. These properties demonstrate that the CMC-AD/PAH hydrogel has great application prospects in biomedication.

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.

Multifunctional antibacterial bioactive nanoglass hydrogel for normal and MRSA infected wound repair

Large-scale skin damage brings potential risk to patients, such as imbalance of skin homeostasis, inflammation, fluid loss and bacterial infection. Moreover, multidrug resistant bacteria (MDRB) infection is still a great challenge for skin damage repair. Herein, we developed an injectable self-healing bioactive nanoglass hydrogel (FABA) with robust antibacterial and anti-inflammatory ability for normal and Methicillin-resistant Staphylococcus aureus (MRSA) infected skin wound repair. FABA hydrogel was fabricated facilely by the self-crosslinking of F127-CHO (FA) and alendronate sodium (AL)-decorated Si-Ca-Cu nanoglass (BA). FABA hydrogel could significantly inhibit the growth of Staphylococcus aureus, Escherichia coli and MRSA in vitro, while showing good cytocompatibility and hemocompatibility. In addition, FABA hydrogel could inhibit the expression of proinflammatory factor TNF-α and enhance the expression of anti-inflammatory factor IL-4/ IL-10. Based on its versatility, FABA hydrogel could complete wound closure efficiently (75% at day 3 for normal wound, 70% at day 3 for MRSA wound), which was almost 3 times higher than control wound, which was related with the decrease of inflammatory factor in early wound. This work suggested that FABA hydrogel could be a promising dressing for acute and MRSA-infected wound repair.Graphical

Injectable Self-Healing Adhesive Natural Glycyrrhizic Acid Bioactive Hydrogel for Bacteria-Infected Wound Healing

Bioactive hydrogels self-assembled from naturally occurring herbal small molecules are attracting growing interest for applications in wound healing, due to their versatile intrinsic biological activities, excellent biocompatibility, as well as facile, sustainable, and eco-friendly processes. However, the development of supramolecular herb hydrogels with sufficient strength and multifunctionality as an ideal wound dressing in clinical practice remains a challenge. In this work, inspired by the efficient clinic therapy and directed self-assembly of natural saponin glycyrrhizic acid (GA), we create a novel GA-based hybrid hydrogel to promote full-thickness wound healing and bacterial-infected wound healing. This hydrogel possesses excellent stability and mechanical performance and multifunctional properties, including injectable, shape-adaptation and remodeling, self-healing, and adhesive abilities. This is attributed to the hierarchical dual-network that comprises the self-assembled hydrogen-bond fibrillar network of aldehyde-contained GA (AGA) and the dynamic covalent network through Schiff base reaction between AGA and a biopolymer carboxymethyl chitosan (CMC). Notably, benefiting from the inherent strong biological activity of GA, the AGA-CMC hybrid hydrogel exhibits unique and significant anti-inflammation effects and antibacterial ability, especially toward the Gram-positive Staphylococcus aureus (S. aureus). In vivo experiments demonstrate that the AGA-CMC hydrogel promotes uninfected skin wound healing and S. aureus-infected skin wound healing by enhancing the formation of granulation tissue, facilitating collagen deposition, reducing bacterial infection, and downregulating inflammatory response. This study highlights the design of new and multifunctional bioactive herb hydrogels from natural drug-food homologous small molecules, which can serve as a promising wound-healing dressing for biomedical applications.

Exosome-laden injectable self-healing hydrogel based on quaternized chitosan and oxidized starch attenuates disc degeneration by suppressing nucleus pulposus senescence

Disc degeneration is the common pathology underlying various degenerative spinal disorders and currently there is no effective cure. Here, we found nucleus pulposus (NP) cell senescence was closely associated with the severity of disc degeneration, and exosomes (Exos) derived from mesenchymal stem cells (MSCs) ameliorated NP cell senescence and promoted extracellular matrix (ECM) deposition. As chitosan-based hydrogels have been widely used as vehicles to deliver Exos due to their prominent antibacterial capacity, biocompatibility, and biodegradability, we developed an Exos-laden hydrogel based on quaternized chitosan (QCS) and oxidized starch (OST) to treat disc degeneration. The synthesized QCS-OST hydrogel is injectable, self-healing, biocompatible, and demonstrated desirable pore size, injectable properties, and sustainable release of Exos. In a rat model of disc degeneration, the QCS-OST/Exos hydrogel was able to rejuvenate NP cell senescence, promote ECM remodeling, and partially restore the structures of NP and annulus fibrosis. Our findings suggested that the novel QCS-OST/Exos hydrogel is an effective therapeutic strategy for treating disc degeneration via alleviating NP cell senescence.

