Boyce S T
Department of Surgery, University of Cincinnati College of Medicine, Ohio, USA.
Med Biol Eng Comput. 1998 Nov;36(6):791-800. doi: 10.1007/BF02518886.
Engineering skin substitutes provides a potential source of advanced therapies for the treatment of acute and chronic wounds. Cultured skin substitutes (CSS) consisting of human keratinocytes and fibroblasts attached to collagen-glycosaminoglycan substrates have been designed and tested in preclinical and clinical studies. Cell culture techniques follow general principles of primary culture and cryopreservation in liquid nitrogen for long-term storage. Biopolymer substrates are fabricated from xenogeneic (bovine) collagen and glycosaminoglycan that are lyophilised for storage until use. At maturity in air-exposed culture, CSS develop an epidermal barrier that is not statistically different from native human skin, as measured by surface electrical capacitance. Preclinical studies in athymic mice show rapid healing, expression of cytokines and regulation of pigmentation. Clinical studies in burn patients demonstrate a qualitative outcome with autologous skin that is not different from 1:4 meshed, split-thickness autograft skin, and with a quantitative advantage over autograft skin in the ratio of healed skin to biopsy areas. Chronic wounds resulting from diabetes or venous stasis have been closed successfully with allogeneic CSS prepared from cryopreserved skin cells. These results define the therapeutic benefits of cultured skin substitutes prepared with skin cells from the patient or from cadaver donors. Future directions include genetic modification of transplanted cells to improve wound healing transiently or to deliver gene products systemically.
工程化皮肤替代物为急性和慢性伤口的治疗提供了一种先进治疗方法的潜在来源。由附着在胶原-糖胺聚糖基质上的人角质形成细胞和成纤维细胞组成的培养皮肤替代物（CSS）已在临床前和临床研究中进行了设计和测试。细胞培养技术遵循原代培养和液氮冷冻保存以长期储存的一般原则。生物聚合物基质由异种（牛）胶原和糖胺聚糖制成，经冻干保存直至使用。在暴露于空气中的培养成熟时，通过表面电容测量，CSS形成的表皮屏障与天然人类皮肤在统计学上无差异。无胸腺小鼠的临床前研究显示愈合迅速、细胞因子表达和色素沉着调节。烧伤患者的临床研究表明，与1:4网状、中厚自体移植皮肤相比，自体皮肤的定性结果无差异，且在愈合皮肤与活检区域的比例上比自体移植皮肤具有定量优势。由冷冻保存的皮肤细胞制备的同种异体CSS已成功闭合糖尿病或静脉淤滞引起的慢性伤口。这些结果确定了用患者或尸体供体的皮肤细胞制备的培养皮肤替代物的治疗益处。未来的方向包括对移植细胞进行基因改造，以暂时改善伤口愈合或全身递送基因产物。
