Department of Chemical Engineering, University of Washington, Seattle, WA, 98195, USA; Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Biomaterials. 2021 Dec;279:121174. doi: 10.1016/j.biomaterials.2021.121174. Epub 2021 Oct 5.
Unmet needs for small diameter, non-biologic vascular grafts and the less-than-ideal performance of medium diameter grafts suggest opportunities for major improvements. Biomaterials that are mechanically matched to native blood vessels, reduce the foreign body capsule (FBC) and demonstrate improved integration and healing are expected to improve graft performance. In this study, we developed biostable, crosslinked polyurethane formulations and used them to fabricate scaffolds with precision-engineered 40 μm pores. We matched the scaffold mechanical properties with those of native blood vessels by optimizing the polyurethane compositions. We hypothesized that such scaffolds promote healing and mitigate the FBC. To test our hypothesis, polyurethanes with 40 μm pores, 100 μm pores, and non-porous slabs were implanted subcutaneously in mice for 3 weeks, and then were examined histologically. Our results show that 40 μm porous scaffolds elicit the highest level of angiogenesis, cellularization, and the least severe foreign body capsule (based on a refined assessment method). This study presents the first biomaterial with tuned mechanical properties and a precision engineered porous structure optimized for healing, thus can be ideal for pro-healing vascular grafts and in situ vascular engineering. In addition, these scaffolds may have wide applications in tissue engineering, drug delivery, and implantable device.
对于小直径、非生物血管移植物的未满足需求以及中直径移植物的不理想性能表明存在重大改进的机会。与天然血管在力学上匹配、减少异物囊(FBC)并表现出改善的整合和愈合的生物材料有望改善移植物的性能。在这项研究中,我们开发了生物稳定的交联聚氨酯配方,并使用它们制造了具有精密工程化 40μm 孔的支架。我们通过优化聚氨酯组成来匹配支架的机械性能与天然血管的机械性能。我们假设这种支架促进愈合并减轻异物囊。为了验证我们的假设,将具有 40μm 孔、100μm 孔和无孔平板的聚氨酯植入小鼠皮下 3 周,然后进行组织学检查。我们的结果表明,40μm 多孔支架引发了最高水平的血管生成、细胞化和最不严重的异物囊(基于改进的评估方法)。这项研究提出了第一个具有调谐机械性能和优化用于愈合的精密工程多孔结构的生物材料,因此非常适合促进愈合的血管移植物和原位血管工程。此外,这些支架可能在组织工程、药物输送和可植入装置中有广泛的应用。