Conventional drug-eluting balloons and stents continue to be associated with risks of in-stent restenosis and late-stage thrombosis, which may be attributed to severe endothelial injury during implantation and delayed re-endothelialization caused by early excessive release of anti-proliferative agents. Therefore, developing stent coatings that promote rapid endothelialization represents a promising strategy to reduce the risk of restenosis. Capitalizing on the distinctive features of the atherosclerotic microenvironment—particularly elevated reactive oxygen species (ROS) and acidic pH—we engineered a cascade drug-release coating by crosslinking oxidized sodium alginate with cystamine and incorporating atorvastatin (ATO)-loaded Cu-based layered double hydroxide (CuLDH*). This system operates through a sequential release mechanism: ROS-triggered degradation of the coating liberates CuLDH*, which subsequently decomposes under acidic conditions to release ATO and Cu2+ ions. The released Cu2+ further acts as a catalyst for generating nitric oxide (NO) from endogenous donors. This cascade strategy effectively circumvents the risk of cytotoxic peroxynitrite formation associated with direct NO donor application in high-ROS settings, while the pH-responsive CuLDH carrier prevents premature burst release of ATO, ensuring sustained and controlled drug elution. Therapeutically, the released Cu2+ ions catalyze the generation of NO from endogenous donors (e.g., S-nitrosothiols), while ATO and endogenously produced NO act synergistically to promote endothelial cell proliferation, migration, and functional restoration. This cascade drug-release coating enables the precise delivery of ATO and Cu2+ to cooperatively enhance endogenous NO bioavailability. This work provides a novel strategy for stent coating design, featuring a smart design that enables rapid re-endothelialization through programmed drug release.

Establishing a durable soft tissue seal around dental implants is critical for preventing peri-implantitis, yet efficient loading of exosomes onto titanium surfaces remains challenging. Here, a dual-functional coating was developed on anodized porous titanium combining stem cell-derived exosomes with cefotaxime sodium via a chemo-physical loading strategy. Porous titanium surfaces exhibited 27% of pores equal/larger than 150 nm at 150 V along with enhanced hydrophilicity. Exosomes loaded via chemo-physical approach achieved the highest loading (30.8 μg/cm2), 2.6-fold higher than chemical grafting alone, while preserving bioactivity. In vitro, porous titanium and exosome-modified surfaces promoted epithelial cell adhesion and induced spindle-shaped fibroblast morphology. In vivo subcutaneous implantation demonstrated good biocompatibility across all groups, as evidenced by absence of necrosis or abscess, and comparable fibrous capsule thickness (~150 μm). No adverse tissue reactions were observed for any of the tested surfaces. These findings demonstrate that chemo-physical loading on optimized porous titanium enables stable, high-capacity exosome immobilization. The resulting dual-functional coating simultaneously promotes soft tissue cell responses and provides antibacterial protection, offering a promising strategy for supporting the tissue healing around dental implants.

Stainless steel bipolar plates (BPs) for proton exchange membrane fuel cells (PEMFC) face an inherent corrosionconductivity conflict. Corrosion-resistant passivation layers, such as Cr2O3, induce unacceptable interfacial contact resistance (ICR) elevation. We resolve this conflict using high-power impulse magnetron sputtering (HiPIMS) to deposit FeCoNiCrCx coatings with carbon-mediated defect control, where acetylene flow regulation (0-5 sccm) triggers three synergistic effects: carbon-mediated amorphization eliminates grain boundaries to suppress ionic diffusion; in-situ carbide formation, primarily Cr3C2, consumes reactive metals and inhibits oxide nucleation; and sp2-carbon networks establish efficient electron-conduction pathways. The optimized 5 sccm coating delivers exceptional performance in simulated PEMFC cathode conditions: corrosion current plunges to 0.079 mu A/cm2. Simultaneously, ICR is maintained at 7.9 m Omega cm2 under 1.4 MPa compaction, outperforming U.S. Department of Energy (DOE) 2025 targets. X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) analyses validate a carbon-dominated barrier layer exceeding 80 at.% carbides and amorphous carbon. This layer effectively replaces insulating oxides, ensuring post-polarization ICR stability. This work demonstrates conductive passivation as an effective materials strategy that breaks the persistent corrosionconductivity trade-off in metallic BPs through carbon-mediated defect control.

