Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.
Acta Biomater. 2014 Jan;10(1):163-72. doi: 10.1016/j.actbio.2013.08.042. Epub 2013 Sep 7.
Improving elastic matrix generation is critical to developing functional tissue engineered vascular grafts. Therefore, this study pursued a strategy to grow autologous tissue in vivo by recruiting potentially more elastogenic cells to conduits implanted within the peritoneal cavity. The goal was to determine the impacts of electrospun conduit composition and hyaluronan oligomer (HA-o) modification on the recruitment of peritoneal cells, and their phenotype and ability to synthesize elastic matrix. These responses were assessed as a function of conduit intra-peritoneal implantation time. This study showed that the blending of collagen with poly(ε-caprolactone) (PCL) promotes a faster wound healing response, as assessed by trends in expression of macrophage and smooth muscle cell (SMC) contractile markers and in matrix deposition, compared to the more chronic response for PCL alone. This result, along with the increase in elastic matrix production, demonstrates the benefits of incorporating as little as 25% w/w collagen into the conduit. In addition, PCR analysis demonstrated the challenges in differentiating between a myofibroblast and an SMC using traditional phenotypic markers. Finally, the impact of the tethered HA-o is limited within the inflammatory environment, unlike the significant response found previously in vitro. In conclusion, these results demonstrate the importance of both careful control of implanted scaffold composition and the development of appropriate delivery methods for HA-o.
改善弹性基质的生成对于开发功能性组织工程血管移植物至关重要。因此,本研究通过在腹腔内植入的导管招募潜在更多弹性细胞的策略,在体内生长自体组织。目的是确定电纺导管组成和透明质酸低聚物(HA-o)修饰对招募腹腔细胞及其表型和合成弹性基质的能力的影响。这些反应是作为导管腹腔内植入时间的函数来评估的。本研究表明,与单独的 PCL 相比,将胶原蛋白与聚(ε-己内酯)(PCL)混合可通过表达巨噬细胞和平滑肌细胞(SMC)收缩标志物和基质沉积的趋势,更快地促进伤口愈合反应,表现出更快的伤口愈合反应。这一结果,以及弹性基质产量的增加,表明在导管中掺入低至 25%w/w 的胶原蛋白就有好处。此外,PCR 分析表明,使用传统的表型标志物区分肌成纤维细胞和 SMC 具有挑战性。最后,与之前在体外发现的显著反应不同,束缚的 HA-o 的影响在炎症环境中是有限的。总之,这些结果表明,对植入支架组成的精细控制和 HA-o 的适当传递方法的开发都非常重要。