目的·构建一种基于透明质酸（hyaluronic acid，HA）的自愈合可注射性水凝胶，探究不同浓度铜离子对水凝胶性能及其促成血管功效的影响，评估其应用于临床上伤口愈合的可行性。方法·在光引发剂2959的存在下，通过蓝光诱发了巯基化透明质酸（thiolated hyaluronic acid，HASH）和丙烯酸化双膦酸盐（acrylated bisphosphonate，Ac-PD）之间的巯基-烯点击反应，制备了双膦酸盐化透明质酸（bisphosphonated hyaluronic acid，HAPD）；基于HAPD和Cu²⁺的金属配位作用，构建了不同Cu²⁺浓度的HAPD-Cu水凝胶，即HAPD-Cu1、HAPD-Cu2、HAPD-Cu3以及HAPD-Cu4。采用核磁氢谱以及傅里叶红外光谱验证HASH、Ac-PD、HAPD和HAPD-Cu的分子结构；采用扫描电镜观察HAPD-Cu的微观形貌；采用流变仪验证HAPD-Cu的剪切变稀和自修复特性；采用液相质谱仪测定HAPD-Cu的离子释放；通过活/死细胞染色和CCK-8评价HAPD-Cu的生物相容性；通过人脐静脉血管内皮细胞的成小管实验测定HAPD-Cu的体外促成血管活性；通过CD31组织染色评估HAPD-Cu的体内促成血管活性并建立体外大鼠伤口缺陷模型评价其实际修复效果。结果·化学定性和定量分析手段证明材料的成功制备；体外研究表明，HAPD-Cu均具有疏松多孔的内部结构，且具有优异的自愈性、可注射性和可降解性，降解周期为7d并具有突释行为，满足伤口愈合周期的需求；HAPD-Cu具有良好的生物相容性，但HAPD-Cu4因Cu²⁺浓度高而具有细胞毒性。此外，在允许的Cu²⁺浓度范围内，其体外或体内的成血管效果随着Cu²⁺浓度的增加而增强；且体外伤口模型实验表明，与对照组相比，HAPD-Cu水凝胶显著促进了伤口的愈合。结论·基于金属配位制备的HAPD-Cu水凝胶具有优异的形状可塑性，允许以微创的形式填充缺陷部位，并释放Cu²⁺以促进早期血管网络的建立，在用于临床上不规则的伤口修复方面具有良好的应用潜力。

Objective ·To construct a self-healing injectable hyaluronic acid (HA)-based hydrogel (HAPD-Cu) and investigate the effects of different copper ions on the properties of the hydrogel and its vasogenic efficacy to evaluate its feasibility for clinical wound healing. Methods ·Bisphosphonated hyaluronic acid (HAPD) was prepared via a blue-light mediated thiol-ene click reaction between thiolated hyaluronic acid (HASH) and acrylated bisphosphonate (Ac-PD) in the presence of photoinitiator 2959. Then, HAPD was further interacted with Cu²⁺ through metal coordination to prepare HAPD-Cu hydrogels with different Cu²⁺ concentrations, i.e. HAPD-Cu1, HAPD-Cu2, HAPD-Cu3 and HAPD-Cu4. The molecular structures of HASH, Ac-PD, HAPD and HAPD-Cu were verified with ¹HNMR and FTIR. Microscopic morphology of HAPD-Cu was observed under SEM. The shear-thinning and self-healing properties of HAPD-Cu were verified by rheometer. The Cu²⁺ release from HAPD-Cu was determined with ICP. Live-dead staining and CCK-8 assay were applied to evaluate the biocompatibility of HAPD-Cu. The in vitro vasculogenic activity of HAPD-Cu was determinedby a tubule-forming assay with human umbilical vein vascular endothelial cells and the in vivo vasculogenic activity of HAPD-Cu was assessed by CD31 tissue staining. A rat wound defect model was established in vitro to evaluate its actual repair effect. Results ·The preparation of the materials was demonstrated through chemical qualitative and quantitative analytical means. In vitro studies showed that all HAPD-Cu with a loose porous internal structure exhibited outstanding self-healing, injectability and degradability, with a one-week degradation cycle and abrupt release behavior, which can meet the needs of wound healing cycle. All HAPD-Cu showed good biocompatibility except HAPD-Cu4, due to its high Cu²⁺ concentrations. Moreover, its angiogenic effect in vitro or in vivo was enhanced with increasing Cu²⁺ concentrations within the permissible Cu²⁺ concentration range. In vitro wound model experiments also showed that the HAPD-Cu hydrogel significantly promoted wound healing compared with the control group. Conclusion ·HAPD-Cu hydrogel constructed via the metal coordination shows excellent shape plasticity, allowing the filling of defective sites in a minimally invasive form, and the release of Cu²⁺ greatly facilitates the establishment of early vascular networks, with giant potential for use in the repair of clinically irregular wounds.