Due to constant stimulation by stomach acid and local bleeding, gastric tissue wounds tend to heal slowly and complications such as anastomotic leakage have a high incidence. Suturing is often used to treat gastric wounds in clinic, but it still faces risks such as bleeding, slow healing, and leakage. Recently, hydrogel have been widely used to treat various types of wounds. Although hydrogels have shown promising efficacy in wound healing, it is still a challenge in dealing with wounds in gastric tissue for the poor adaptability of traditional materials in acidic environments. Hence, a series of pH responsive and good tissue adhesive hydrogels (MA-HA/AA) based on methacryloyl hyaluronic acid (MA-HA) and acryloyl-6-aminocaproic acid (AA) via in situ photo-crosslinking were designed, and anti-inflammatory and pro-healing traditional Chinese medicines ginsenoside Rg1 was incorporated into the hydrogel to treat gastric tissue wound. These acid-responsive hydrogels could form effective acid-resistant barriers and could lead to hemostasis rapidly through its strong adhesion. Besides, the hydrogels contracted under an acidic environment, which could tighten the gastric tissue wounds and sustained release the loaded ginsenoside Rg1. In addition, the hydrogels showed excellent biocompatibility and in vivo degradability. In summary, the acid-responsive contractile hyaluronic acid hydrogel loaded with ginsenoside Rg1 had good properties for hemostasis and acid-resistance to facilitate the promotion of gastric wounds healing.

Dry eye disease (DED) affects up to 50 % of the global population, leading to serious discomforts that affect patients' quality of life. In the multifactorial etiology of DED, oxidative stress is at the core, initiating a sequence of inflammatory responses and surface damage via a vicious cycle. However, current therapies merely have a narrow focus on inflammation. In this study, we developed a novel antioxidative eye drop, ethylenediamine (EDA)-modified C70 fullerene derivatives (abbreviated as FN-EDA), to break this vicious cycle. FN-EDA was successfully synthesized by modifying C70 fullerene with multiple ethylenediamine (EDA) groups, resulting in enhanced water solubility and a positive charge. This modification significantly improved ocular surface retention time, cellular uptake, and lysosomal escape in vitro. Therapeutically, FN-EDA significantly alleviated dry eye disease (DED) in a mouse model. It reduced corneal epithelial damage by 3.8-fold compared to 0.05 % cyclosporine A (CsA) and restored tear secretion to approximately 65 % of the normal level. Mechanistically, both in vivo and in vitro results demonstrate that FN-EDA is endowed with superior biological activity in effectively scavenging excessive oxidative stress, down-regulating proinflammatory cytokines expression, and promoting epithelial barrier reconstruction, even recovering corneal innervation. Thus, our findings open an avenue to make this multi-functional eye drop a promising candidate for DED.

Regeneration and repair of chronic wounds are still clinical challenges due to the imbalance of the microenvironment caused by biofilm formation by multidrug-resistant bacteria and excessive accumulation of reactive oxygen species. Here, a multifunctional OACPPIh hydrogel is developed using modified dextran (OD-AB), chitosan derivatives (CMCS-PEI), polydopamine (PDA), and iron-hydrated nanoparticles (Ih NPs). The hydrogel not only effectively combats bacterial infections and eradicates biofilms through the bacterial capture capability of OD-AB and the cationic/photothermal synergistic effects of CMCS-PEI/PDA, but also utilizes the photothermal-enhanced nanozyme activity of Ih NPs to simultaneously scavenge reactive oxygen species and generate oxygen, thereby remodeling the hypoxic microenvironment. This multi-mechanism synergistic action provides a comprehensive solution for chronic wound management. In vivo assessment conducted in a diabetic murine model achieved 94.95 % wound closure efficacy within a 15-day therapeutic regimen, with histopathological and immunofluorescence analyses corroborating its marked therapeutic potential in augmenting tissue regeneration and re-epithelialization. This integrated strategy provides a translatable solution for microenvironment-tailored chronic wound therapy materials.

