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Composition of intraperitoneally implanted electrospun conduits modulates cellular elastic matrix generation

机译:腹膜内植入电纺导管的成分可调节细胞弹性基质的产生

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摘要

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.
机译:改善弹性基质的产生对于开发功能性组织工程化的血管移植至关重要。因此,这项研究通过将可能更多的弹性细胞募集到植入腹膜腔内的导管中,寻求一种在体内生长自体组织的策略。目的是确定电纺导管组成和透明质酸低聚物(HA-o)修饰对腹膜细胞募集及其表型和合成弹性基质的能力的影响。这些反应被评估为导管腹膜内植入时间的函数。这项研究表明,与巨噬细胞和平滑肌细胞(SMC)收缩标志物的表达趋势以及基质沉积相比,胶原蛋白与聚(ε-己内酯)(PCL)的掺混可促进更快的伤口愈合反应。仅PCL有更多的慢性反应。该结果以及弹性基质产量的增加,证明了将低至25%w / w胶原蛋白掺入导管的好处。此外,PCR分析证明了使用传统表型标记物区分成肌纤维细胞和SMC所面临的挑战。最后,与先前体外发现的显着反应不同,栓系HA-o的影响在炎性环境内受到限制。总之,这些结果证明了仔细控制植入的支架组合物和开发合适的HA-o递送方法的重要性。

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