The preparation and characterization of self-healing hydrogels based on polypeptides with a dual response to light and hydrogen peroxide

An injectable self-healing polypeptide-based hydrogel that is responsive to hydrogen peroxide and light is prepared. The controlled release of hydrophobic drug molecules at specific sites, such as tumor tissues, was accordingly achieved.

A Choline Phosphoryl-Conjugated Chitosan/Oxidized Dextran Injectable Self-Healing Hydrogel for Improved Hemostatic Efficacy.

The development of injectable hydrogels with good biocompatibility, self-healing, and superior hemostatic properties is highly desirable in emergency and clinical applications. Herein, we report an in situ injectable and self-healing hemostatic hydrogel based on choline phosphoryl functionalized chitosan (CS-g-CP) and oxidized dextran (ODex). The CP groups were hypothesized to accelerate hemostasis by facilitating erythrocyte adhesion and aggregation. Our results reveal that the CS-g-CP/ODex hydrogels exhibit enhanced blood clotting and erythrocyte adhesion/aggregation capacities compared to those of the CS/ODex hydrogels. The CS-g-CP50/ODex75 hydrogel presents rapid gelation time, good mechanical strength and tissue adhesiveness, satisfactory bursting pressure, and favorable biocompatibility. The hemostatic ability of the CS-g-CP50/ODex75 hydrogel was significantly improved compared to that of the CS/ODex hydrogel and commercial fibrin sealant in the rat tail amputation and liver/spleen injury models. Our study highlights the positive and synergistic effects of CP groups on hemostasis and strongly supports the CS-g-CP50/ODex75 hydrogel as a promising adhesive for hemorrhage control.

Injectable self-healing polysaccharide hydrogel loading CuS and pH-responsive DOX@ZIF-8 nanoparticles for synergistic photothermal-photodynamic-chemo therapy of cancer

The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose (MCCHO) and carboxymethyl chitosan (CMC). The copper sulfide nanoparticles (CuS NPs) and pH-sensitive doxorubicin-loaded zeolitic imidazolate frameworks nanoparticles ([email protected] NPs) were prepared and could be well-dispersed into the hydrogel system. The presence of CuS NPs can achieve photothermal therapy (PTT) for tumors under the irradiation of the near-infrared (NIR) laser. Moreover, CuS NPs can generate photodynamic effects under NIR irradiation, converting oxygen into toxic reactive oxygen species (ROS) and presenting efficient photodynamic therapy (PDT). The [email protected] NPs can be decomposed under an intracellular acidic environment and realize the controlled release of DOX. The injectable self-healing hydrogel loading CuS and [email protected] NPs can achieve synergistic photothermal-photodynamic-chemo therapy for tumors and will inspire the researchers to construct a platform from hydrogel combined with multifunctional nanomaterials to realize the effective multimodal therapy for tumor.

Enhancing cartilage repair with optimized supramolecular hydrogel-based scaffold and pulsed electromagnetic field.

Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage. Hydrogel is widely used because it could provide rapid defect filling and proper structure support, and is biocompatible for cell aggregation and matrix deposition. Efforts have been made to seek suitable scaffolds for cartilage tissue engineering. Here Alg-DA/Ac-β-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties. Gelation time, swelling ratio, biodegradability and biocompatibility of the hydrogels were systematically characterized, and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair. Furthermore, the new hydrogel design introduces a pre-gel state before photo-crosslinking, where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition. This granted multiple administration routes to the hydrogels, which brings hydrogels the ability to adapt to complex clinical situations. Pulsed electromagnetic fields (PEMF) have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials. PEMF treatment offers a better clinical outcome with fewer, if any, side effects, and wildly used in musculoskeletal tissue repair. Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering. In this study, the as-prepared Alg-DA/Ac-β-CD/gelatin hydrogels were utilized in the rat osteochondral defect model, and the potential application of PEMF in cartilage tissue engineering were investigated. PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro, and facilitate chondrogenesis and cartilage repair in vivo. All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment, this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.