Diabetic wounds heal slowly or incompletely because of the microenvironment of hyperglycemia, high levels of reactive oxygen species (ROS), excessive inflammation, metabolic disorders and immune dysregulation, and the therapeutic effect is limited only by disruption of the reactive oxygen species (ROS)-inflammation cascade cycle. Here, a novel metal-polyphenolic nanozyme (Zn-DHM NPs) synthesized by the coordination of Zn2+ with dihydromyricetin (DHM) was designed, which not only has a superior ability to scavenge ROS and promote cell proliferation and migration but also functions in the regulation of metabolism and immune homeostasis. In vitro and in vivo experiments and RNA sequencing analyses revealed that Zn-DHM NPs could increase the levels of intracellular SOD and CAT enzymes to scavenge ROS and maintain the level of the mitochondrial membrane potential to reduce apoptosis. In terms of glucose metabolism, Zn-DHM NPs downregulated excessive levels of intracellular glucose and HK2, inhibited excessive glycolysis and downregulated the AGE-RAGE pathway to restore cellular function. In terms of immune regulation, Zn-DHM NPs not only downregulate M1/M2 levels to promote tissue repair but also maintain Th17/Treg homeostasis, downregulate the IL-17 signaling pathway to reduce inflammation, and upregulate FOXP3 to maintain immune homeostasis, thereby promoting early wound healing in diabetic mice. The development of Zn-DHM NPs provides a new therapeutic target to promote early healing of diabetic wounds.

Phenalenyl chemistry has flourished for decades but currently faces bottlenecks related to synthetic challenges and stability issues. In this study, we introduced an iterative protection-oxidation-protection (POP) strategy to synthesize stabilized phenalenyl radicals (PRs) with multiple substitutions at the α-positions. The applicability of this POP strategy was verified using triisopropylsilylthyl and phenyl substituents to generate trisubstituted PR1 and hexasubstituted PR2. In particular, both oxidation and dimerization were observed during the synthesis involving phenyl substituents. Both PR1 and PR2 were bench-stable, with half-lives in solution of up to 46 d and thermal decomposition temperatures of up to 300 °C. X-ray crystallographic analysis revealed that PR1 existed as a distinct 12-center-2-electron π-dimer, whereas PR2 existed as a monomer. The properties associated with monomer-dimer equilibrium both in the solid state and in solution were systematically investigated via variable-temperature spectroscopy, and the results revealed a small singlet-triplet energy gap and concentration-dependent absorption and electrochemical behaviors. Remarkably, both PR1 and PR2 formed biocompatible nanoparticles, with the latter capable of depleting reactive oxygen species in liver cells. This study thus demonstrated the applicability of the POP strategy for the construction of stable, functionalized PR derivatives with practical applications as spin functional materials.

Wound management presents a significant clinical challenge, requiring advanced materials to support effective healing. This study reports the development of a multifunctional injectable hydrogel wound dressing (U-COC) composed of methacrylated carboxymethyl chitosan (CMCSMA), oxidized konjac glucomannan (OKGM), and (+)-catechin hydrate (CH). The formation of the U-COC hydrogel was driven by photo-initiated polymerization, dynamic reversible Schiff base bonds, and non-covalent forces (hydrogen bond interactions, π-π stacking, and hydrophobic interactions). The in vitro antioxidant and antimicrobial test results indicated that the U-COC hydrogel could effectively scavenge oxygen central free radical PTIO· (69.8 ± 0.3%) and nitrogen central free radical DPPH· (92.8 ± 0.7%), and exhibited excellent antimicrobial effects against E. coli (89.7 ± 3.9%) and S. aureus (91.4 ± 3.4%) due to the introduction of CH. Moreover, the as-designed hydrogel wound dressing was biosafe and biodegradable, demonstrating good adhesion, wound closure, self-healing properties, and shape adaptability. This hydrogel provided an advantageous microenvironment for cell proliferation, re-epithelialization, angiogenesis, collagen deposition, and tissue repair during infected wound healing. Therefore, the combination of CMCSMA, OKGM, and CH, along with the formation mechanism of the U-COC hydrogel, represents a novel advancement in wound management technology.

