Burn Institute, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Republic of Korea.
Biomed Mater. 2018 Apr 17;13(4):045007. doi: 10.1088/1748-605X/aaac37.
The use of artificial dermis as a skin substitute is a field of active study, as acellular dermal matrices from cadavers are susceptible to infection owing to their human origin. One such alternative dermal replacement scaffold, INSUREGRAF, is derived primarily from extracellular matrix proteins such as collagen and elastin and has been clinically used to treat severe skin wounds such as burns. This scaffold has proven to be useful to minimize wound contraction and scar formation owing to its biocompatibility, interconnected pore structure, sufficient biodegradability, and suitable mechanical properties. However, INSUREGRAF does not provide scar-free wound healing in cases of severe skin damage such as full-thickness (FT) excision. Considering that the efficient recruitment of fibroblasts and keratinocytes into a wound site represents a critical step in the regeneration of damaged skin, we attempted to enhance the efficiency for wound healing by fabricating growth factor-functionalized INSUREGRAF. In particular, we utilized epidermal growth factor (EGF) and an EGF family member, neuregulin-1 (NRG1), not previously studied in the context of wound healing, whose cellular role is to promote proliferation and migration in fibroblasts and keratinocytes. Both artificial dermis-growth factor combinations led to efficient recruitment of fibroblasts and keratinocytes into a wound site during the early steps of skin regeneration. Notably, EGF- or NRG1-functionalized INSUREGRAF induced rapid proliferation of skin cells in an ERK pathway-dependent manner and exhibited efficient wound healing in a Sprague-Dawley rat FT excision and grafting model. These results provide the foundation for expanding the use of growth factor-functionalized INSUREGRAF to clinical application in cases of severe skin injury.
作为一种皮肤替代物，人工真皮的应用是一个活跃的研究领域，因为源自尸体的去细胞真皮基质由于其人类来源而易受感染。一种替代真皮替代支架 INSUREGRAF 主要源自细胞外基质蛋白，如胶原蛋白和弹性蛋白，已在临床上用于治疗严重的皮肤创伤，如烧伤。由于其生物相容性、相互连接的孔结构、足够的生物降解性和合适的机械性能，该支架已被证明有助于最大限度地减少伤口收缩和瘢痕形成。然而，在全层（FT）切除等严重皮肤损伤的情况下，INSUREGRAF 并不能实现无瘢痕的伤口愈合。考虑到成纤维细胞和角质形成细胞有效地募集到伤口部位是受损皮肤再生的关键步骤，我们试图通过制造生长因子功能化的 INSUREGRAF 来提高伤口愈合的效率。特别是，我们利用了表皮生长因子（EGF）和一种 EGF 家族成员神经调节蛋白-1（NRG1），它们以前没有在伤口愈合的背景下研究过，其细胞作用是促进成纤维细胞和角质形成细胞的增殖和迁移。这两种人工真皮-生长因子组合在皮肤再生的早期步骤中，都能有效地将成纤维细胞和角质形成细胞募集到伤口部位。值得注意的是，EGF 或 NRG1 功能化的 INSUREGRAF 以 ERK 途径依赖性的方式诱导皮肤细胞的快速增殖，并在 Sprague-Dawley 大鼠 FT 切除和移植模型中表现出有效的伤口愈合。这些结果为将生长因子功能化的 INSUREGRAF 扩展到严重皮肤损伤的临床应用提供了基础。
