Shu Qiu-Hao, Zuo Rong-Tai, Chu Min, Shi Jing-Jing, Ke Qin-Fei, Guan Jun-Jie, Guo Ya-Ping
The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China.
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Biomater Adv. 2023 Nov;154:213640. doi: 10.1016/j.bioadv.2023.213640. Epub 2023 Sep 28.
Diabetic complications with high-glucose status (HGS) cause the dysregulated autophagy and excessive apoptosis of multiple-type cells, leading to the difficulty in wound self-healing. Herein, we firstly developed fiber-reinforced gelatin (GEL)/β-cyclodextrin (β-CD) therapeutic hydrogels by the modification of platelet-rich plasma exosomes (PRP-EXOs). The GEL fibers that were uniformly dispersed within the GEL/β-CD hydrogels remarkably enhanced the compression strengths and viscoelasticity. The PRP-EXOs were encapsulated in the hydrogels via the covalent crosslinking between the PRP-EXOs and genipin. The diabetic rat models demonstrated that the GEL/β-CD hydrogels and PRP-EXOs cooperatively promoted diabetic wound healing. On the one hand, the GEL/β-CD hydrogels provided the biocompatible microenvironments and active components for cell adhesion, proliferation and skin tissue regeneration. On the other hand, the PRP-EXOs in the therapeutic hydrogels significantly activated the autophagy and inhibited the apoptosis of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs). The activation of autophagy and inhibition of apoptosis in HUVECs and HSFs induced the blood vessel creation, collagen formation and re-epithelialization. Taken together, this work proved that the incorporation of PRP-EXOs in a wound dressing was an effective strategy to regulate autophagy and apoptosis, and provide a novel therapeutic platform for diabetic wound healing.
高血糖状态（HGS）引发的糖尿病并发症会导致多种类型细胞的自噬失调和过度凋亡，从而造成伤口自我愈合困难。在此，我们首先通过对富含血小板血浆外泌体（PRP - EXOs）进行修饰，制备了纤维增强明胶（GEL）/β - 环糊精（β - CD）治疗性水凝胶。均匀分散在GEL/β - CD水凝胶中的GEL纤维显著增强了抗压强度和粘弹性。PRP - EXOs通过与京尼平之间的共价交联被封装在水凝胶中。糖尿病大鼠模型表明，GEL/β - CD水凝胶和PRP - EXOs协同促进糖尿病伤口愈合。一方面，GEL/β - CD水凝胶为细胞黏附、增殖和皮肤组织再生提供了生物相容性微环境和活性成分。另一方面，治疗性水凝胶中的PRP - EXOs显著激活了人脐静脉内皮细胞（HUVECs）和人皮肤成纤维细胞（HSFs）的自噬并抑制其凋亡。HUVECs和HSFs中自噬的激活和凋亡的抑制诱导了血管生成、胶原蛋白形成和再上皮化。综上所述，这项工作证明在伤口敷料中加入PRP - EXOs是调节自噬和凋亡的有效策略，并为糖尿病伤口愈合提供了一个新的治疗平台。