Abstract Nanozymes including noble metals, metal oxides, metal‐organic frameworks, carbon‐based nanomaterials, and layered double hydroxides (LDHs) have undergone rapid development in recent years. In addition to the cost‐effectiveness, high stability, and superior catalytic capabilities of common nanozymes, LDHs have unique characteristics such as extensive surface area, anion exchange capacity, adjustable composition/structure, and low toxicity. Leveraging these properties, LDH‐based nanozymes (LDHzymes) with enzyme‐like activity demonstrate significant potential for applications, particularly in biomedicine. This review summarizes the preparation methods for LDHzymes with different morphology and elucidates their catalytic activities (including peroxidase‐, oxidase‐, superoxide dismutase‐, and catalase‐like activity) and mechanisms. Subsequently, the applications of LDHzymes across biomedical fields are examined, including biosensing and detection, antimicrobial properties, treatment of tumors, and reactive oxygen species‐related diseases. Finally, future research directions for LDHzymes are proposed, including the design of high‐performance LDHzymes, intelligent therapeutic applications, and the expansion of application fields, which provide a framework for the development of novel LDHzymes for biomedical applications.

Copper ions have demonstrated significant potential in vascular applications due to their pro-regenerative and antimicrobial properties. Yet, the current research remains fragmented, with a conspicuous absence of a holistic, systems-level understanding of how copper ions concurrently orchestrate the responses of all key cellular players in the vascular niche. This study systematically mapped the dose-response relationships of copper ions across five key vascular cell types (endothelial cells, smooth muscle cells, macrophages, mesenchymal stem cells, and fibroblasts), identifying a core therapeutic window (5-20 μM). This window uniquely promotes endothelial and stem cell activity while maintaining smooth muscle cell quiescence and modulating macrophage viability. Beyond concentration, the timing of copper delivery (post-attachment addition being superior to co-culture seeding) and the presence of cell-cell interactions (e.g., endothelial-stem cell crosstalk) were also identified as critical determinants of the pro-regenerative outcome. Guided by the therapeutic window, a copper-modified implant was engineered and evaluated in vivo. This implant significantly reduced neointimal thickness, enhanced endothelial coverage, and mitigated inflammation. These in vivo results validated the in vitro mechanisms, and the systems-level understanding of multicellular responses will provide a guideline for the rational design of implants that orchestrate harmonious tissue repair.

Conventional drug-eluting stents can lead to complications such as in-stent restenosis and late thrombosis due to the lack of a well-functioning endothelium and inadequate inflammatory regulation. In this study, a dual exosome coating was fabricated to promote endothelial function and macrophage efferocytosis via a synergistic effect by endothelial cell-sourced and mesenchymal stem cell-sourced exosomes. By the biotin-avidin interaction, the dual exosomes were proportionally grafted onto the substrate and evenly distributed. The coating facilitated the formation of a functionally intact endothelial layer, inhibited macrophage adhesion, and suppressed inflammation. The dual exosomes on the coating acted through upregulating the expression of eNOS and downregulating NOX1 and NOX4 to reduce oxidative stress and effectively repair endothelial function. The dual exosomes also upregulated the expression of SLC29a1 and SLC2a1 and downregulated CD300a, CD36, and Lp-PLA2 to promote efferocytosis and inhibit inflammation. Additionally, it promoted smooth muscle cell phenotypic transformation, reduced thrombosis, and decreased the neointima thickness. Overall, this coating loaded with dual exosomes provided a potential and universal strategy for vascular stent surface modification.

Vascular stents are frequently used in interventional therapy for atherosclerotic arteries. Interventional treatment with bare metal stents and drug-eluting stents has significantly reduced mortality. Restenosis and late thrombus were also major safety concerns in stent implantation. Hyaluronic acid (HA), a multifunctional polymer, is commonly used for surface modification of biomaterials. However, its application in vascular stents still faces challenges, as it is susceptible to degradation by reactive oxygen species (ROS) and hyaluronidase (HAase), leading to the formation of pro-inflammatory small molecular fragments that can affect the stability and functionality of vascular stent coatings. Based on controllable oxidative stress, we propose and construct a multifunctional molecular composite coating using baicalin (BCL), achieving successful synergy between BCL and HA. The surface-fixed BCL in the coating resists ROS and HAase to prevent surface HA degradation, reducing macrophage transition to pro-inflammatory phenotypes and smooth muscle cell transition to synthetic phenotypes. Additionally, it protects endothelial cells in oxidative stress environments, promotes endothelialization, and reduces HAase expression levels in tissues to enhance tissue stability. Therefore, this study presents a promising biomedical surface modification method for vascular stents.

