Department of Materials Science and Engineering and The Ohio State University, Columbus, Ohio, USA.
Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA.
Tissue Eng Part A. 2020 Nov;26(21-22):1138-1146. doi: 10.1089/ten.TEA.2020.0090. Epub 2020 Jun 29.
For patients with large, full-thickness burn wounds, sufficient donor sites for autografting are not available, and thus, alternate strategies must be used to close these wounds. Cultured epithelial autografts (CEAs) can aid in closing these wounds but are often associated with slow deposition of basement membrane proteins, leading to blistering and graft loss. Rete ridges and dermal papillae present at the dermal-epidermal junction (DEJ) play a key role in epidermal adhesion and skin homeostasis. Promoting the development of an interdigitated DEJ may enhance basement membrane protein deposition and provide enhanced physical interlock of the epidermis and dermis. To develop a dermal template with stable dermal papillae, an electrospun collagen scaffold was seeded with human dermal fibroblasts. Ridged topographies were patterned into the cell-seeded dermal template using laser ablation, creating wide and shallow (ActiveFX) or narrow and deep (DeepFX) wells. Micropatterned or flat (control) dermal templates were combined with CEAs immediately before grafting to full-thickness excisional wounds on immunodeficient mice. CEAs grafted in conjunction with ridged templates showed rete ridge formation at 2 weeks after grafting and led to increased epidermal thickness, proliferation, and stemness compared to templates with a flat DEJ. As this technology is further developed, the dermal papilla-containing dermal templates may be utilized in combination with CEAs to improve adhesion and clinical function. Impact statement Cultured epithelial autografts (CEAs) serve as an adjunct to conventional split-thickness autograft in patients with very large burns, but they are susceptible to blistering that can reduce engraftment. Blistering results, in part, from relatively slow basement membrane deposition after grafting. This study demonstrates that basement membrane deposition and rete ridge formation are enhanced by combination of CEAs with a micropatterned, cell-seeded dermal template. These findings may lead to improved treatment and increased survival in patients with very large burns.
对于大面积全层烧伤患者，可用于自体移植的供体部位不足，因此必须采用替代策略来封闭这些伤口。培养的表皮移植物（CEA）可有助于封闭这些伤口，但通常与基底膜蛋白的沉积缓慢有关，导致水疱和移植物丢失。真皮-表皮交界处（DEJ）处的真皮嵴和真皮乳头在表皮粘附和皮肤稳态中起着关键作用。促进 DEJ 的相互交织发育可能会增强基底膜蛋白的沉积，并为表皮和真皮提供增强的物理互锁。为了开发具有稳定真皮乳头的真皮模板，使用激光烧蚀将人真皮成纤维细胞接种到电纺胶原支架上。使用激光烧蚀将脊状形貌图案化到细胞接种的真皮模板中，形成宽而浅（ActiveFX）或窄而深（DeepFX）的孔。微图案化或平坦（对照）的真皮模板在移植前与 CEA 结合，用于移植到免疫缺陷小鼠的全层切除伤口上。与具有平坦 DEJ 的模板相比，与脊状模板结合的 CEA 在移植后 2 周显示出真皮嵴的形成，并导致表皮厚度、增殖和干细胞特性增加。随着这项技术的进一步发展，包含真皮乳头的真皮模板可能与 CEA 结合使用，以改善粘附和临床功能。影响声明培养的表皮移植物（CEA）可作为大面积烧伤患者常规分层自体移植物的辅助物，但它们易发生水疱，从而降低移植物的成活率。水疱的形成部分是由于移植后基底膜的沉积相对较慢。这项研究表明，CEA 与微图案化、细胞接种的真皮模板结合使用可以增强基底膜的沉积和真皮嵴的形成。这些发现可能会改善大面积烧伤患者的治疗效果并提高生存率。
