Bowers D T, Chhabra P, Langman L, Botchwey E A, Brayman K L
Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, USA.
Transplant Proc. 2011 Nov;43(9):3285-7. doi: 10.1016/j.transproceed.2011.09.008.
Nanofiber scaffolds could improve islet transplant success by physically mimicking the shape of extracellular matrix and by acting as a drug-delivery vehicle. Scaffolds implanted in alternate transplant sites must be prevascularized or very quickly vascularized following transplantation to prevent hypoxia-induced islet necrosis. The local release of the S1P prodrug FTY720 induces diameter enlargement and increases in length density. The objective of this preliminary study was to evaluate length and diameter differences between diabetic and nondiabetic animals implanted with FTY720-containing electrospun scaffolds using intravital imaging of dorsal skinfold window chambers.
Electrospun mats of randomly oriented fibers we created from polymer solutions of PLAGA (50:50 LA:GA) with and without FTY720 loaded at a ratio of 1:200 (FTY720:PLAGA by wt). The implanted fiber mats were 4 mm in diameter and ∼0.2 mm thick. Increases in length density and vessel diameter were assessed by automated analysis of images over 7 days in RAVE, a Matlab program.
Image analysis of repeated measures of microvessel metrics demonstrated a significant increase in the length density from day 0 to day 7 in the moderately diabetic animals of this preliminary study (P < .05). Furthermore, significant differences in length density at day 0 and day 3 were found between recently STZ-induced moderately diabetic and nondiabetic animals in response to FTY720 local release (P < .05, Student t test).
Driving the islet revascularization process using local release of factors, such as FTY720, from biodegradable polymers makes an attractive system for the improvement of islet transplant success. Preliminary study results suggest that a recently induced moderately diabetic state may potentiate the mechanism by which local release of FTY720 from polymer fibers increases length density of microvessels. Therefore, local release of S1P receptor-targeted drugs is under further investigation for improvement of transplanted islet function.
纳米纤维支架可以通过物理模拟细胞外基质的形状以及作为药物递送载体来提高胰岛移植的成功率。植入替代移植部位的支架必须在移植前进行血管化或在移植后非常迅速地血管化，以防止缺氧诱导的胰岛坏死。鞘氨醇-1-磷酸（S1P）前药芬戈莫德（FTY720）的局部释放可诱导血管直径增大并增加长度密度。这项初步研究的目的是使用背部皮褶窗口室的活体成像来评估植入含FTY720的电纺支架的糖尿病动物和非糖尿病动物之间的长度和直径差异。
我们从聚乳酸-羟基乙酸共聚物（PLAGA，乳酸与乙醇酸比例为50:50）的聚合物溶液中制备了随机取向纤维的电纺垫，其中一些电纺垫按1:200（FTY720与PLAGA的重量比）的比例负载了FTY720，另一些未负载。植入的纤维垫直径为4毫米，厚度约为0.2毫米。通过Matlab程序RAVE对图像进行7天的自动分析，评估长度密度和血管直径的增加情况。
对微血管指标的重复测量进行图像分析表明，在这项初步研究的中度糖尿病动物中，从第0天到第7天长度密度显著增加（P < 0.05）。此外，在最近通过链脲佐菌素诱导的中度糖尿病动物和非糖尿病动物中，在第0天和第3天，对FTY720局部释放的反应中，长度密度存在显著差异（P < 0.05，学生t检验）。
利用可生物降解聚合物局部释放如FTY720等因子来驱动胰岛血管再生过程，为提高胰岛移植成功率提供了一个有吸引力的系统。初步研究结果表明，最近诱导的中度糖尿病状态可能增强了FTY720从聚合物纤维局部释放增加微血管长度密度的机制。因此，针对S1P受体的药物局部释放正在进一步研究，以改善移植胰岛的功能。
