ABSTRACT Bioelectronic interfaces necessitate devices that not only align mechanically with biological tissues but also adhere effectively to wet surfaces and maintain electrochemical stability over extended periods. However, glycolated conjugated polymer (g‐CP) channels in organic electrochemical transistors (OECTs) face challenges due to mechanical incompatibility and swelling‐induced degradation. We propose a versatile interfacial design employing a conformal hydrogel coating that transforms various p‐type and n‐type g‐CPs into bioelectronic interfaces that can harmonize with tissue and maintain adhesion. This innovative coating ensures seamless interaction between the device and biological tissues, while concurrently mitigating channel swelling. As a result, the coated OECTs exhibit a figure‐of‐merit µ C* roughly double that of uncoated OECTs and show enhanced stability over 1800 operational cycles. When utilized within a flexible, complementary circuit, these coated OECTs deliver a substantial voltage gain of 210 V V −1 and consume an exceptionally low power of 20 nW. Validated through in vivo electrocorticographic recordings, the platform achieves a signal‐to‐noise ratio of 28 dB—significantly surpassing that of conventional electrodes—highlighting its potential for high‐fidelity neural interfacing. This study elegantly combines the mechanics of soft hydrogels with the superior performance of organic electronics through deliberate interface engineering, providing a comprehensive strategy for cutting‐edge biointegration.
The therapeutic efficacy of melanoma immunochemotherapy is severely limited by insufficient intratumoral drug retention, systemic toxicity, and immunosuppressive tumor microenvironment (TME). Thus, we developed a single-dose injectable localized chemo-immunotherapy platform that enables sustained tumor-restricted delivery and synergistic immune remodeling. This hybrid system integrates doxorubicin-loaded tumor-derived exosome-coated hollow mesoporous silica nanoparticles (DeH) with a mannose-modified β-cyclodextrin-polyethyleneimine carrier co-delivering dual Toll-like receptor agonists (RC-MCP) within a thermoresponsive polypeptide hydrogel (mPEG-b-PELG). The biomimetic exosome coating provides an exosome-sheathed nanostructure and amplifies doxorubicin-induced immunogenic cell death. Mannose-mediated targeting facilitates preferential uptake by antigen-presenting cells and enhances endosomal Toll-like receptor signaling, leading to robust dendritic cell maturation. Following intratumoral injection, the hydrogel undergoes in situ sol-gel transition to form a stable drug depot, enabling sustained and coordinated release while minimizing systemic exposure. As a result, a single intratumoral administration elicits potent antitumor immune responses, significantly suppresses tumor growth, alleviates TME immunosuppression, and exhibits favorable biocompatibility in murine melanoma model. Collectively, this work presents a rationally designed single-dose localized chemo-immunotherapy strategy for melanoma treatment.
Cancer immunotherapy is an emerging therapeutic approach that demonstrates superior immune specificity and reduced off-target effects compared to conventional chemotherapy, radiotherapy and surgery. Cancer vaccines are a promising immunotherapeutic strategy, though their clinical application faces limitations including inefficient antigen presentation, inadequate immunogenicity, and failure to establish an effective, durable immune microenvironment in vivo. To address these issues, we developed a physically and chemically dual-crosslinked hydrogel vaccine delivery system. Leveraging its unique differential degradation properties, this system enabled the sustained release of three critical immunostimulants, including tumor antigens, granulocyte macrophage-colony stimulating factor, and resiquimod-loaded nanoparticles. Simultaneously, it formed a three-dimensional scaffold at the injection site with dynamically expanding porous structures induced by degradation. This efficiently recruited and reprogramed innate immune cells. This hydrogel vaccine established a long-lasting immune activating site at the injection site. In both prophylactic and post-surgical tumor recurrence models, the gel vaccine successfully induced significant and sustained antigen-specific immune responses, effectively suppressing tumor growth. This study developed an in situ immune cell reprogramming cancer vaccine capable of providing long-term immune protection against tumor growth and recurrence.
