Alió del Barrio Jorge L, Chiesa Massimo, Gallego Ferrer Gloria, Garagorri Nerea, Briz Nerea, Fernandez-Delgado Jorge, Sancho-Tello Valls Maria, Botella Carmen Carda, García-Tuñón Ignacio, Bataille Laurent, Rodriguez Alejandra, Arnalich-Montiel Francisco, Gómez Ribelles Jose L, Antolinos-Turpín Carmen M, Gómez-Tejedor Jose A, Alió Jorge L, De Miguel Maria P
Department of Ophthalmology, Ramon y Cajal Hospital, Madrid, Spain.
J Biomed Mater Res A. 2015 Mar;103(3):1106-18. doi: 10.1002/jbm.a.35249. Epub 2014 Jun 18.
Currently available keratoprosthesis models (nonbiological corneal substitutes) have a less than 75% graft survival rate at 2 years. We aimed at developing a model for keratoprosthesis based on the use of poly(ethyl acrylate) (PEA)-based copolymers, extracellular matrix-protein coating and colonization with adipose-derived mesenchymal stem cells. Human adipose tissue derived mesenchymal stem cells (h-ADASC) colonization efficiency of seven PEA-based copolymers in combination with four extracellular matrix coatings were evaluated in vitro. Then, macroporous membranes composed of the optimal PEA subtypes and coating proteins were implanted inside rabbit cornea. After a 3-month follow-up, the animals were euthanized, and the clinical and histological biointegration of the implanted material were assessed. h-ADASC adhered and survived when cultured in all PEA-based macroporous membranes. The addition of high hydrophilicity to PEA membranes decreased h-ADASC colonization in vitro. PEA-based copolymer containing 10% hydroxyethyl acrylate (PEA-HEA10) or 10% acrylic acid (PEA-AAc10) monomeric units showed the best cellular colonization rates. Collagen plus keratan sulfate-coated polymers demonstrated enhanced cellular colonization respect to fibronectin, collagen, or uncoated PEAs. In vivo implantation of membranes resulted in an extrusion rate of 72% for PEA, 50% for PEA-AAc10, but remarkably of 0% for PEA-HEA10. h-ADASC survival was demonstrated in all the membranes after 3 months follow-up. A slight reduction in the extrusion rate of h-ADASC colonized materials was observed. No significant differences between the groups with and without h-ADASC were detected respect to transparency or neovascularization. We propose PEA with low hydroxylation as a scaffold for the anchoring ring of future keratoprosthesis.
目前可用的角膜假体模型（非生物角膜替代物）在2年时移植存活率低于75%。我们旨在开发一种基于聚（丙烯酸乙酯）（PEA）共聚物、细胞外基质蛋白涂层和脂肪来源间充质干细胞定植的角膜假体模型。在体外评估了七种基于PEA的共聚物与四种细胞外基质涂层组合时人脂肪组织来源间充质干细胞（h-ADASC）的定植效率。然后，将由最佳PEA亚型和涂层蛋白组成的大孔膜植入兔角膜内。经过3个月的随访后，对动物实施安乐死，并评估植入材料的临床和组织学生物整合情况。当在所有基于PEA的大孔膜中培养时，h-ADASC能黏附并存活。向PEA膜中添加高亲水性会降低体外h-ADASC的定植。含有10%丙烯酸羟乙酯（PEA-HEA10）或10%丙烯酸（PEA-AAc10）单体单元的基于PEA的共聚物显示出最佳的细胞定植率。与纤连蛋白、胶原蛋白或未涂层的PEA相比，胶原蛋白加硫酸角质素涂层的聚合物表现出增强的细胞定植。膜的体内植入导致PEA的挤出率为72%，PEA-AAc10为50%，但PEA-HEA10显著为0%。随访3个月后，在所有膜中均证实了h-ADASC的存活。观察到h-ADASC定植材料的挤出率略有降低。在透明度或新生血管方面，未检测到有h-ADASC组和无h-ADASC组之间存在显著差异。我们提议将低羟基化的PEA作为未来角膜假体固定环的支架。
