智能响应水凝胶在糖尿病伤口修复中的研究进展

Research Progress on Advanced Responsive Hydrogels for Diabetic Wound Healing

摘要: 糖尿病伤口因其复杂的病理微环境(如高血糖、异常pH波动、活性氧过载及基质金属蛋白酶过表达等)而难以愈合，传统敷料因药物释放模式单一难以实现精准治疗。水凝胶作为一种新兴的伤口敷料，在治疗不规则创面时具有其独特优势。而近年来，智能响应水凝胶通过动态调控药物释放机制，在糖尿病伤口治疗中展现出显著优势。目前水凝胶的响应主要通过内源环境响应与外源刺激两种形式。内源环境响应的药物控释水凝胶可响应糖尿病伤口的环境变化，达到药物按需释放的效果：高血糖响应水凝胶、pH敏感水凝胶、活性氧响应、基质金属蛋白酶响应水凝胶感知糖尿病伤口的微环境变化，动态释放抗炎、抗菌药物以促进伤口进入正常愈合流程。此外，外源性物理刺激(如电场和超声)通过调控凝胶溶胀、电泳迁移或结构崩解增强药物渗透与控释能力。这些多模态药物释放系统通过时空匹配创面微环境动态变化，协同调控炎症、抗菌、血管生成和组织重塑等关键环节，显著提升药物生物利用度并规避耐药风险，有望推动智能敷料的临床转化。

Abstract: Diabetic wounds are difficult to heal due to their complex pathological microenvironment (e.g., hyperglycemia, abnormal pH fluctuations, reactive oxygen species overload, and overexpression of matrix metalloproteinases). Conventional dressings, which rely on a single drug release mode, are inadequate for achieving precision therapy. Hydrogels, as an emerging class of wound dressings, offer unique advantages in treating irregular wounds. In recent years, smart responsive hydrogels have demonstrated significant advantages in diabetic wound therapy by dynamically modulating drug release mechanisms. Currently, the responsiveness of hydrogels is primarily achieved through two forms: endogenous environmental responses and exogenous stimuli. Endogenously responsive drug‑controlled release hydrogels can sense environmental changes in diabetic wounds to achieve on‑demand drug release: glucose‑responsive hydrogels, pH‑sensitive hydrogels, reactive oxygen species‑responsive hydrogels, and matrix metalloproteinase‑responsive hydrogels perceive the microenvironmental changes in diabetic wounds and dynamically release anti‑inflammatory and antibacterial agents to promote the wound to enter a normal healing process. In addition, exogenous physical stimuli (e.g., electric field and ultrasound) enhance drug penetration and controlled release capability by modulating gel swelling, electrophoretic migration, or structural disintegration. These multimodal drug delivery systems, by spatiotemporally matching the dynamic changes of the wound microenvironment, synergistically regulate key processes including inflammation, antibacterial activity, angiogenesis, and tissue remodeling, significantly improving drug bioavailability and circumventing the risk of drug resistance, and are expected to promote the clinical translation of smart dressings.