Chemo-immunotherapy has been an emerging synergistic strategy for melanoma treatment. However, major challenges still remain, including side effects of chemotherapeutic agents and insufficient efficacy of immunotherapy. In the present work, we designed a thermosensitive polypeptide hydrogel-based drug delivery system to achieve the codelivery of doxorubicin (DOX) and a Toll-like receptor (TLR)-9 agonist, CpG. The hydrogel system was engineered by incorporating cancer cell membrane enveloped hollow mesoporous silica loaded with DOX and the mPEG-ss-PEI/CpG nanocomplex, resulting in an enhanced therapeutic effect. Drug-loaded hydrogel system exhibited sustained drug release, enhanced immune cell activation, and induction of immunogenic cell death (ICD) of tumor cells. In vivo antitumor studies revealed that the drug-loaded hydrogel effectively inhibited tumor growth, and promoted expansion of CD8+ T cells and maturation of dendritic cells (DCs), facilitating favorable modulation of the tumor microenvironment. Hence, the developed drug-loaded hydrogel system has considerable potential as a platform for combinatorial chemo-immunotherapy in melanoma treatment.
ABSTRACT The treatment of diabetic wounds remains a major challenge due to persistent bacterial infections, chronic inflammation, and impaired angiogenesis. To address these issues, we develop an immunomodulatory and antibacterial hydrogel integrating epidermal growth factor (EGF)‐loaded liposomes for efficiently accelerating diabetic wound healing. The hydrogel is formed through the crosslinking reaction between gallic acid‐modified ε‐poly‐L‐lysine (ε‐PLL‐GA) and o ‐phthalaldehyde‐functionalized four‐arm polyethylene glycol (4aPEG‐OPA). The hydrogel exhibits robust broad‐spectrum antimicrobial properties, and achieves a bacterial inhibition rate of 99.9% in a subcutaneous infection model. The hydrogel exhibits prominent antioxidative and reactive oxygen species (ROS) scavenging properties, and demonstrates immunomodulatory M2‐inducing effects on macrophages. Moreover, sustained release of EGF from the liposome‐incorporated hydrogel system promotes cell migration and tube formation of human umbilical vein endothelial cells. The immunomodulatory, antibacterial and EGF‐releasing hydrogel demonstrates remarkably improved wound healing efficacy in both diabetic foot ulcer and bacteria‐infected diabetic wound models by remodeling the wound microenvironment. These findings present strong potential of the multifunctional hydrogel for the effective treatment of complicated chronic wounds such as diabetic wounds and infected wounds.
Cancer therapy and regenerative medicine still face significant clinical challenges, urgently requiring advanced strategies capable of precisely delivering therapeutic drugs and effectively modulating the pathological microenvironment. Cell-derived nanocarriers demonstrate potential in drug delivery due to their inherent biocompatibility, low immunogenicity, and specific targeting capabilities. However, in vivo applications of free cell-derived nanocarriers are often limited by rapid clearance from the bloodstream, short retention times at target sites, and susceptibility to inactivation of bioactive components. To overcome these limitations, incorporating cell-derived nanocarriers in injectable hydrogels to construct composite platform has shown remarkable potential in biomaterials fields. This review provides a comprehensive overview of the integration of hydrogel networks with diverse bioactive nanocarriers. Specifically, we compare the unique features of various nanocarriers and the advantages and limitations of different hydrogel crosslinking strategies. Furthermore, we highlight the key roles of the hydrogel platforms, such as preserving the bioactivity of nanocarriers, elevating local concentrations of nanocarriers, and enabling controlled payload release in situ. The construction strategies for the nanocarrier-incorporated hydrogel systems are discussed, ranging from physical encapsulation to dynamic chemical bond anchoring of the nanocarriers. Subsequently, the applications in tumor therapy and regenerative medicine are emphasized. Finally, the challenges and future directions in standardized production, precise release regulation, and clinical translation of the composite hydrogel systems are discussed in detail.
The impact of chirality on immune response has attracted great interest in cancer vaccine research recently. However, the study of chiral synthetic polypeptide hydrogels as cancer vaccines as well as of the impact of biomaterials themselves for antitumor immunotherapy has rarely been reported. Here, we show the key role of residue chirality of polypeptide hydrogels in antitumor immunity and local immune microenvironment regulation. Compared to poly(γ-ethyl-L-glutamate)-based hydrogels (L-Gel), poly(γ-ethyl-D-glutamate)-based hydrogels (D-Gel) induces enhanced level of immune cell infiltration. However, D-Gel causes higher levels of suppressive markers on antigen-presenting cells and even induces stronger T cell exhaustion than L-Gel. Finally, D-Gel establishes a local chronic inflammatory and immunosuppressive microenvironment and shows insufficient anti-tumor effects. Conversely, the milder host immune responses induced by L-Gel leads to more effective tumor inhibition. This study provides insights on the role of residue chirality in the regulation of local immune microenvironment and affecting antitumor immune response. The impact of chemical chirality on immune response attracts attention in cancer vaccine design recently. Here this group reports the chirality of poly(γ-ethyl-D-glutamate)-based hydrogel exhibiting higher levels of suppression on antigen-presenting cells and inducing stronger T cell exhaustion than L-Gel eventually leading to insufficient anti-tumor efficacy.
