Majumdar Shoumyo, Wang Xiaokun, Sommerfeld Sven D, Chae Jemin Jeremy, Athanasopoulou Evangelia-Nefeli, Shores Lucas S, Duan Xiaodong, Amzel L Mario, Stellacci Francesco, Schein Oliver, Guo Qiongyu, Singh Anirudha, Elisseeff Jennifer H
Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD 21231, USA.
Supramolecular Nanomaterials and Interfaces Laboratory, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
Adv Funct Mater. 2018 Oct 10;28(41). doi: 10.1002/adfm.201804076. Epub 2018 Aug 17.
Collagen-rich tissues in the cornea exhibit unique and highly organized extracellular matrix ultrastructures, which contribute to its high load-bearing capacity and light transmittance. Corneal collagen fibrils are controlled during development by small leucine-rich proteoglycans (SLRPs) that regulate the fibril diameter and spacing in order to achieve the unique optical transparency. Cyclodextrins (CDs) of varying size and chemical functionality for their ability to regulate collagen assembly during vitrification process are screened in order to create biosynthetic materials that mimic the native cornea structure. Addition of CD to collagen vitrigels produces materials with aligned fibers and lamellae similar to native cornea, resulting in mechanically robust and transparent materials. Biochemistry analysis revealed that CD interacts with hydrophobic amino acids in collagen to influence assembly and fibril organization. To translate the self-assembled collagen materials for cornea reconstruction, custom molds for gelation and vitrification are engineered to create CD/Col implants with curvature matching that of the cornea. Acellular CD/Col materials are implanted in a rabbit partial keratoplasty model with interrupted sutures. The implants demonstrate tissue integration and support re-epithelialization. Therefore, the addition of CD molecules regulates collagen self-assembly and provides a simple process to engineer corneal mimetic substitutes with advanced structural and functional properties.
角膜中富含胶原蛋白的组织呈现出独特且高度有序的细胞外基质超微结构，这使其具有高承载能力和透光性。在发育过程中，角膜胶原纤维受到富含亮氨酸的小分子蛋白聚糖（SLRPs）的调控，这些蛋白聚糖调节纤维直径和间距，以实现独特的光学透明度。为了制造模仿天然角膜结构的生物合成材料，人们筛选了具有不同大小和化学功能的环糊精（CDs），因为它们能够在玻璃化过程中调节胶原蛋白的组装。向胶原蛋白玻璃凝胶中添加CD会产生具有与天然角膜相似的排列纤维和薄片的材料，从而得到机械性能强大且透明的材料。生物化学分析表明，CD与胶原蛋白中的疏水氨基酸相互作用，影响组装和纤维组织。为了将自组装的胶原蛋白材料用于角膜重建，设计了用于凝胶化和玻璃化的定制模具，以制造曲率与角膜匹配的CD/Col植入物。将无细胞的CD/Col材料植入采用间断缝合的兔部分角膜移植模型中。植入物显示出组织整合并支持上皮再形成。因此，添加CD分子可调节胶原蛋白的自组装，并提供一个简单的过程来制造具有先进结构和功能特性的角膜模拟替代物。