Due to the complexity of wound healing, the rapid promotion of wound healing has been a major unresolved challenge for the medical community. If a suitable wound dressing is not found, it can easily induce wound infection and slow down the wound repair process. Hydrogels have been recognized as the best alternative to traditional wound dressings due to their unique water-retention properties as well as their drug-carrying properties. We first outlined the entire process of wound healing, while introducing the biological activities of ten different natural polysaccharides and their mechanisms for promoting wound healing. Subsequently, we summarized the advantages and limitations of various polysaccharides in use and proposed corresponding solutions. In addition, wound dressings for a wide range of wounds, including diabetes, burns, and radiation, have also been reviewed, providing a comprehensive understanding of the applications of these hydrogels in different wound types. This paper provides an important reference for the biomedical application and clinical research of natural polysaccharide-based hydrogel in wound dressings.

The healing of deep second- and third-degree scald wounds is frequently impaired by inflammation, oxidative stress, vascular damage, and neural injury, creating substantial challenges for clinical wound management. To address this, we developed a novel hydrogel dressing strategy utilizing alpha-lipoic acid-modified chitosan (LAMC) combined with a four-armed polyethylene glycol derivative (PEG-NHS). This hydrogel achieves rapid wound coverage through its inherent adhesive properties, followed by ultraviolet (UV)-triggered secondary cross-linking to enhance mechanical stability (average compression strength reaches about 173 KPa). Concurrently, the hydrogel releases hydrogen sulfide (H₂S) gas, which exerts anti-inflammatory, antioxidant, pro-angiogenic, and neuroregenerative effects. Experimental data demonstrated that a 400 μL disulfide-containing hydrogel generated 28.89 ± 3.70 μM H₂S within 30 s of UV exposure. In vivo testing revealed a wound healing rate exceeding 95 % by day 14 in UV-treated hydrogel groups. The combination of these materials and their functional advantages provide a promising new way for the postoperative repair of severe scalded wounds.

Skin burn wounds (SBWs) are common clinical injuries due to excessive exposure to factors including heat, radiation, chemical agents, etc. However, the efficient healing of SBWs is still challenging due to persistent inflammation and high risk of local infection. To meet these challenges, we report a hydrogel-based bioactive synthetic skin (HBSS) from biocompatible components as dressing materials for burn wound treatment, which mediated localized H2S release to stimulate tissue regeneration while preventing bacterial infection and excessive inflammation. Here, the H2S donor (N-(benzoyl mercapto) benzamide) was first coassembled with thioketal (TK)-ligated dopamine dimer to form nanoscale assemblies (DDNs), which were then integrated into Schiff base-cross-linked hyaluronic acid-carboxymethyl chitosan hydrogels. The elevated acidity in burn wounds would trigger hydrogel degradation to release DDNs, which were further activated by ROS-induced cleavage of TK linkers to release H2S gas while attenuating local ROS stress in a self-immolative manner, thus promoting local angiogenesis and tissue regeneration through activating the AMPK and RAS-MAPK-AP1 prohealing pathways, while enabling M1-to-M2 macrophage reprogramming through activating the ERK1/2 and NRF2 signaling. Meanwhile, the chitosan components in the hydrogel network could inhibit bacterial colonization at the wound site to prevent local infection. These merits acted in a cooperative manner to enable accelerated and robust burn wound healing, offering an approach for burn wound treatment in the clinic.