Effective treatment of diabetic wounds remains challenging because of multidrug-resistant (MDR) bacterial infections, excessive oxidative stress, and impaired angiogenesis. In this study, a tissue-adhesive and antibacterial hydrogel incorporating MXene and deferoxamine (DFO)-loaded microspheres is developed for the treatment of MDR bacteria-infected diabetic wounds. The hydrogel is built based on covalent crosslinking between ε-poly(L-lysine) and o-phthalaldehyde-terminated four-arm poly(ethylene glycol). The hydrogel exhibited excellent mechanical properties, tissue adhesion strength, biocompatibility, and biodegradability. Under near-infrared (NIR) irradiation, the MXene converted light into heat and elevated the local temperature rapidly, enabling the rapid disintegration of MDR bacterial biofilms. Simultaneously, the hydrogel exerted inherent antibacterial activity, persistently killing planktonic bacteria, and effectively controlling wound infections. The encapsulated DFO is then released from the hydrogel in a sustained and controlled manner, and promoted angiogenesis during diabetic wound healing. Additionally, MXenes can scavenge excessive reactive oxygen species and alleviate wound inflammation. In the methicillin-resistant Staphylococcus aureus-infected diabetic wound model in mice, the composite hydrogel along with NIR irradiation efficiently reduced the infectious bacteria, and accelerated the wound healing by promoting angiogenesis and alleviating inflammation. This composite hydrogel has great clinical potential for the treatment of diabetic wounds, particularly in challenging healing environments involving motion and infection.
ObjectiveTo develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.MethodsA fluorescein-labeled polyglutamic acid-based polyamino acid dexamethasone nanohydrogel was synthesized, and its gelation time was measured. The hydrogel was surgically injected into the round window niche of guinea pigs to determine its degradation time in the middle ear cavity in vivo. The safety, pharmacokinetics, and distribution patterns of dexamethasone in the inner ear were evaluated.ResultsThe hydrogel exhibited a gelation time of 80 seconds in a 37℃ water bath. In vivo, the hydrogel was almost completely degraded within 7 days in the middle ear cavity of guinea pigs. Transient hearing loss was observed one day after administration, but hearing gradually returned to normal over time. No significant cytotoxicity, vestibular stimulation signs, or pathological abnormalities in spiral ganglion cells were observed. Histopathological examination revealed no significant inflammatory reactions. Pharmacokinetic analysis demonstrated sustained drug release and prolonged dexamethasone activity. Immunofluorescence staining confirmed the distribution of dexamethasone in both the cochlea and vestibular organs.ConclusionThe polyamino acid nanohydrogel exhibits excellent injectability and biodegradability, representing a safe and effective drug delivery system for the inner ear.
Despite its advances, the clinical efficacy of cancer immunotherapy remains limited due to inefficient immune response rate, high systemic toxicity, and the immunosuppressive nature of the tumor microenvironment (TME). Due to their three-dimensional mesh structure, hydrogels provide an effective platform for the local delivery of therapeutic drugs. Herein, we report a matrix metalloproteinase (MMP)-responsive poly(L-glutamic acid) hydrogel co-loaded with oxaliplatin (OXA) and DC-targeting resiquimod (R848)-encapsulated nanoparticles (R@pep-PNP) to address these challenges. The hydrogel had TME-specific degradation and sustained drug release capacity due to its MMP-cross-linked network. OXA released from the hydrogel could induce immunogenic cell death (ICD) in tumor cells and the generation of tumor antigens, while R848 released from the DC-targeting nanoparticles promoted DCs maturation and lymph node draining. In mouse melanoma models, the hydrogel co-loaded with OXA and R@pep-PNP elicited a robust systemic anti-tumor immune response, effectively inhibited tumor growth and recurrence, and established a durable immune memory. Additionally, the treatment with the drug-loaded hydrogel resulted in minimal systemic side effects. Overall, this study presents an efficient hydrogel platform for overcoming immunosuppressive barriers and enhancing anti-tumor immunity.
