Use of an in vitro model of tissue-engineered skin to investigate the mechanism of skin graft contraction
Use of an in vitro model of tissue-engineered skin to investigate the mechanism of skin graft contraction
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DOI：
10.1089/ten.2006.12.3119
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发表时间：
2006-11-01
影响因子：
--
通讯作者：
MacNeil, Sheila
中科院分区：
文献类型：
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作者：
Harrison, Caroline A.;Gossiel, Fatma;MacNeil, Sheila
导致关节活动度丧失和外观畸形的植皮收缩仍然是一个主要的临床问题。在这项研究中，我们使用人体皮肤组织工程模型作为研究皮肤收缩机制的模型，该模型基于接种了角质形成细胞和成纤维细胞的无菌成人真皮，该模型在体外 28 天内收缩高达 60%。研究了改变胶原蛋白合成、降解和交联的药物对收缩的影响。使用免疫测定技术测定胶原合成和降解。结果表明，皮肤收缩并不依赖于抑制胶原蛋白合成或刺激胶原蛋白降解，而是与胶原蛋白重塑有关。因此，用戊二醛降低真皮柔韧性会抑制细胞收缩真皮的能力。基质金属蛋白酶的抑制和赖氨酰氧化酶介导的胶原交联的抑制也是如此，但转谷氨酰胺酶介导的交联则不受抑制。总之，这种人体皮肤的体外模型使我们能够确定特定的交联途径作为预防体内移植物挛缩的可能药理学靶点。
Skin graft contraction leading to loss of joint mobility and cosmetic deformity remains a major clinical problem. In this study we used a tissue-engineered model of human skin, based on sterilized human adult dermis seeded with keratinocytes and fibroblasts, which contracts by up to 60% over 28 days in vitro, as a model to investigate the mechanism of skin contraction. Pharmacologic agents modifying collagen synthesis, degradation, and cross-linking were examined for their effect on contraction. Collagen synthesis and degradation were determined using immunoassay techniques. The results show that skin contraction was not dependent on inhibition of collagen synthesis or stimulation of collagen degradation, but was related to collagen remodelling. Thus, reducing dermal pliability with glutaraldehyde inhibited the ability of cells to contract the dermis. So did inhibition of matrix metalloproteinases and inhibition of lysyl oxidase-mediated collagen cross-linking, but not transglutaminase-mediated cross-linking. In summary, this in vitro model of human skin has allowed us to identify specific cross-linking pathways as possible pharmacologic targets for prevention of graft contracture in vivo.