State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, China.
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, PR China.
Biomaterials. 2018 Nov;183:306-318. doi: 10.1016/j.biomaterials.2018.08.063. Epub 2018 Sep 1.
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-ε-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.
植入的移植物,包括血管替代品,不可避免地会被宿主细胞重塑。设计能够促进建设性重塑的移植物仍然是再生医学中的一个挑战。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微纤维的血管移植物。这些移植物表现出良好的处理性能和抗变形能力。在大鼠腹主动脉内植入后,在短时间(4 周)内实现了移植物引导的新动脉再生,这表现在细胞快速浸润和排列,以及完全内皮化。在血管重塑过程中,检测到 M2/M1 巨噬细胞的高比例,促炎和抗炎细胞因子的表达首先增加,然后降至正常水平。12 个月后,PLCL 移植物几乎完全降解,形成了一个与天然动脉具有可比性的整合良好的新动脉,具有透明外观、同步搏动、密集有序的细胞外基质(ECM)排列、强而顺应的机械性能以及对药物的血管舒缩反应等特征。总之,我们的策略代表了一种通过设计移植物来促进组织重塑的新途径,通过控制支架的结构、降解和机械性能来实现。