Tissue adhesives have become substitutes or adjuvants for surgical sutures owing to their minimal tissue damage and ease of application. However, limitations remain for existing tissue adhesives, such as weak adhesion strength, potential toxicity, and lack of bioactivities to promote wound healing. Here, we developed an injectable and biocompatible hydrogel tissue adhesive incorporating basic fibroblast growth factor (bFGF)-loaded liposomes for sutureless wound closure and promoting wound healing. The hydrogel, formed by 10 %(w/v) human serum albumin (HSA) and o-phthalaldehyde (OPA)-functionalized four-arm poly(ethylene glycol) (4aPEG-OPA) through irreversible OPA/amine condensation reaction, demonstrated strong tissue adhesion properties, biodegradability (complete degradation in PBS containing 1 U/mL elastase within 10 days), and biocompatibility. The hydrogel incorporating bFGF-loaded liposomes achieved sustained release of bFGF (cumulative release ratio of 65.4 % over 8 days), and promoted cell proliferation, migration, collagen production, and angiogenesis. In rat and porcine full-thickness skin incision models, the hydrogel effectively closed the wounds and facilitated wound healing within 14 days, outperforming commercially available fibrin glue and cyanoacrylate adhesives. RNA sequencing and western blotting analysis demonstrated that the hydrogel stimulated cell proliferation, collagen production, and angiogenesis. Overall, this hydrogel tissue adhesive shows great potential for encouraging wound closure without suture and promoting wound healing. STATEMENT OF SIGNIFICANCE: This study introduces a multifunctional tissue-adhesive hydrogel formed by covalent cross-linking of human serum albumin with o-phthalaldehyde (OPA)-terminated four-arm poly(ethylene glycol), and incorporated with bFGF-loaded liposomes. The catalyst-free OPA/amine reaction used in its synthesis ensures a mild and controllable gelation process, which is beneficial for maintaining the bioactivity of encapsulated growth factors. This composite system exhibited sustained growth factor release profile and remarkable bioactivity in regulating skin cell behaviors, which facilitates easier clinical translation compared to existing approaches. In rat and porcine models, it achieved sutureless wound healing and outperformed commercial adhesives in promoting re-epithelialization and angiogenesis, offering a promising alternative to traditional sutures and commercial adhesives.
Immunotherapy is a promising cancer treatment with great clinical success. However, its low response rate for many types of cancers is still a limitation owing to the tumor immunosuppressive microenvironment. Herein, an iron-based nanoscale metal-organic framework (MOF) is constructed as a drug carrier with immune-stimulating activity. After reduction and maleimide grafting of basic NH2-MIL-88B, the synthesized MOF (rMOF-MA) dramatically increases the production of reactive oxygen species. Accompanied with a high amount of intracellular iron accumulation originating from endocytosis by macrophages, rMOF-MA thus promotes the polarization of macrophages from anti-inflammatory M2 to pro-inflammatory M1 for reprogramming the tumor microenvironment and enhancing immune response. After loading with immune adjuvant resiquimod (R848) and further encapsulation by a tissue-adhesive hydrogel, a local inflammatory niche is constructed. When further combined with immune checkpoint blockade (ICB) therapy, the hydrogel-based combination immunotherapy exhibits strengthened systemic antitumor immunity and significantly inhibits tumor growth, lung metastasis, and tumor recurrence after surgery. Therefore, this MOF-based immune-regulating depot exhibits potential as a promising agent for clinical cancer immunotherapy.
Background: The potential of injectable hydrogels as drug depots lies in their ability to achieve local and sustained co-delivery of chemotherapeutic drugs and immunostimulants for combined tumor therapy. Method: In this study, we devised a localized chemo-immunotherapeutic strategy by co-loading the chemotherapeutic drug, oxaliplatin (OXA), and the immune-checkpoint blockade (ICB) antibody, anti-programmed cell death protein ligand 1 (anti-PD-L1), into a matrix metalloproteinase (MMP)-responsive injectable poly(L-glutamic acid) hydrogel (MMP-gel). Results: The in situ gelation of hydrogels enables local retention of OXA and model antibody IgG, as well as MMP-triggered sustained release. Meanwhile, the OXA-loaded MMP-gel caused the immunogenic cell death (ICD) of tumor cells. When administered intratumorally in mice carrying B16F10 melanoma, the MMP-gel co-loaded with OXA and anti-PD-L1 (OXA&anti-PD-L1@MMP-gel) demonstrated superior tumor suppression efficacy and prolonged the survival time of the animals with low systemic toxicity. Meanwhile, the OXA&anti-PD-L1@MMP-gel induced an increase in CD8+ T cells and M1 macrophages within tumors, and a decrease in Treg cells and M2 macrophages, demonstrating that the drug-loaded system enhanced the antitumor immune response. Moreover, the OXA&anti-PD-L1@MMP-gel effectively inhibited the growth of distal tumors in a bilateral-tumor experiment. Conclusions: Consequently, the responsive hydrogel-based chemo-immunotherapy holds potential in tumor treatment.
