Laboratory of Experimental Ophthalmology, Department of Ophthalmology, Pius-Hospital, Carl von Ossietzky University, Oldenburg, Germany.
Institute of Pharmaceutical Technology, Technische Universität Braunschweig, Braunschweig, Germany.
J Tissue Eng Regen Med. 2020 Sep;14(9):1318-1332. doi: 10.1002/term.3103. Epub 2020 Jul 19.
The shortage of donor corneas as well as the limitations of tissue substitutes leads to the necessity to develop alternative materials for ocular surface reconstruction. Corneal surface substitutes must fulfill specific requirements such as high transparency, low immunogenicity, and mechanical stability combined with elasticity. This in vitro study evaluates a decellularized matrix secreted from human corneal fibroblasts (HCF) as an alternative material for ocular surface reconstruction. HCF from human donors were cultivated with the supplementation of vitamin C to form a stable and thick matrix. Furthermore, due to enhanced cultivation time, a three-dimensional like multilayered construct which partly mimics the complex structure of the corneal stroma could be generated. The formed human cell-based matrices (so-called cell sheets [CS]) were subsequently decellularized. The complete cell removal, collagen content, ultrastructure, and cell toxicity of the decellularized CS (DCS) as well as biomechanical properties were analyzed. Surgical feasibility was tested on enucleated porcine eyes. After decellularization and sterilization, a transparent, thick, cell free, and sterile tissue substitute resulted, which allowed expansion of limbal epithelial stem cells with no signs of cytotoxicity, and good surgical feasibility. DCS seem to be a promising new corneal tissue substitute derived from human cells without the limitation of donor material; however, future in vivo studies are necessary to further elucidate its potential for ocular surface reconstruction.
供体角膜短缺以及组织替代品的局限性导致需要开发用于眼表重建的替代材料。角膜表面替代品必须满足特定要求,例如高透明度、低免疫原性和机械稳定性与弹性相结合。本体外研究评估了从人角膜成纤维细胞(HCF)分泌的去细胞基质作为眼表重建的替代材料。用人捐赠者的 HCF 补充维生素 C 进行培养,以形成稳定且厚实的基质。此外,由于培养时间延长,可以生成类似于部分模仿角膜基质复杂结构的三维多层结构。随后对形成的基于人细胞的基质(所谓的细胞片[CS])进行去细胞处理。分析了去细胞 CS(DCS)的完整细胞去除、胶原含量、超微结构和细胞毒性以及生物力学特性。在猪眼眼球摘除后测试了手术可行性。去细胞和消毒后,得到了一种透明、厚实、无细胞和无菌的组织替代品,允许角膜缘上皮干细胞无细胞毒性地扩增,并且具有良好的手术可行性。DCS 似乎是一种有前途的新型角膜组织替代品,源自人细胞,没有供体材料的限制;然而,需要进一步的体内研究来阐明其用于眼表重建的潜力。