Hydrogel wound dressings have emerged as a promising solution for wound healing due to their excellent mechanical and biochemical properties. Over recent years, there has been significant progress in expanding the variety of raw materials used for hydrogel formulation along with the development of advanced modification techniques and design approaches that enhance their performance. However, a comprehensive review encompassing diverse polymer modification strategies and design innovations for hydrogel dressings is still lacking in the literature. This review summarizes the use of natural polymers (e.g., chitosan, gelatin, sodium alginate, hyaluronic acid, and dextran) and synthetic polymers (e.g., poly(vinyl alcohol), polyethylene glycol, Pluronic F-127, poly(N-isopropylacrylamide), polyacrylamide, and polypeptides) in hydrogel wound dressings. We further explore the advantages and limitations of these polymers and discuss various modification strategies, including cationic modification, oxidative modification, double-bond modification, catechol modification, etc. The review also addresses design principles and synthesis methods, aligning polymer modifications with specific requirements in wound healing. Finally, we discuss future challenges and opportunities in the development of advanced hydrogel-based wound dressings.

Matrix metalloproteinase-9 (MMP-9) is implicated in tumor progression and vascular diseases, contributing to angiogenesis, metastasis, and extracellular matrix degradation. This review comprehensively examines the relationship between MMP-9 and these pathologies, exploring the underlying molecular mechanisms and signaling pathways involved. Specifically, we discuss the contribution of MMP-9 to tumor epithelial-mesenchymal transition, angiogenesis, and metastasis, as well as its involvement in a spectrum of vascular diseases, including macrovascular, cerebrovascular, and ocular vascular diseases. This review focuses on recent advances in MMP-9-targeted nanomedicine strategies, highlighting the design and application of responsive nanoparticles for enhanced drug delivery. These nanotherapeutic strategies leverage MMP-9 overexpression to achieve targeted drug release, improved tumor penetration, and reduced systemic toxicity. We explore various nanoparticle platforms, such as liposomes and polymer nanoparticles, and discuss their mechanisms of action, including degradation, drug release, and targeting specificity. Finally, we address the challenges posed by the heterogeneity of MMP-9 expression and their implications for personalized therapies. Ultimately, this review underscores the diagnostic and therapeutic potential of MMP-9-targeted nanomedicines against tumors and vascular diseases.

In the field of large-area trauma flap transplantation, preventing avascular necrosis remains a critical challenge. Key mechanisms for improving flap viability include angiogenesis promotion, oxidative stress inhibition, and cell death prevention. Recently, two-dimensional ultrathin Ti3C2TX (MXene) nanosheets have gained attention for their potential contributions to these processes, though MXene's physiological impact on flap survival had not been previously investigated. This study is the first to confirm MXene's biological effects on the ischaemic microenvironment post-skin flap transplantation. Findings indicated that MXene significantly decreased the necrotic area in ischaemic flaps (37.96% ± 2.00%), with reductions of 30.40% ± 1.86% at 1 mg/mL and 20.19% ± 2.11% at 2 mg/mL in a concentration-dependent manner. Mechanistically, MXene facilitated in situ angiogenesis, mitigated oxidative stress, suppressed pro-inflammatory pyroptosis, and activated the PI3K-Akt pathway, particularly influencing vascular endothelial cells. Comparative transcriptome analysis of skin tissues with and without MXene treatment provided additional evidence, highlighting mechanisms such as pro-inflammatory pyroptosis, ROS metabolic processes, endothelial cell proliferation regulation, and PI3K-Akt signaling pathway activation. Overall, MXene demonstrated biological activity, effectively promoting ischaemic flaps survival and presenting a novel strategy for addressing ischaemic necrosis in skin flaps.