Triple-negative breast cancer (TNBC), characterized by its heterogeneity and poor clinical prognosis, presents substantial unmet medical needs. Although exciting progress has been made in immunotherapy for TNBC, optimizing the composition of immune cells within the tumor microenvironment (TME) remains a critical challenge. In this study, we demonstrate that CCL25-transduced tumor cells significantly enhance the accumulation of CCR9+CD8+T cells within tumors, translating into inhibited TNBC tumor growth in vivo. To further exploit this mechanism, we developed an injectable, thermo-responsive hydrogel loaded with CCL25 for intratumoral delivery, aimed at recruiting CCR9+ cells into the TME. Our results revealed that the influence of CCL25 on the TME is both dose- and time-dependent, mediated through the precise regulation of CCR9+ cells infiltration into tumor tissues. Furthermore, CCL25-loaded hydrogel, when administered at an appropriate dose and timing, could enhance the therapeutic response to PD-1 inhibitors, credited to the activation of a T cell-dependent antitumor immunity. This innovative approach not only provides deeper insights into the role of the chemokine system in tumor biology but also suggests a promising strategy for enhancing the efficacy of TNBC immunotherapy. The potential of hydrogel-based chemokine delivery systems to remodel the TME could have significant implications for future cancer treatment. STATEMENT OF SIGNIFICANCE: In our study, we developed a thermo-responsive injectable hydrogel for intratumoral delivery of CCL25. Our findings demonstrate that CCL25@gel promotes the infiltration of CCR9+CD8+T cells into the tumor microenvironment in a dose- and time-dependent manner. Notably, at an optimal dose and administration schedule, CCL25@gel significantly enhances the therapeutic response to PD-1 inhibitors, thereby improving the efficacy of immunotherapy in triple-negative breast cancer (TNBC). These results highlight the potential of CCL25 in modulating the immune landscape of the tumor microenvironment and emphasize the importance of optimizing key delivery parameters-dose, timing, and frequency-to maximize therapeutic benefits. Moreover, this work provides valuable insights into chemokine-based immunotherapy for TNBC, offering new avenues for more effective treatment strategies.
Diabetic wounds, a major complication of diabetes mellitus, pose a significant clinical challenge. The treatment of diabetic wounds requires comprehensive interventions tailored to their pathophysiological characteristics, such as recurring bacterial infection, persistent inflammation, excessive oxidative stress, and impaired angiogenesis. The development of stimulus-responsive hydrogel dressings offers new strategies for diabetic wound treatment. By responding to various physical and biochemical signals, these smart hydrogels enable real-time monitoring and precise modulation of the wound microenvironment to accelerate diabetic wound healing. In this review, we provide an overview of the disease characteristics of chronic diabetic wounds and introduce the current clinical treatment approaches. We summarize the cutting-edge applications of physical and biochemical signal-responsive hydrogels for diabetic wound treatment by modulating the wound microenvironment.
