Tezcaner A, Hicks D
Department of Engineering Sciences, Middle East Technical University, Ankara 06531, Turkey.
J Biomed Mater Res A. 2008 Jul;86(1):170-81. doi: 10.1002/jbm.a.31600.
In developed countries the aging population faces increasing risks of blinding retinal diseases, for which there are few effective treatments available. Photoreceptor transplantation represents one approach, but generally results have been disappointing. We hypothesize that micropatterned biodegradable poly(L-lactic acid-co-glycolic acid)/poly(hydroxybutyrate-co-hydroxyvaleric acid) (PLGA-PHBV8) blend films could deliver photoreceptor cells in a more organized manner than bolus injections. Blending of PLGA and PHBV8 was used to optimize the degradation rate of the temporary template. At the end of 8 weeks, for both thin and thick films of PLGA-PHBV8 a 50% decrease of their initial weight with increasing water uptake was observed. When photoreceptor cells were seeded onto micropatterned PLGA-PHBV8 films with parallel grooves (21- and 42-microm-wide grooves and 20 microm ridge width and depth), the cells preferred laminin-deposited grooves to ridges and expressed rod- and cone-specific markers such as rhodopsin and arrestin. A loss in photoreceptor viability of 50% was observed after 7 days in culture. The effects of either retinal pigment epithelium (RPE)-derived or Muller glial cell-derived conditioned media or bFGF on the survival of photoreceptor cells seeded on PLGA-PHBV8 films were investigated. Addition of either RPE- and Muller-conditioned media increased statistically (p < 0.01) the viability of photoreceptor cells after 7 days of incubation. Our results suggest that such biodegradable micropatterned PLGA-PHBV8 blend films have a potential to deliver photoreceptor cells to the subretinal space and ensure laminar organization and maintenance of differentiation, and that incorporation of intrinsic factors within the scaffold would enhance the survival rate of transplanted cells.
在发达国家，老龄化人口面临致盲性视网膜疾病的风险不断增加，而针对这些疾病的有效治疗方法却很少。光感受器移植是一种治疗方法，但总体结果令人失望。我们假设，微图案化的可生物降解聚（L-乳酸-共-乙醇酸）/聚（3-羟基丁酸-共-3-羟基戊酸）（PLGA-PHBV8）共混膜能够比推注注射更有序地递送光感受器细胞。PLGA和PHBV8的共混用于优化临时模板的降解速率。在8周结束时，观察到PLGA-PHBV8的薄膜和厚膜随着吸水量增加，其初始重量均减少了50%。当将光感受器细胞接种到具有平行凹槽（21微米和42微米宽的凹槽以及20微米的脊宽和深度）的微图案化PLGA-PHBV8膜上时，细胞更喜欢沉积有层粘连蛋白的凹槽而非脊，并表达视紫红质和抑制蛋白等视杆和视锥特异性标志物。培养7天后，观察到光感受器活力丧失了50%。研究了视网膜色素上皮（RPE）衍生的或穆勒神经胶质细胞衍生的条件培养基或碱性成纤维细胞生长因子（bFGF）对接种在PLGA-PHBV8膜上的光感受器细胞存活的影响。添加RPE和穆勒条件培养基在孵育7天后均能使光感受器细胞的活力在统计学上显著提高（p < 0.01）。我们的结果表明，这种可生物降解的微图案化PLGA-PHBV8共混膜有潜力将光感受器细胞递送至视网膜下间隙，并确保层状组织和分化的维持，并且在支架中掺入内在因子将提高移植细胞的存活率。
