Unité mixte Inserm U1197 - Institut de Recherche Biomédicale des Armées (IRBA), Antenne Centre de Transfusion Sanguine des Armées, Clamart, France.
Celogos, Paris, France.
J Tissue Eng Regen Med. 2019 Aug;13(8):1362-1374. doi: 10.1002/term.2879. Epub 2019 Jun 14.
Cultured epithelial autografts (CEAs) represent a life-saving surgical technique for full-thickness skin burns covering more than 60% total body surface area. However, CEAs present numerous drawbacks leading to heavy cosmetic and functional sequelae. In our previous study, we showed that human plasma-based fibrin matrices (hPBM) could improve the reparative potential of CEAs. Therefore, in the present work, we sought to investigate the role of hPBM compared with fibrin from purified fibrinogen (FPF) or plastic support on epidermal substitute formation and engraftment. The use of hPBM for epidermal substitute culture improved keratinocyte migration, proliferation, and epidermal substitute organization to a better extent than FPF in vitro. Both fibrin matrices favored greater dermal-epidermal junction protein deposition and prevented their degradation. Keratinocyte differentiation was also decreased using both fibrin matrices. Basement membrane protein deposition was mainly influenced by matrix whereas growth factors released from fibrin especially by hPBM were shown to enhance in vitro keratinocyte migration, proliferation, and epidermal substitute organization. Ultimately, epidermal substitutes grown on hPBM displayed better engraftment rates than those cultured on FPF or on plastic support in a NOD-SCID model of acute wound with the formation of a functional dermal-epidermal junction. Together, these results show the positive impact of fibrin matrices and their released growth factor on epidermal substitute phenotype and grafting efficiency. Fibrin matrices, and especially hPBM, may therefore be of interest to favor the treatment of full-thickness burn patients.
培养的上皮自体移植物 (CEA) 是一种挽救生命的手术技术，适用于覆盖超过 60%总体表面积的全层皮肤烧伤。然而，CEA 存在许多缺点，导致严重的美容和功能后遗症。在我们之前的研究中，我们表明基于人血浆的纤维蛋白基质 (hPBM) 可以提高 CEA 的修复潜力。因此，在本工作中，我们试图研究 hPBM 与纯化纤维蛋白原的纤维蛋白 (FPF) 或塑料支架相比在表皮替代物形成和移植中的作用。hPBM 用于表皮替代物培养可改善体外角质形成细胞迁移、增殖和表皮替代物组织形成，优于 FPF。两种纤维蛋白基质都有利于更大程度地沉积真皮-表皮连接蛋白，并防止其降解。两种纤维蛋白基质还降低了角质形成细胞的分化。基底膜蛋白沉积主要受基质影响，而纤维蛋白释放的生长因子，特别是 hPBM，被证明可增强体外角质形成细胞迁移、增殖和表皮替代物组织形成。最终，在 NOD-SCID 急性创面模型中，与在 FPF 或塑料支架上培养的相比，在 hPBM 上生长的表皮替代物显示出更好的移植率，并形成功能正常的真皮-表皮连接。总之，这些结果表明纤维蛋白基质及其释放的生长因子对表皮替代物表型和移植效率有积极影响。纤维蛋白基质，尤其是 hPBM，可能有助于治疗全层烧伤患者。