Endothelial cell-sourced exosomes are potential participants in the process of atherosclerosis, and their function is mainly affected by concentration. By studying the effects of exosome concentrations on vascular cells, atherosclerosis can be better intervened. In this study, exosomes with concentrations of 0, 0.07, 0.35, 1.75 and 8.75 mu g/mL were set to interact with endothelial cells, macrophages and smooth muscle cells respectively. The results suggested that EC-Exo altered vascular cells' proliferation, migration and nitric oxide release abilities, increasing with EC-Exo concentrate from 0 to 1.75 mu g/mL and varing with cell types at 8.75 mu g/mL. The effects of exosome on cells is dose-responsive,and endothelial cells-sourced exosome favors vascular repair within the concentration of 0.35-1.75 mu g/mL,showing potential for atherosclerosis regulation.

Carotid atherosclerosis is an essential cause of transient cerebral ischemia, stroke, and other cerebrovascular diseases, and carotid endarterectomy (CEA) is currently the most effective treatment for removing plaque and restoring the vascular lumen. However, the CEA disrupts the integrity and functionality of the endothelium and predisposes it to complications such as restenosis and thrombosis. Hydrogels can closely mimic the natural extracellular matrix, allowing a wide tuning of physical and chemical properties. These properties make hydrogels the most promising candidate materials for the repair of vascular injured intima. In this study, a multifunctional intimal repair hydrogel of poly(ethylene glycol)-norbornene (PEGNB)/ Heparin/ Liposome is proposed with the advantages of ultra-rapid adhesion to the wet tissue of the vascular inner wall, maintenance of adhesion stability under continuous erosion by blood flow. The hydrogel was supplemented with poly(vinyl butyral) (PVB) to reduce its swelling rate, and Rapamycin (RAPA) was encapsulated in this study as the drug into the cationic liposomes. This composite multifunctional (PNHB@Lip(RAPA)) hydrogel has exhibited outstanding anti-coagulation properties, markedly suppressed the proliferation and migration of SMCs, and displayed favourable cytocompatibility and blood compatibility. Concurrently, the capacity of the PNHB@Lip(RAPA) hydrogel to stimulate endovascular regeneration and deter restenosis and thrombus formation was validated through carotid intima damage repair experiments. These findings collectively indicate that the PNHB@Lip(RAPA) hydrogel represents a promising material for intimal injury repair, offering innovative insights into intimal repair methodologies. STATEMENT OF SIGNIFICANCE: Carotid atherosclerosis is a leading cause of transient cerebral ischemia, stroke, and cerebrovascular disorders. Although carotid endarterectomy (CEA) effectively removes plaques, it damages endothelial integrity, increasing the risk of restenosis and thrombosis. To address this, we developed PNHB@Lip(RAPA), a multifunctional intimal repair hydrogel composed of PEGNB, heparin, and rapamycin-encapsulated liposomes. This hydrogel rapidly adheres to wet vascular walls, resists blood flow erosion, and exhibits low swelling. The hydrogel demonstrates superior anticoagulation, inhibits smooth muscle cell proliferation and migration, and shows favourable cytocompatibility. Experimental results confirm its ability to promote endovascular regeneration while preventing restenosis and thrombosis. In summary, PNHB@Lip(RAPA) hydrogel is a promising material for intimal repair, offering innovative solutions to improve CEA postoperative outcomes.