Fullerene-based nanoparticles have been extensively developed and applied in biological immunotherapy due to their unique immunomodulatory properties. However, current methods for investigating their biodistribution predominantly rely on fluorescent labeling, which limits our understanding of the true biodistribution of fullerenes at both organ and suborgan levels, as well as their impact on organ-specific metabolism. In this study, we utilized laser desorption ionization and matrix-assisted laser desorption/ionization mass spectrometry imaging to achieve simultaneous in vivo mapping of fullerenes and their associated metabolites. Following tail-vein injection into mice, fullerenes were primarily localized in the liver and spleen with significant enrichment in the red pulp of the spleen. Notably, fullerene accumulation in normal tissues resulted in substantial alterations in endogenous metabolic pathways, particularly those related to pyrimidine, purine, and energy metabolism. This approach provides valuable insights into the metabolic effects of fullerenes in vivo, offering a foundation for further investigation into their biological and therapeutic implications.

Achieving scar-free skin regeneration in clinical settings presents significant challenges. Key issues such as the imbalance in macrophage phenotype transition, delayed re-epithelialization, and excessive proliferation and differentiation of fibroblasts hinder wound healing and lead to fibrotic repair. To these, we developed an active shrinkage and antioxidative hydrogel with biomimetic mechanical functions (P&G@LMs) to reshape the healing microenvironment and effectively promote skin regeneration. The hydrogel's immediate hemostatic effect initiated sequential remodeling, the active shrinkage property sealed and contracted the wound at body temperature, and the antioxidative function eliminated ROS, promoting re-epithelialization. The spatiotemporal release of LMs (ACEI) during the inflammation phase regulated macrophage polarization towards the anti-inflammatory M2 phenotype, promoting progression to the proliferation phase. However, the profibrotic niche of macrophages induced a highly contractile α-SMA positive state in myofibroblasts, whereas the sustained LMs release could regulate this niche to control fibrosis and promote the correct biomechanical orientation of collagen. Notably, the biomimetic mechanics of the hydrogel mimicked the contraction characteristics of myofibroblasts, and the skin-like elastic modulus could accommodate the skin dynamic changes and restore the mechanical integrity of wound defect, partially substituting myofibroblasts' mechanical role in tissue repair. This study presents an innovative strategy for skin regeneration.

The clinical management of radiation-induced skin injury (RSI) poses a significant challenge, primarily due to the acute damage caused by an overabundance of reactive oxygen species (ROS) and the ongoing inflammatory microenvironment. Here, we designed a dual-network hydrogel composed of 5 % (w/v) Pluronic F127 diacrylate and 2 % (w/v) hyaluronic acid methacryloyl, termed the FH hydrogel. To confer antioxidant and anti-inflammation properties to the hydrogel, we incorporated PVP-modified Prussian blue nanoparticles (PPBs) and resveratrol (Res) to form PHF@Res hydrogels. PHF@Res hydrogels not only exhibited multiple free radical scavenging activities (DPPH, ABTS), but also displayed multiple enzyme-like activities (POD-, catalase). Meanwhile, PHF@Res-2 hydrogels significantly suppressed intracellular ROS and promoted the migration of fibroblasts in a high-oxidative stress environment. Moreover, in the RSI mouse model, the PHF@Res-2 hydrogel regulated inflammatory factors and collagen deposition, significantly reduced epithelial hyperplasia, promoted limb regeneration and neovascularization, and accelerated wound healing, outperforming the commercial antiradiation formulation, Kangfuxin. The PHF@Res-2 hydrogel dressing shows great potential in accelerating wound healing in RSI, offering tremendous promise for clinical wound management and regeneration.

