Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Sciences, General Hospital of PLA, Beijing, PR China.
Biomaterials. 2010 Jul;31(21):5520-5. doi: 10.1016/j.biomaterials.2010.03.060. Epub 2010 Apr 15.
Despite the rapid development of engineered skin, such skin still lacks skin appendages. Sweat glands, one of the skin appendages, play key roles in the maintenance of homeostasis and temperature regulation. In this study, we tested whether sweat glands could be integrated into engineered skin constructs to improve the quality of tissue regeneration. Using gelatin microspheres(containing epidermal growth factor [EGF]) as multifunctional vehicles, we cultured sweat gland cells (SGCs) on them and delivered SGCs-microspheres complex (SMC) into the engineered skin construct, which was created in vitro by culturing human keratinocytes on top of a fibroblast-embedded collagen-based matrix in an organotypic co-culture model. This engineered skin construct was then transplanted onto full-thickness cutaneous wounds in an athymic murine model. EGF-loaded microspheres displayed more cellular growth-promoting efficiency, and thus SMC was an available means for SGCs delivery. Constitution of the engineered skin constructs formed a skin-like pattern in vitro. Remarkably, SMC could differentiate toward a sweat gland-like structure in vitro within the hybrid matrix. Furthermore, the degree of wound healing in mice with this skin construct implantation was better than that with controls. This engineered skin construct could be used as a promising tool for regeneration of sweat glands in skin repair and a valuable engineered strategy for constitution of appendage-containing engineered skin models.
尽管工程化皮肤发展迅速,但此类皮肤仍然缺乏皮肤附属物。汗腺作为皮肤附属物之一,在维持体内平衡和体温调节方面发挥着关键作用。在这项研究中,我们测试了是否可以将汗腺整合到工程化皮肤构建体中,以提高组织再生的质量。我们使用含有表皮生长因子 (EGF) 的明胶微球作为多功能载体,在其上培养汗腺细胞 (SGCs),并将 SGCs-微球复合物 (SMC) 递送至通过体外培养人角质形成细胞在成纤维细胞嵌入的基于胶原的基质上的器官型共培养模型中构建的工程化皮肤构建体中。然后,将这种工程化皮肤构建体移植到无胸腺鼠模型的全层皮肤创面。负载 EGF 的微球显示出更高的细胞生长促进效率,因此 SMC 是 SGCs 递送的一种可行方法。体外构建的工程化皮肤构建体形成了类似皮肤的图案。值得注意的是,SMC 可以在混合基质中体外分化为汗腺样结构。此外,这种皮肤构建体植入小鼠的伤口愈合程度优于对照组。这种工程化皮肤构建体可用作皮肤修复中汗腺再生的有前途的工具,也是构建含附属物的工程化皮肤模型的有价值的工程化策略。