组织工程角膜基质的构建

Corneal stroma construction by tissue engineering

学术背景:角膜供体来源的匮乏及高危角膜移植术后的高排斥率限制了角膜移植的临床应用。构建具有良好生物学活性且能满足一定生理功能要求的组织工程角膜是近年来眼科的研究热点,而角膜基质组织的构建则是利用组织工程技术构建角膜的主要任务、难点和关键所在。目的:总结构建组织工程化角膜基质种子细胞及支架材料的研究进展。检索策略:应用计算机检索Pubmed数据库1980-01/2007-06的相关文献,检索词"cornealstroma;tissueengineering",限定文章语言种类为English。同时计算机检索中国期刊全文数据库、万方数据库1997-01/2007-06期间的相关文章,检索词"组织工程;角膜基质",限定文章语言种类为中文。共检索到59篇文献,对资料进行初审,纳入标准:①与构建组织工程角膜基质密切相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准:重复性研究。文献评价:文献的来源主要是构建组织工程角膜基质的实验。所选用的30篇文献中,5篇为综述,其余均为临床或基础实验研究。资料综合:①国内角膜盲患者众多,临床上对供体角膜的需求越发迫切。构建具有良好生物学活性且能满足一定生理功能要求的组织工程角膜具有重大的探索价值与临床实际应用意义。②自体或异体角膜基质细胞不仅是最早采用的而且是应用最为广泛的种子细胞。皮肤成纤维细胞应用于构建组织工程角膜基质的文献已见诸于报道。③作为支架材料,胶原、明胶及壳聚糖均有报道用于构建组织工程角膜基质。研究表明人工合成可降解高分子材料聚羟基乙酸材料与角膜基质细胞有较好的亲和力。④随着干细胞研究、材料科学及生物工程学等多学科的发展,组织工程角膜基质的构建越来越凸现其优越性,但它仍然面临许多挑战,比如:如何定向诱导多能干细胞分化为角膜基质细胞;角膜基质支架材料如何改良以保证良好的透明性;支架材料的生物学特性及理化性质需进一步研究。结论:组织工程角膜基质是构建组织工程角膜的重要基础,也预示着临床应用组织工程技术治疗角膜盲时代的到来。它将为解决异体角膜来源匮乏、高危角膜移植成功率低等临床问题提供新的思路。

BACKGROUND： The clinical application of corneal transplantation is restricted by the lacking of donor corneas and the poor prognosis after high-risk keratoplasty. Therefore, how to construct the bio-engineered cornea that has excellent compatibility provides a good vision. Corneal stroma is the key point of the construction of tissue-engineered cornea. OBJECTIVE： To review the advances on the seed cells and biomaterial scaffold of tissue-engineered corneal stroma. RETRIEVE STRATEGY： A computer-based online search of Pubmed was undertaken for the English articles published from January 1980 to June 2007 with the keywords of ＂corneal stroma, tissue engineering＂. Meanwhile, we searched CNKI database and Wanfang database for the Chinese articles dated from January 1997 to June 2007 with the same keywords in Chinese. Totally 59 articles were collected and after the first trail, only articles ①related with the construction of tissue-engineered corneal stroma and ②published in recently or in authoritative joumals were included. Repetitive researches were excluded. LITERATURE EVALUATION： The articles were mainly from the experiments of constructing tissue-engineered corneal stroma. In the 30 selected articles, 5 were review articles, and the others were clinical or basic experimental studies. DATA SYNTHESIS： ①There are many keratopathy-induced blind patients in domestic, and the clinical demand for donor corneas is urgent, Therefore, to construct the tissue-engineering cornea that has good bioactivity and could meet certain physiological function is significant for clinical application. ②Autologous or allogenic corneal stromal cells are the earliest and most widely used seed cells. It seems that skin fibroblasts may be another ideal candidate for the construction of tissue-engineered corneal stroma, ③lt is reported that biomaterials including collagen, gelatin and chitosan are used to construct the tissue-engineered corneal stroma. Some researchers reveal that keratocytes grow well on the degradable polyglycolic acid scaffold, ④The development of stem cell study, materials science and tissue engineering provides a good prospect for tissue-engineered corneal stroma, But there are still some problems unsolved like how to induce the stem cells to differentiate into keratocytes, how to modify the scaffold materials to maintain good transparence and the nature of biomaterials. CONCLUSION： Tissue-engineered corneal stroma is the key foundation of functional human corneal equivalents, indicating the era of tissue engineering technique to treat keratopathy-induced blindness. It would provide a new strategy for the management of contradiction between supply and demand of human cornea and the high-risk keratoplasty.