IntroductionTitanium dioxide (TiO2) films have been widely studied as blood-contacting materials, but their positively charged surface and low density of surface hydroxyl (-OH) groups result in poor intrinsic anticoagulant properties. Furthermore, TiO2 surfaces readily adsorb carbon-containing contaminants from the environment, causing a rapid decline in anticoagulant performance during storage. Thus, improving TiO2's intrinsic anticoagulant properties and extending its shelf-life remain challenging.MethodsWe fabricated a bilayer film by depositing a ∼40 nm silica (SiO2) overlayer onto TiO2 using unbalanced magnetron sputtering. Surface properties (hydrophilicity, surface charge, and contaminant adsorption) and anticoagulant performance (platelet adhesion after storage) of the resulting SiO2/TiO2 bilayer were characterized.ResultsThe SiO2/TiO2 bilayer exhibited long-lasting hydrophilicity, a net negative surface charge, minimal adsorption of carbonaceous contaminants, and a high surface -OH group content. These characteristics are attributed to the formation of interfacial Si–O–Ti bonds, which in turn led to significantly enhanced anticoagulant properties. Notably, after 15 weeks of storage, platelet surface coverage on the bilayer was less than 30% of that on a TiO2-only film, indicating greatly improved long-term hemocompatibility.DiscussionBy maintaining a hydrophilic, clean surface with abundant surface -OH groups, the SiO2/TiO2 bilayer achieved superior intrinsic anticoagulant performance that was preserved over long-term storage. This bilayer approach addresses key limitations of TiO2, suggesting that SiO2/TiO2 coatings are a promising alternative to pure TiO2 films for blood-contacting devices.

The effective measure to promoting endothelial repair is to construct a surface similar to that of normal vascular on blood contact materials. The construction of cell culture platform regulating platelets, endothelial cells (ECs) and Smooth muscle cells (SMCs) may provide more help to promote endothelial repair. In this work, a novel versatile cell research platform UV-P-PDA@TiO2 was constructed by magnetron sputtering and photoetching. The surface of UV-P-PDA@TiO2 was evaluated by materials science methods such as FTIR, Raman, Micro BCA and WCA, and cell culture was performed on the surface. These results indicated that UV-P-PDA@TiO2 platform regulated the cellular behavior of platelets, ECs, and SMCs, achieved selective adhesion, and exhibited orientation. The advantage of histocompatibility was demonstrated by in vivo tests that UV-P-PDA@TiO2 had pattern stability and inhibited tissue proliferation. Conceivably, the regulating the multicellular UV-P-PDA @ TiO2 culture platform may provide a versatile surface engineering strategy for biomaterials.

Diabetic wound treatment continues to be a significant clinical issue due to higher levels of oxidative stress, susceptibility to bacterial infections, and chronic inflammatory responses during healing. We rationally developed and synthesized an ultra-small carbon dots (C-dots) loaded with zinc single-atom nanozyme (Zn/C-dots) with the aim of promoting wounds healing by nanocatalytic treatment, especially targeting its complex pathological microenvironment. Zinc single atoms and C-dots form a dual catalytic system with higher enzymatic activity. Furthermore, the Zn/C-dots nanozyme effectively enters cells, accumulates at mitochondria, and removes excess ROS, protecting cells from oxidative stress damage and limiting the release of pro-inflammatory cytokines, hence reducing inflammation. Zinc can synergistically increase the antibacterial action of C-dots (the effective antibacterial rate of 100 µg/mL Zn/C-dots was above 90 %). Unlike traditional C-dots, Zn/C-dots can cause endothelial cell migration and the formation of new blood vessels. In vitro cytotoxicity, blood compatibility, and in vivo toxicity studies of Zn/C-dots show that they are biocompatible. We subsequently utilized the Zn/C-dots nanozymes to treat diabetic rats' chronic wounds for external use, combining them with ROS-responsive hydrogels to create an antioxidative system (H-Zn/C-dots). The hydrogels anchored the Zn/C-dots nanozymes to the wound, allowing for long-term treatment. The results revealed that H-Zn/C-dots can considerably reduce inflammation, accelerate angiogenesis, collagen deposition, and promote tissue remodeling at the diabetic wound site. After 14 days, the wound area had decreased to approximately 9.19 %, making it a potential treatment. Statement of significance An ultra-small carbon dot with a zinc single-atom nanozyme was designed and manufactured. Zn/C-dots possess antibacterial, ROS-scavenging, and angiogenesis activities. In vivo, the multifunctional ROS-responsive hydrogel incorporating Zn/C-dots could speed up diabetic wound healing.