Asthma is a chronic disease with typical pathological features such as airflow limitation, airway inflammation and remodeling. Of these, neutrophilic asthma is considered to be the more severe and corticosteroid-resistant subtype of asthma. Increasing evidence suggests that patients with neutrophilic asthma often accompany with dysbiosis of the internal microbiota, where the increased abundance of non-typeable Haemophilus influenzae (NTHi) is closely related to the neutrophilic asthma phenotype. Furthermore, emerging evidence suggests that reactive oxygen species (ROS) are pivotal in the pathogenesis of neutrophilic asthma. In this study, matrix metalloproteinase-9 (MMP-9)-responsive, catalase-loaded nanogels (M-CAT-NGs) were synthesized, which was composed of MMP-9-sensitive peptide (VPMS), arginine-grafted chitosan and maleimide (CS-Arg-Mal), catalase (CAT), sodium citrate (SC) and ε-poly(L-lysine) (ε-PLL). The M-CAT-NGs showed potent antimicrobial effects and exerted excellent therapeutic effects in the presence of MMP-9 by causing VPMS rupture and responsive release of CAT. In vitro experiments revealed that M-CAT-NGs effectively inhibited the proliferation of NTHi, Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli), while also demonstrating the capacity to modulate the inflammatory response induced by lipopolysaccharide (LPS) and hydrogen peroxide (H2O2) stimulation. In vivo experiments demonstrated that nebulized inhalation of M-CAT-NGs was effective in reducing airway hyperresponsiveness (AHR), alleviating inflammation, downregulating the expression level of ROS in the lung tissues, thus enabling the effective management of neutrophilic asthma. Thus, the development of M-CAT-NGs has shown strong potential for the clinical management of neutrophilic asthma by modulating the inflammatory response.
The abdominal cavity houses the majority of the digestive system organs, which frequently suffer from diseases with limited responsiveness to pharmacological treatments, such as bleeding, perforation, cancer, and mechanical obstruction. Invasive procedures, including endoscopy and surgery, are typically employed to manage these conditions. Currently, sutures and staplers remain the gold standard for internal wound closure. However, these methods inevitably cause secondary tissue damage. Unlike superficial organs such as the skin, the abdominal cavity presents a relatively confined environment where postoperative complications tend to be more severe. To achieve wound closure and repair, hydrogel adhesives have garnered attention due to their minimal invasiveness, robust sealing, and ease of application. Nonetheless, the application of hydrogel adhesives within the abdominal cavity faces several challenges, including adhesion in moist environments, selective adhesion, and resistance to acids and digestive enzymes. To date, there has been no comprehensive review focused on the use of hydrogel adhesives for wound closure in abdominal digestive organs. This review introduces the design principles of hydrogel adhesives tailored for abdominal organs and provides a detailed overview of recent advances in their applications for esophageal endoscopic submucosal dissection, gastric perforation, hepatic bleeding, pancreatic leakage, and intestinal anastomotic leakage. Additionally, the current challenges and future directions of hydrogel adhesives are discussed. This review aims to provide valuable insights for the development of next-generation hydrogel adhesives for wound closure and repair in abdominal digestive organs.
Surgical treatment of colorectal diseases typically involves excising the diseased portion of the bowel and anastomosing the remaining sections to reestablish continuity. Surgical suturing has limitations in preventing anastomotic leakage and postoperative adhesion. To address these challenges, a tissue-adhesive, antibacterial, and antioxidant hydrogel is designed to cover and seal colorectal anastomotic wounds. The hydrogel is formed in situ by simply mixing oxidized hyaluronic acid, adipic acid dihydrazide-modified hyaluronic acid, ε-poly-l-lysine, and tannic acid. The hydrogel exhibits a rapid gelation rate and self-healing ability. Compared with commercial fibrin glue, the hydrogel has superior tissue-adhesive strength and wound sealing performance. The hydrogel displays potent reactive oxygen species scavenging ability and antibacterial activity against both Gram-positive and Gram-negative bacteria. The hydrogel also exhibits good biodegradation and biocompatibility. In a cecum-abdominal wall adhesion model in rats, the hydrogel attaches firmly to the injured tissues and serves as a physical barrier to prevent adhesion formation. In anastomotic leakage models after colon resection in rats and rabbits, the hydrogel effectively seals the anastomotic leakage, prevents postoperative adhesion, and promotes anastomotic healing. Thus, this multifunctional hydrogel has strong clinical potential for preventing anastomotic leakage and adhesion formation after colorectal surgery.
Diabetic foot ulcer has become a heavy burden to the healthcare system with the high and growing incidence of diabetes. Persistent bacterial infections in diabetic wounds can lead to chronic inflammation and delayed wound healing. To address these challenges, a dual‐crosslinked antibacterial hydrogel loaded with anti‐inflammatory compound asiaticoside is developed in this study. The hydrogel demonstrated suitable gelation properties, good biocompatibility, and exceptional antibacterial activity. In a diabetic foot ulcer model on rats, the asiaticoside‐loaded hydrogel can alleviate inflammation, promote angiogenesis, and accelerate wound healing. Therefore, this asiaticoside‐loaded antibacterial hydrogel shows considerable potential for diabetic wound healing.