Wound healing is a complex and dynamic biological process that requires meticulous management to ensure optimal outcomes. Traditional wound dressings, such as gauze and bandages, although commonly used, often fall short in their frequent need for replacement, lack of real-time monitoring and absence of anti-inflammatory and antibacterial properties, which can lead to increased risk of infection and delayed healing. Here, we address these limitations by introducing an innovative hydrogel dressing, named PHDNN6, to combine wireless Bluetooth temperature monitoring and light-triggered nitric oxide (NO) release to enhance wound healing and management. The PHDNN6 hydrogel is based on a poly(N-isopropylacrylamide) (PNIPAM) matrix, integrated with methacrylated and dopamine-grafted hyaluronic acid (HA-MA-DA), which allows the dressing to be highly responsive to changes in wound temperature, enabling continuous and real-time monitoring of the wound microenvironment wirelessly. Besides, PHDNN6 is embedded with photothermal polydopamine nanoparticles (PDA NPs) that are loaded with a NO donor, N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6). When exposed to near-infrared (NIR) laser irradiation, these PDA@BNN6 nanoparticles release NO to provide potent antibacterial and anti-inflammatory effects. The integration of continuous wireless temperature monitoring with NO release within a single hydrogel dressing represents a significant advancement in clinical wound care. This dual-functional platform not only provides real-time diagnostic capabilities but also offers therapeutic interventions to manage wound infections and promote tissue regeneration. Our research highlights the potential of PHDNN6 to revolutionize wound management by offering a comprehensive solution that addresses both the diagnostic and therapeutic needs in wound healing.

Wearable temperature-sensitive electronic skin enables robots to rapidly detect environmental changes and respond intelligently, thereby reducing temperature-related mechanical failures. Additionally, this temperature-sensitive skin can measure and record the temperature of external objects, broadening its potential applications in the medical field. In this study, we designed a thermally sensitive artificial ionic skin using ionic liquids (ILs) as solvents and carbon nanotubes (CNTs) as thermally conductive fillers. The incorporation of ILs into the polymer network enhances thermal stability, while the CNTs establish dual thermal conduction pathways (CNTs-CNTs and CNTs-polymer chain segments), leading to rapid thermal response times of only 16 s. The initiation of IL dissociation at elevated temperatures boosts carrier density, resulting in a substantial improvement in thermal sensitivity (5%/°C). Furthermore, the skin displays remarkable self-healing properties (90%), thereby extending the lifespan of the skin in practical applications. This kind of skin can stably sense the wearer's body temperature and environmental temperature and provide an ideal temperature-sensitive and long-term stable new functional material for the development of human skin such as robots.

Oral ulcer wounds are difficult to heal due to bacterial infections, persistent inflammatory responses, and excessive reactive oxygen species (ROS). Therefore, the elimination of bacteria, removal of ROS, and reduction of inflammation are prerequisites for the treatment of mouth ulcer wounds. In this study, oligomeric proanthocyanidins (OPC) and 3-(aminomethyl)phenylboronic acid-modified hyaluronic acid (HP) were used to form polymer gels through dynamic covalent borate bonds. Minocycline hydrochloride (MH) was then loaded into the polymer gel, and a multifunctional MH/OPC-HP microneedles (MNs) with ROS-responsive properties was prepared using a vacuum method. The MH/OPC-HP MNs can rapidly release MH in a diffusive manner and sustainably release OPC in response to ROS. The gel-based MH/OPC-HP MNs extended the retention of OPC in oral ulcers, leading to prolonged ROS scavenging effects. Cytocompatibility and hemocompatibility tests showed that MH/OPC-HP MNs had good biocompatibility. Antibacterial experiments demonstrated that MNs loaded with MH exhibited excellent antibacterial effects. In vitro experiments indicated that MH/OPC-HP MNs could effectively clear ROS, reduce oxidative stress damage, inhibit M1-type macrophage polarization, and induce M2-type polarization. Furthermore, in vivo experiments revealed that MH/OPC-HP MNs could inhibit pro-inflammatory cytokines, promote neovascularization, accelerate epithelial healing of ulcers, and significantly promote healing in a rat model of oral ulcer wound infection. In summary, MH/OPC-HP MNs hold promise as a therapeutic strategy for enhancing the healing of oral ulcer wounds.

