A Bioengineering-Regenerative Medicine Approach for Ocular Surface Reconstruction Using a Functionalized Native Cornea-Derived Bio-Scaffold,Advanced Functional Materials

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A Bioengineering-Regenerative Medicine Approach for Ocular Surface Reconstruction Using a Functionalized Native Cornea-Derived Bio-Scaffold
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2023-09-04 , DOI: 10.1002/adfm.202304856
Mijeong Park ₁ , Alex Richardson ₁ , Naomi Delic ₁ , Kim Nguyen ₁ , Joanna Biazik ₂ , Richard Zhang ₁ , Lina Sprogyte ₁ , Lamia Nureen ₁ , Justin Lees ₃ , Angelica Fajardo ₄ , Ursula Kunicki ₄ , Stephanie L. Watson ₅ , John Males _{4,

5} , Nick Di Girolamo ₁

Affiliation

Limbal stem cell deficiency (LSCD) is characterized by the loss of limbal epithelial stem cells (LESCs) which compromises corneal transparency, leading to blindness. It cannot be treated with pharmacological or corneal transplantation interventions, instead a specialized stem cell (SC) therapy is needed to restore eye health and sight. Herein, a native cornea-derived biomaterial, a by-product of a laser refractive surgical procedure called small incision lenticule extraction is identified as a new cell delivery matrix. Culture conditions are optimized to facilitate LESC attachment, expansion and stratification, and their identity is immunophenotyped. Using electron microscopy, bio-constructs display stratification, similar to the architectural and cellular organization of a native mammalian cornea with formation of a basement membrane and an orderly array of collagen fibrils. Neuronal growth and depleted CD45⁺/CD14⁺ leukocytes on lenticules are also shown, suggesting that in transplantation experiments, they will re-innervate and not trigger a host-mediated immune response. Finally, human lenticules are geometrically customized to successfully fit them over a LSCD murine cornea ex vivo, during which they maintain curvature. The authors are poised to conduced similar studies in live mice using these and other carriers currently used in the clinic to compare SC therapy outcomes.

中文翻译：

使用功能化天然角膜衍生生物支架进行眼表重建的生物工程再生医学方法

角膜缘干细胞缺乏症（LSCD）的特点是角膜缘上皮干细胞（LESC）的丧失，从而损害角膜透明度，导致失明。它不能通过药物或角膜移植干预措施来治疗，而是需要专门的干细胞（SC）疗法来恢复眼睛健康和视力。在此，一种天然角膜衍生的生物材料，一种称为小切口微透镜提取的激光屈光手术的副产品，被认为是一种新的细胞输送基质。优化培养条件以促进 LESC 附着、扩增和分层，并且对其身份进行免疫表型分析。使用电子显微镜，生物结构显示分层，类似于天然哺乳动物角膜的结构和细胞组织，形成基底膜和有序排列的胶原纤维。还显示了微透镜上的神经元生长和耗尽的 CD45 ⁺ /CD14 ^{+白细胞，这表明在移植实验中，它们将重新受神经支配并且不会触发宿主介导的免疫反应。}最后，人类微透镜经过几何定制，成功地将它们安装在 LSCD 小鼠角膜上，在此期间它们保持曲率。作者准备使用这些载体和目前临床上使用的其他载体在活体小鼠中进行类似的研究，以比较 SC 治疗结果。

更新日期：2023-09-04

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