Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland.
J Biomed Mater Res B Appl Biomater. 2017 Nov;105(8):2618-2629. doi: 10.1002/jbm.b.33802. Epub 2016 Oct 20.
Localized delivery of stem cells is potentially a promising therapeutic strategy for regenerating damaged myocardium. Many studies focus on limiting the biologic component of cell loss, but few address the contribution of mechanical factors. This study investigates optimal parameters for retaining the largest volume of cell loaded hydrogels post intramyocardial injection, without compromising cell viability. In vitro, hydrogel was injected into porcine hearts using various needle designs. Hydrogel retention and distribution pattern was then determined. The two most promising needles were then investigated to understand the effect of needle geometry on stem cell viability. The needle to best impact cell viability was then used to investigate the effect of differing hydrogels on retention and distribution. Three-dimensional experimental modeling revealed needles with smaller diameter's to have greater poloxamer 407 hydrogel retention. No difference in retention existed among various needle designs of similar gauge, despite differences in bolus geometries. When hMSC's, embedded in fibrin hydrogel, were injected through helical and 26G bevel needles no difference in the percent of live cells was seen at 48 h. However, the helical group had almost half the metabolic activity of the 26G bevel group at both time points, and had a significant decline in the percent of live cells from 24 to 48 h. Varying gel type resulted in significantly more alginate being retained in the tissue in comparison to fibrin or poloxamer hydrogels. In conclusion, mechanical properties of injected hydrogels, and the diameter of the needle used, highly influences the volume of hydrogel retained. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2618-2629, 2017.
局部递送干细胞是一种有前途的治疗策略,可用于再生受损的心肌。许多研究都集中在限制细胞丢失的生物学成分上,但很少涉及机械因素的贡献。本研究探讨了在不影响细胞活力的情况下,经心肌内注射后保留载细胞水凝胶最大体积的最佳参数。在体外,使用各种针设计将水凝胶注入猪心。然后确定水凝胶的保留和分布模式。然后研究了两种最有前途的针,以了解针几何形状对干细胞活力的影响。然后使用最佳的针来研究不同水凝胶对保留和分布的影响。三维实验模型表明,直径较小的针具有更大的泊洛沙姆 407 水凝胶保留率。尽管不同的针设计具有不同的射流几何形状,但具有相似规格的各种针设计之间的保留率没有差异。当将嵌入纤维蛋白水凝胶中的 hMSC 通过螺旋和 26G 斜面针注射时,在 48 小时时没有看到活细胞的百分比有差异。然而,与 26G 斜面组相比,螺旋组在两个时间点的代谢活性几乎减半,并且从 24 小时到 48 小时活细胞的百分比显著下降。凝胶类型的变化导致与纤维蛋白或泊洛沙姆水凝胶相比,更多的藻酸盐保留在组织中。总之,注射水凝胶的机械性能和使用的针的直径高度影响水凝胶的保留量。 © 2016 Wiley Periodicals, Inc. J 生物医学材料研究部分 B: 应用生物材料,105B:2618-2629,2017。