Yang Pu, Ju Yikun, Shen Naisi, Zhu Shuai, He Jiaqian, Yang Lingxiu, Lei Jiajie, He Xiaoli, Shao Wenjia, Lei Lanjie, Fang Bairong
Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
College of Materials Science and Engineering, Hunan University, Changsha, Hunan, 410082, China.
Adv Healthc Mater. 2025 Mar;14(7):e2403304. doi: 10.1002/adhm.202403304. Epub 2024 Oct 30.
Wound management has always been a challenge in the clinical treatment of diabetes. In this study, glucose oxidase (GOx) is grafted onto natural pullulan polysaccharides, and oxidization is carried out to form a self-healing hydrogel using carboxymethyl chitosan by means of reversible Schiff base covalent bonding. The smart-response drug release properties of this natural self-healing hydrogel are demonstrated in diabetic wounds by taking advantage of two key factors, namely the pH-responsive nature of Schiff base bonding and the fact that GOx reduces the pH in diabetic wounds. To further enhance the biological functions of the hydrogel dressing, exosomes (Exos) are introduced into the hydrogel system. The GOx present in the hydrogel system improves the high-glucose microenvironment of diabetic wounds, releasing HO to impart antimicrobial effects, and ensuring that the hydrogel realizes a smart-response function. The carboxymethyl chitosan component used to construct the hydrogel plays an effective antibacterial role. Moreover, the Exos loaded into the hydrogel effectively promotes neovascularization of the wound. The Exos also regulates macrophage polarization and reduces the levels of persistent inflammation in diabetic wounds. These results suggest that this smart responsive, multifunctional, and self-healing hydrogel dressing is ideal for the management of diabetic wounds.
伤口管理一直是糖尿病临床治疗中的一项挑战。在本研究中，将葡萄糖氧化酶（GOx）接枝到天然支链淀粉多糖上，并通过可逆席夫碱共价键合，利用羧甲基壳聚糖进行氧化以形成自愈合水凝胶。通过利用两个关键因素，即席夫碱键合的pH响应特性以及GOx降低糖尿病伤口pH值这一事实，在糖尿病伤口中证明了这种天然自愈合水凝胶的智能响应药物释放特性。为了进一步增强水凝胶敷料的生物学功能，将外泌体（Exos）引入水凝胶体系。水凝胶体系中存在的GOx改善了糖尿病伤口的高糖微环境，释放HO以发挥抗菌作用，并确保水凝胶实现智能响应功能。用于构建水凝胶的羧甲基壳聚糖成分发挥了有效的抗菌作用。此外，负载到水凝胶中的Exos有效地促进了伤口的新血管形成。Exos还调节巨噬细胞极化并降低糖尿病伤口中持续炎症的水平。这些结果表明，这种智能响应、多功能且自愈合的水凝胶敷料是糖尿病伤口管理的理想选择。
