Skin Engineering Laboratory, Adult Burn Centre, Royal Adelaide Hospital, SA, Australia.
Faculty of Health Sciences, The University of Adelaide, SA, Australia.
J Burn Care Res. 2021 Nov 24;42(6):1199-1209. doi: 10.1093/jbcr/irab034.
Extensive deep-burn management with a two-stage strategy can reduce reliance on skin autografts; a biodegradable polyurethane scaffold to actively temporize the wound and later an autologous composite cultured skin (CCS) for definitive closure. The materials fulfilling each stage have undergone in vitro and in vivo pretesting in "small" large animal wounds. For humans, producing multiple, large CCSs requires a specialized bioreactor. This article reports a system used to close large porcine wounds. Three Large White pigs were used, each with two wounds (24.5 cm × 12 cm) into which biodegradable dermal scaffolds were implanted. A sample from discarded tissue allowed isolation/culture of autologous fibroblasts and keratinocytes. CCS production began by presoaking a 1-mm-thick biodegradable polyurethane foam in autologous plasma. In the bioreactor cassette, fibroblasts were seeded into the matrix with thrombin until established, followed by keratinocytes. The CCSs were applied onto integrated dermal scaffolds on day 35, alongside a sheet skin graft (30% of one wound). Serial punch biopsies, trans-epidermal water loss readings (TEWL), and wound measurements indicated epithelialization. During dermal scaffold integration, negligible wound contraction was observed (average 4.5%). After CCS transplantation, the control skin grafts were "taken" by day 11 when visible islands of epithelium were clinically observed on 2/3 CCSs. Closure was confirmed histologically, with complete epithelialization by day 63 post-CCS transplantation (CCS TEWL ~ normal skin average 11.9 g/m2h). Four of six wounds demonstrated closure with robust, stratified epithelium. Generating large pieces of CCS capable of healing large wounds is thus possible using a specialized designed bioreactor.
采用两阶段策略的广泛深度烧伤管理可以减少对自体皮片的依赖；生物可降解的聚氨酯支架可主动临时处理创面，随后使用自体复合培养皮（CCS）进行确定性闭合。满足每一阶段要求的材料已在“小型”大动物创面的体外和体内进行了预测试。对于人类而言，制造多个大面积 CCS 需要专门的生物反应器。本文报告了一种用于闭合大面积猪创面的系统。使用了 3 头大白猪，每头猪有两个创面（24.5 cm×12 cm），其中植入了生物可降解的真皮支架。从废弃组织中取出的样本允许分离/培养自体成纤维细胞和角质形成细胞。CCS 的生产始于将 1 毫米厚的生物可降解聚氨酯泡沫浸泡在自体血浆中。在生物反应器盒中，将成纤维细胞与凝血酶一起播种到基质中，直到建立起来，然后播种角质形成细胞。CCS 于第 35 天应用于整合的真皮支架上，同时应用片状皮片移植物（一个创面的 30%）。连续的皮肤打孔活检、经皮水分丢失读数（TEWL）和创面测量表明上皮化。在真皮支架整合期间，观察到创面收缩很小（平均 4.5%）。CCS 移植后，当在 2/3 的 CCS 上临床观察到可见的上皮岛时，对照皮片移植物于第 11 天被“吸收”。组织学证实了闭合，CCS 移植后第 63 天，上皮化完全，CCS TEWL~正常皮肤平均 11.9 g/m2h）。6 个创面中的 4 个表现出闭合，具有坚固的、分层的上皮。使用专门设计的生物反应器，可实现大面积 CCS 的制造，从而能够治疗大面积创面。