Inadequate vascularization significantly hampers wound recovery by limiting nutrient delivery. To address this challenge, we extracted membrane vesicles from Lactobacillus reuteri (LMVs) and identified their angiogenic potential via transcriptomic analysis. We further developed a composite hydrogel system (Gel-LMVs) by anchoring LMVs within carboxylated chitosan and cross-linking it with oxidized hyaluronic acid through a Schiff base reaction. The resulting Gel-LMVs exhibit good biocompatibility and retain the bioactivity of LMVs, which are released in a controlled manner to stimulate cell proliferation, migration, and angiogenesis in vitro by modulating gene expression in critical signaling pathways. Moreover, in an in vivo model, Gel-LMVs upregulate vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule (CD31), leading to accelerated vascularization in early healing stages, while concurrently reducing inflammation and augmenting collagen deposition to enhance wound healing quality. This approach to functionalizing biomaterials with probiotic-MVs offers an advanced strategy for wound healing.

Despite significant progress in skin wound healing, it is still a challenge to construct multifunctional bioactive dressings based on a highly aligned protein fiber coated hydrogel matrix for antifibrosis skin wound regeneration that is indistinguishable to native skin. In this study, a "dual-wheel-driven" strategy is adopted to modify the surface of methacrylated gelatin (GelMA) hydrogel with highly aligned magnetic nanocomposites-protein fiber assemblies (MPF) consisting of photothermal responsive antibacteria superparamagnetic nanocomposites-fibrinogen (Fg) complexes as the building blocks. Whole-phase healing properties of the modified hydrogel dressing, GelMA-MPF (GMPF), stem from the integration of Fg protein with RGD peptide activity decorated on the surface of the antibacterial magnetic nanoactuator, facilitating facile and reproducible dressing preparation by self-assembly and involving biochemical, morphological, and biophysical cues. Payload and substantial release of copper ions for in situ catalytic production of nitric oxide (NO) from the fiber inorganic skeleton adsorbed by Fg molecules collectively regulate the proliferation, migration, reorganization, and transdifferentiation behavior of fibroblasts and fulfill antifibrosis in the process of skin wound healing and subcutaneous appendage regeneration. In full-thickness skin lesion mouse models, the complete regeneration of skin tissue with regenerated hair follicle cells and capillary blood vessels is realized in a temporally and spatially ordered manner.

Diabetic wounds are increasingly common and challenging to treat due to high infection risks in a high-glucose environment. Effective treatment requires wound dressings that combat infections, while promoting angiogenesis and skin regeneration. This study presents a hydrogel-based drug delivery system made from cellulose designed to accelerate diabetic wound healing by eliminating bacterial infections. The hydrogel, formed by linking phenylboronic acid-grafted oxidized methylcellulose (POMC) with poly(vinyl alcohol) (PVA), exhibits self-healing and injectable properties. It is further enhanced by adding type I recombinant human collagen (rhCOL1) to stimulate cell growth and angiogenesis and mesoporous zinc oxide (mZnO) for antibacterial and anti-inflammatory effects. Upon application, the hydrogel degrades under pH/ROS stimuli, releasing mZnO and rhCOL1 in a controlled manner that matches the wound healing stages. In vivo tests show that the hydrogel effectively eliminates bacteria, reduces inflammation, and promotes rapid skin regeneration, making it a promising solution for treating diabetic wounds.

Hydrogel bioadhesives have emerged as a promising alternative to wound dressings for chronic wound management. However, many existing bioadhesives do not meet the functional requirements for efficient wound management through dynamically mechanical modulation, due to the reduced wound contractibility, frequent wound recurrence, incapability to actively adapt to external microenvironment variation, especially for those gradually-expanded chronic wounds. Here, a self-growing hydrogel bioadhesive (sGHB) patch that exhibits instant adhesion to biological tissues but also a gradual increase in mechanical strength and interfacial adhesive strength within a 120-h application is presented. The gradually increased mechanics of the sGHB patch could effectively mitigate the stress concentration at the wound edge, and also resist the wound expansion at various stages, thus mechanically contracting the chronic wounds in a programmable manner. The self-growing hydrogel patch demonstrated enhanced wound healing efficacy in a mouse diabetic wound model, by regulating the inflammatory response, promoting the faster re-epithelialization and angiogenesis through mechanical modulation. Such kind of self-growing hydrogel bioadhesives have potential clinical utility for a variety of wound management where dynamic mechanical modulation is indispensable.

