Powell Heather M, Supp Dorothy M, Boyce Steven T
Research Department, Shriners Burns Hospital, Cincinnati, OH 45229, USA.
Biomaterials. 2008 Mar;29(7):834-43. doi: 10.1016/j.biomaterials.2007.10.036. Epub 2007 Dec 3.
The treatment of massive full-thickness burns with engineered skin substitutes has shown promise in clinical trials. The majority of skin substitutes are comprised of fibroblasts and/or keratinocytes on collagen scaffolds, commonly generated by freeze drying which can generate significant structural heterogeneity. Electrospinning may generate collagen scaffolds with greater homogeneity. Skin substitutes were fabricated using either freeze-dried (FD) or electrospun (ES) collagen scaffolds. Cell distribution, proliferation, organization, and maturation were assessed on each scaffold type in vitro, and engraftment and healing of full thickness wounds in athymic mice were tested. In vitro evaluation of freeze-dried collagen skin substitutes (FCSS) and electrospun collagen skin substitutes (ECSS) revealed no significant differences in cell proliferation, surface hydration, or cellular organization between the ECSS and FCSS groups. Both groups exhibited excellent stratification with a continuous layer of basal keratinocytes present at the dermal-epidermal junction. After grafting to full thickness wounds in athymic mice, both skin substitutes had high rates of engraftment: 87.5% in the FCSS group and 100% in the ECSS group. Histological evaluation of wounds revealed that bovine collagen persisted in the wound at week 8 in the FCSS group while no bovine collagen was seen in the ECSS group. At 8 weeks post-grafting, the ECSS grafts were 61.3+/-7.9% original graft area whereas the FCSS grafts were 39.2+/-8.8% original area (p<0.01). These results indicate that ES scaffolds can be used to fabricate skin substitutes with optimal cellular organization and can potentially reduce wound contraction compared to FD scaffolds. These advantages may lead to reduced morbidity in patients treated with skin substitutes fabricated from ES collagen.
用工程皮肤替代物治疗大面积全层烧伤在临床试验中已显示出前景。大多数皮肤替代物由胶原支架上的成纤维细胞和/或角质形成细胞组成，通常通过冷冻干燥生成，这可能会产生显著的结构异质性。静电纺丝可能会生成具有更高均匀性的胶原支架。使用冷冻干燥（FD）或静电纺丝（ES）胶原支架制备皮肤替代物。在体外评估每种支架类型上的细胞分布、增殖、组织和成熟情况，并测试无胸腺小鼠全层伤口的植入和愈合情况。对冷冻干燥胶原皮肤替代物（FCSS）和静电纺丝胶原皮肤替代物（ECSS）的体外评估显示，ECSS组和FCSS组在细胞增殖、表面水合或细胞组织方面无显著差异。两组均表现出良好的分层，在真皮-表皮交界处有连续的基底角质形成细胞层。移植到无胸腺小鼠的全层伤口后，两种皮肤替代物的植入率都很高：FCSS组为87.5%，ECSS组为100%。伤口的组织学评估显示，FCSS组在第8周时伤口中仍存在牛胶原，而ECSS组未见牛胶原。移植后8周，ECSS移植物为原始移植物面积的61.3±7.9%，而FCSS移植物为原始面积的39.2±8.8%（p<0.01）。这些结果表明，与FD支架相比，ES支架可用于制造具有最佳细胞组织的皮肤替代物，并可能减少伤口收缩。这些优势可能会降低用ES胶原制备的皮肤替代物治疗的患者的发病率。
