Dong Yabing, Liu Zhifei, Qi Fazhi, Jin Liang, Zhang Liang, Zhu Ningwen
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
ACS Biomater Sci Eng. 2019 May 13;5(5):2457-2465. doi: 10.1021/acsbiomaterials.8b01592. Epub 2019 Apr 18.
Full-thickness skin regeneration is still a clinical challenge for skin defects. Porcine small intestinal submucosa (SIS) has been exploited as a new scaffold for tissue reconstruction due to its excellent biocompatibility and ease of handling and modification. However, the application of SIS is dramatically impeded by its compact structure. Thus, a strategy for improving this property of SIS is highly desirable. Herein, SIS was recross-linked by a four-arm polyethylene glycol (fa-PEG) with succinimidyl glutarate-terminated branches into a three-dimensional (3D) bioactive sponge (SIS-PEG), which possessed porous 3D frameworks to mimic the structure of skin. The addition of a suitable proportion of fa-PEG endowed SIS with a uniform pore size, outstanding bioactivity, and flexible shape to promote a rapid healing of a mouse skin defect. Compared with SIS, the bioactive SIS-PEG sponge exhibited excellent mechanical stability and was less prone to collagenase degradation. Moreover, SIS-PEG provided a minimally invasive way to deliver stem cells for in situ wound repair. Remarkably, in vivo evaluation demonstrated that dissociated epidermal and dermal cells loaded with SIS-PEG could form reconstituted skin with regenerated hair after 21 days of treatment. The SIS-PEG bioactive sponge exhibited great potential for skin tissue engineering.
全层皮肤再生对于皮肤缺损而言仍是一项临床挑战。猪小肠黏膜下层（SIS）因其优异的生物相容性以及易于处理和修饰的特性，已被开发成为一种用于组织重建的新型支架材料。然而，SIS紧密的结构极大地阻碍了其应用。因此，迫切需要一种改善SIS这一特性的策略。在此，SIS通过具有琥珀酰亚胺戊二酸酯端基分支的四臂聚乙二醇（fa-PEG）进行再交联，形成一种三维（3D）生物活性海绵（SIS-PEG），其具有多孔的3D框架结构，可模拟皮肤结构。添加适当比例的fa-PEG赋予了SIS均匀的孔径、出色的生物活性以及灵活的形状，从而促进小鼠皮肤缺损的快速愈合。与SIS相比，生物活性SIS-PEG海绵表现出优异的机械稳定性，且更不易被胶原酶降解。此外，SIS-PEG为原位伤口修复提供了一种微创的干细胞递送方式。值得注意的是，体内评估表明，负载有SIS-PEG的解离表皮细胞和真皮细胞在治疗21天后能够形成带有再生毛发的重组皮肤。SIS-PEG生物活性海绵在皮肤组织工程方面展现出巨大潜力。