Bio-absorbable magnesium (Mg) alloys exhibit significant promise for implantable medical devices, particularly in orthopedic applications. However, their limited corrosion resistance and rapid degradation rates have hindered their clinical translation. To address this long-standing challenge, here we developed a composite coating system (PTMC-MAO) for Mg-alloys, seamlessly integrating Microarc oxidation (MAO) and Poly-(Trimethylene Carbonate) (PTMC) layers. Leveraging the synergistic effects between MAO coatings, generated through micro-arc oxidation, and PTMC coatings, synthesized via gradual dropwise addition, our approach effectively controls corrosion and degradation rates of a widely applied Mg-alloy (AZ31) both in terms of kinetics and thermodynamics. Compared with the uncoated AZ31, the PTMC-MAO coatings exhibited greater positive Ecorr of -1290 mV and lower icorr of 5.3nA· cm-2 with a significant 851-fold reduction. The coatings reached up to a distinguished protection efficiency (η) of 99.9%, accompanying with the higher impedance |Z| of 4×105 Ω·cm2. The ΔpH change and the released Mg2+ concentration were 0.25 and 42μg/ml, respectively, after 21 days of immersion. Both values were superior to those observed for the AZ31 substrate. These results highlight the transformational potential of PTMC-MAO composite coatings, indicating their feasibility as a new class of materials for engineering the surfaces of Mg-based degradable implants.

The utilization of nanomaterials in disease treatment has become a prominent area of research in the medical field. Nanocarrier materials endowed with catalytic and biological enzyme properties have exhibited promising prospects for applications in treating chronic inflammatory diseases, including cancer and diabetes. In this study, we have successfully synthesized a versatile CuTA nanosheets with a cost-effective approach, making it suitable for various pathological models. The CuTA nanosheets exhibit remarkable characteristics, including catalyzing the Fenton reaction for peroxide decomposition and accelerating the release of nitric oxide (NO) through the catalysis of endothelial nitric oxide synthase (eNOS), both of which are dependent on the concentration of the CuTA nanosheets. Furthermore, at a concentration of 2 mg/mL, the CuTA nanosheets achieved a removal rate of free radicals at 63.7%. When exposed to 808 nm near-infrared light, the temperature rose from 8 C to 42 C within 10 min. Additionally, at a concentration of 50 mu g/mL, the inhibition rates of CuTA nanosheets on Escherichia coli and Staphylococcus aureus reached 98.3% and 96.1%, respectively. These unique characteristics make it highly suitable for effective applications in various fields, including biomedical, drug delivery, and photothermal therapy.

Cardiovascular disease poses a significant threat to human health in today's society. A major contributor to cardiovascular disease is atherosclerosis (AS). The development of plaque in the affected areas involves a complex pathological environment, and the disease progresses rapidly. Nanotechnology, combined with emerging diagnostic and treatment methods, offers the potential for the management of this condition. This paper presents the latest advancements in environment-intelligent responsive controlled-release nanoparticles designed specifically for the pathological environment of AS, which includes characteristics such as low pH, high reactive oxygen species levels, high shear stress, and multienzymes. Additionally, the paper summarizes the applications and features of nanotechnology in interventional therapy for AS, including percutaneous transluminal coronary angioplasty and drug-eluting stents. Furthermore, the application of nanotechnology in the diagnosis of AS shows promising real-time, accurate, and continuous effects. Lastly, the paper explores the future prospects of nanotechnology, highlighting the tremendous potential in the diagnosis and treatment of atherosclerotic diseases, especially with the ongoing development in nano gas, quantum dots, and Metal-Organic Frameworks materials.

Poor wound healing in diabetics is primarily caused by persistently high levels of inflammation and recurrent bacterial infections. The catalytic therapy technique based on nanozyme medicine has emerged as a beacon of hope for patients with diabetic wounds. However, the use of a single-atom nanozyme may still have limitations, including nanozyme burst release, immunological clearance and insufficient antibacterial activity. To address the aforementioned problems, we provide a new nano-catalytic therapeutic agent for diabetic skin ulcers that incorporates a single-atom nanozyme with high antioxidant activity into a metal-organic framework (ZIF-Cu/C-dots). First, a Cu single-atom nanozyme supported by ultra-small carbon dots (Cu/C-dots) with high antioxidant activity was created. A nanozyme-integrated metal-organic framework was then created, utilizing Cu/C-dots as ligands and Zn2+ as the core metal. Cu/C-dots have good oxidase-like activity, shielding the biological system from ROS damage and reducing the expression of TNF-α and IL-1β. Zn2+ also has good antibacterial activity (the antibacterial rate was more than 90%). This integrated technique prevents nanozyme aggregation, improves nanozyme biocompatibility, slows down the breakdown of ZIF and allows for the regulated release of Cu/C-dots and Zn2+ as needed. Finally, in vivo studies have shown that ZIF-Cu/C-dots can effectively alleviate inflammation at the site of diabetic wounds, accelerate vascular regeneration, promote collagen deposition and enhance tissue remodeling, serving as a novel nano-catalytic platform for the treatment of wounds that are difficult to heal.