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements and the potential of hydrogels in therapeutic applications, focusing primarily on two areas: emerging cell-based therapies and promising non-cell therapeutic modalities. Within the context of cell therapy, we discuss the capacity of hydrogels to overcome the existing translational challenges faced by mainstream cell therapy paradigms, provide a detailed discussion on the advantages and principal design considerations of hydrogels for boosting the efficacy of cell therapy, as well as list specific examples of their applications in different disease scenarios. We then explore the potential of hydrogels in drug delivery, physical intervention therapies, and other non-cell therapeutic areas (e.g., bioadhesives, artificial tissues, and biosensors), emphasizing their utility beyond mere delivery vehicles. Additionally, we complement our discussion on the latest progress and challenges in the clinical application of hydrogels and outline future research directions, particularly in terms of integration with advanced biomanufacturing technologies. This review aims to present a comprehensive view and critical insights into the design and selection of hydrogels for both cell therapy and non-cell therapies, tailored to meet the therapeutic requirements of diverse diseases and situations.

One primary focus of skin tissue engineering has been the creation of innovative biomaterials to facilitate rapid wound healing. Extracellular matrix (ECM), an essential biofunctional substance, has recently been discovered to play a crucial role in wound healing. Consequently, we endeavored to decellularize ECM from pig achilles tendon and refine its mechanical and biological properties through modification by utilizing cross-linking agents. Glutaraldehyde (GA), 1-ethyl-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), double aldol starch (DAS), and microbial transglutaminase (MTG) were utilized to produce crosslinked ECM variants (GA-ECM, EDC/NHS-ECM, DAS-ECM, and MTG-ECM). Comprehensive assessments were conducted to evaluate the physical properties, biocompatibility, and wound healing efficacy of each material. The results indicated that MTG-ECM exhibited superior tensile strength, excellent hydrophilicity, minimal cytotoxicity, and the best pro-healing impact among the four modified scaffolds. Staining analysis of tissue sections further revealed that MTG-ECM impeded the transition from type III collagen to type I collagen in the wound area, potentially reducing the development of wound scar. Therefore, MTG-ECM is expected to be a potential pro-skin repair scaffold material to prevent scar formation.

Electrospun nanofiber membranes hold great promise as scaffolds for tissue reconstruction, mirroring the natural extracellular matrix (ECM) in their structure. However, their limited bioactive functions have hindered their effectiveness in fostering wound healing. Inorganic nanoparticles possess commendable biocompatibility, which can expedite wound healing; nevertheless, deploying them in the particle form presents challenges associated with removal or collection. To capitalize on the strengths of both components, electrospun organic/inorganic hybrid nanofibers (HNFs) have emerged as a groundbreaking solution for accelerating wound healing and maintaining stability throughout the healing process. In this review, we provide an overview of recent advancements in the utilization of HNFs for wound treatment. The review begins by elucidating various fabrication methods for hybrid nanofibers, encompassing direct electrospinning, coaxial electrospinning, and electrospinning with subsequent loading. These techniques facilitate the construction of micro-nano structures and the controlled release of inorganic ions. Subsequently, we delve into the manifold applications of HNFs in promoting the wound regeneration process. These applications encompass hemostasis, antibacterial properties, anti-inflammatory effects, stimulation of cell proliferation, and facilitation of angiogenesis. Finally, we offer insights into the prospective trends in the utilization of hybrid nanofiber-based wound dressings, charting the path forward in this dynamic field of research.