Biodegradable and elastomeric vascular grafts enable vascular remodeling
Biodegradable and elastomeric vascular grafts enable vascular remodeling
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可生物降解的弹性血管移植物能够实现血管重塑。
DOI：
10.1016/j.biomaterials.2018.08.063
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发表时间：
2018-11-01
期刊：
影响因子：
14
通讯作者：
Kong, Deling
中科院分区：
文献类型：
--
作者：
Zhu, Meifeng;Wu, Yifan;Kong, Deling
植入的移植物，包括血管替代物，不可避免地会经历宿主细胞的重塑。能够促进建设性重塑的移植物的设计仍然是再生医学领域的一个挑战。在这里，我们使用可生物降解的弹性聚合物聚（L-丙交酯-共-ε-己内酯）（PLCL）来开发具有周向排列的微纤维的血管移植物。该移植物表现出优异的操作性能和抗变形能力。植入大鼠腹主动脉后，在短时间内（4周）实现了移植引导的新动脉再生，细胞快速浸润和排列以及完全内皮化证明了这一点。在血管重塑过程中，检测到高比例的M2/M1巨噬细胞，促炎和抗炎细胞因子的表达在随访期间先升高，然后降低至正常水平。 12个月时，PLCL移植物几乎完全降解，形成了整合良好的新动脉，其特征与天然动脉相当，如透明的外观、同步搏动、致密有序的细胞外基质（ECM）排列、强而顺应的机械性能以及对药物的血管舒缩反应。总而言之，我们的策略代表了一种引导组织再生的新途径，通过设计移植物来通过控制支架的结构、降解和机械性能来促进组织重塑。
Implanted grafts, including vascular substitutes, inevitably experience remodeling by host cells. The design of grafts capable of promoting constructive remodeling remains a challenge within regenerative medicine. Here, we used a biodegradable elastic polymer, poly (L-lactide-co-epsilon-caprolactone) (PLCL), to develop a vascular graft with circumferentially aligned microfibers. The grafts exhibited excellent handling properties and resistance to deformation. Upon implantation in rat abdominal aorta, graft-guided neoartery regeneration was achieved in a short period (4 weeks) as evidenced by rapid cell infiltration and alignment, and complete endothelialization. During vascular remodeling, a high ratio of M2/M1 macrophage was detected, and the expression of pro-inflammatory and anti-inflammatory cytokines first increased and then decreased to normal level for the follow-up period. By 12 months, the PLCL grafts were almost completely degraded and a well-integrated neoartery was formed with characteristics comparable to native arteries, such as transparent appearance, synchronous pulsation, dense and orderly extracellular matrix (ECM) arrangement, strong and compliant mechanical properties, and vasomotor response to pharmacologic agents. Taken together, our strategy represents a new avenue for guided tissue regeneration by designing the grafts to promote tissue remodeling via controlling structure, degradation and mechanical properties of the scaffolds.