Efferocytosis, responsible for apoptotic cell clearance, is an essential factor against atherosclerosis. It is reported that efferocytosis is severely impaired in fibroatheroma, especially in vulnerable thin cap fibroatheroma. However, there is a shortage of studies on efferocytosis defects in cell and animal models. Here, the impacts of oxidized low density lipoprotein (ox-LDL) and glut 1 inhibitor (STF31) on efferocytosis of macrophages are studied, and an evaluation system is constructed. Through regulating the cell ratios and stimulus, three types of atherosclerotic spheroids are fabricated, and a necrotic core emerges with surrounding apoptotic cells. Rat models present a similar phenomenon in that substantial apoptotic cells are uncleared in time in vulnerable plaque, and the model period is shortened to 7 weeks. Mechanism studies reveal that ox-LDL, through mRNA and miRNA modulation, downregulates efferocytosis receptor (PPARγ/LXRα/MerTK), internalization molecule (SLC29a1), and upregulates the competitive receptor CD300a that inhibits efferocytosis receptor-ligand binding process. The foam cell differentiation has also confirmed that CD36 and Lp-PLA2 levels are significantly elevated, and macrophages present an interesting transition into prothrombic phenotype. Collectively, the atherosclerotic models featured by efferocytosis defect provide a comprehensive platform to evaluate the efficacy of medicine and biomaterials for atherosclerosis treatment.

Corneal injury inevitably leads to disruption of the ocular surface microenvironment, which is closely associated with delayed epithelial cell repair and the development of infection. Recently, drug-loaded therapeutic contact lenses have emerged as a new approach to treating corneal injury due to their advantages of relieving pain, promoting corneal repair, and preventing infection. However, few therapeutic contact lenses could modulate the ocular surface's inflammation and oxidative stress microenvironment. To address this, in this study, we covalently immobilized multifunctional baicalin (BCL), a flavon molecular with anti-inflammatory, anti-oxidative stress, and antibacterial capabilities, onto the surface of the contact lens. The BCL-modified contact lens showed excellent optical properties, powerful antibacterial properties, and non-toxicity to endothelial cells. Furthermore, the BCL-modified contact lens could significantly modulate the ocular surface microenvironment, including inhibition of macrophage aggregation and resistance to epithelium damage caused by oxidative stress. In animal models, BCL-modified corneal contact lens effectively promoted corneal epithelial cells repair. These excellent properties suggested that multifunctional BCL molecules had great application potential in the surface engineering of ophthalmic medical materials.

Chronic wounds and the accompanying inflammation are ongoing challenges in clinical treatment. They are usually accompanied by low pH and high oxidative stress environments, limiting cell growth and proliferation. Ordinary medical gauze has limited therapeutic effects on chronic wounds, and there is active research to develop new wound dressings. The chitosan hydrogel could be widely used in biomedical science with great biocompatibility, but the low mechanical properties limit its development. This work uses polyacrylamide to prepare double-network (DN) hydrogels based on bioadhesive catechol-chitosan hydrogels. Cystamine and N, N′-Bis(acryloyl)cystamine, which can be cross-linking agents with disulfide bonds to prepare redox-responsive DN hydrogels and pH-responsive nanoparticles (NPs) prepared by acetalized cyclodextrin (ACD) are used to intelligently release drugs against chronic inflammation microenvironments. The addition of catechol groups and ACD-NPs loaded with the Resolvin E1 (RvE1), promotes cell adhesion and regulates the inflammatory response at the wound site. The preparation of the DN hydrogel in this study can be used to treat and regulate the inflammatory microenvironment of chronic wounds accurately. It provides new ideas for using inflammation resolving factor loaded in DN hydrogel of good biocompatibility with enhanced mechanical properties to intelligent regulate the wound inflammation and promote the wound repaired.