Wu Xiangyi, Zhu Haofang, Che Junyi, Xu Ye, Tan Qian, Zhao Yuanjin
Department of Burns and Plastic Surgery, Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210002, China.
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, China.
Bioact Mater. 2023 Mar 3;26:159-168. doi: 10.1016/j.bioactmat.2023.02.031. eCollection 2023 Aug.
Stem cell therapies have made great progress in the treatment of diabetic wounds during recent decades, while their short in vivo residence, alloimmune reactions, undesired behaviors, and dramatic losses of cell functions still hinder the translation of them into clinic. Here, inspired by the natural components of stem cell niches, we presented novel microfluidic hydrogel microcarriers with extracellular matrix (ECM)-like composition and adipose-derived stem cells (ADSCs) encapsulation for diabetic wound healing. As the hydrogel was synthesized by conjugating hyaluronic acid methacryloyl (HAMA) onto the Fibronectin (FN) molecule chain (FN-HAMA), the laden ADSCs in the microcarriers showed improved bioactivities and pro-regenerative capabilities. Based on these features, we have demonstrated that these ADSCs microcarriers exhibited significant promotion of neovascularization, follicular rejuvenation, and collagen deposition in a mouse diabetic wound model. These results indicated that the stem cell niche-inspired FN-HAMA microcarriers with ADSCs encapsulation have great clinical potential for diabetic wound treatment.
近几十年来,干细胞疗法在糖尿病伤口治疗方面取得了巨大进展,但其在体内停留时间短、同种免疫反应、不良行为以及细胞功能的显著丧失仍然阻碍了它们向临床的转化。在此,受干细胞微环境天然成分的启发,我们提出了具有细胞外基质(ECM)样组成和封装脂肪干细胞(ADSCs)的新型微流控水凝胶微载体,用于糖尿病伤口愈合。由于水凝胶是通过将甲基丙烯酰化透明质酸(HAMA)共轭到纤连蛋白(FN)分子链(FN-HAMA)上合成的,微载体中负载的ADSCs表现出改善的生物活性和促再生能力。基于这些特性,我们已经证明这些ADSCs微载体在小鼠糖尿病伤口模型中显著促进了新血管形成、毛囊再生和胶原蛋白沉积。这些结果表明,具有封装ADSCs的受干细胞微环境启发的FN-HAMA微载体在糖尿病伤口治疗方面具有巨大的临床潜力。