Xie Xiao-Ting, Gao Cheng-Hao, Tan Lin-Fang, Chen Liang-Xi, Fan Jin-Xuan, Xiong Wei, Cheng Kai, Zhao Yuan-Di, Liu Bo
Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, PR China.
Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, PR China.
Biomaterials. 2025 May;316:122984. doi: 10.1016/j.biomaterials.2024.122984. Epub 2024 Dec 2.
The treatment of infected diabetic wounds remains a significant clinical challenge due to pathogen infection, excessive inflammation, and impaired angiogenesis with troubled extracellular matrix (ECM) - cell and cell - cell interaction. Herein, we prepared a Janus polypeptide-engineered hydrogel with programmable function driven by self-assembly of the same A domain. The hydrogel was composed of a V8-degradable ACA layer loaded with hybrid phages (ABC) for precise bacterial inhibition and a PCARGD layer loaded with Mn-based mineralized erythrocyte (PEM) for continuous supply oxygen on demand. The results of laser speckle contrast imaging, photoacoustic imaging, and hyperspectral imaging demonstrated that the ACA@BP-Ce6/PCAR@EM hydrogel (ABC/PEM) accelerated the reconstruction of normal skin structure by breaking the oxygen diffusion barrier and supplying oxygen on demand to promote angiogenesis and functionalization. In addition, in vitro and in vivo experiment results showed that the ABC/PEM hydrogel can mimic positive ECM - cell interaction to inhibit the polarization of macrophage towards M1-type to slow down the inflammatory process by down-regulated yes-associated protein (YAP), and relieve the mechanical tension of fibroblasts and keratinocytes. Finally, the ABC/PEM hydrogel promotes a healing rate of 98.83 % on day 21 and results in the number of dermal appendages being eight times that of the negative group. This work presents an effective strategy for diabetes-related chronic infected wound management.
由于病原体感染、过度炎症反应以及血管生成受损，同时伴有细胞外基质（ECM）-细胞和细胞-细胞相互作用紊乱，感染性糖尿病伤口的治疗仍然是一项重大的临床挑战。在此，我们制备了一种具有可编程功能的Janus多肽工程水凝胶，其由相同的A结构域自组装驱动。该水凝胶由负载杂合噬菌体（ABC）的V8可降解ACA层组成，用于精确抑制细菌，以及负载锰基矿化红细胞（PEM）的PCARGD层组成，用于按需持续供应氧气。激光散斑对比成像、光声成像和高光谱成像结果表明，ACA@BP-Ce6/PCAR@EM水凝胶（ABC/PEM）通过打破氧扩散屏障并按需供应氧气以促进血管生成和功能化，加速了正常皮肤结构的重建。此外，体外和体内实验结果表明，ABC/PEM水凝胶可以模拟正向ECM-细胞相互作用，通过下调Yes相关蛋白（YAP）来抑制巨噬细胞向M1型极化，从而减缓炎症过程，并减轻成纤维细胞和角质形成细胞的机械张力。最后，ABC/PEM水凝胶在第21天促进了98.83%的愈合率，真皮附属器数量是阴性组的八倍。这项工作为糖尿病相关慢性感染伤口的管理提供了一种有效的策略。
