Ware H O T, Ding Y, Collins C, Akar B, Akbari N, Wang H, Duan C, Ameer G, Sun C
Department of Mechanical Engineering, Northwestern University, 2145 Sheridan Rd, Evanston, IL, 60208, USA.
Center for Advanced Regenerative Engineering (CARE), 2145 Sheridan Rd, Evanston, IL 60208, USA.
Mater Today Chem. 2022 Dec;26. doi: 10.1016/j.mtchem.2022.101231. Epub 2022 Nov 12.
With recent developments in materials engineering and additive manufacturing, the feasibility of patient-specific biomedical devices has increased substantially. Bioresorbable vascular stents/scaffolds (BVS), implants which reopen narrowed blood vessels, have seen considerable research in freeform fabrication as one such potentially customizable medical device. However, clinical requirements for stents place significant limits on manufacturing; the device must maintain the vessel's natural diameter once it has been reopened and must have sub-100 μm radial thickness to allow proper blood flow in small diameter vessels. Recent commercialization challenges for BVSs have highlighted the importance of meeting these requirements. For example, the first BVS marketed in the U.S.A., made from polylactide, had a radial thickness of 150 μm, which potentially contributed to negative side-effects and reduced efficacy. Thus, new bioresorbable materials and manufacturing strategies are required to fabricate BVSs that have sub-100 μm feature sizes that are mechanically competent and safe. In this work, we report the innovative use of a two-phase system that enables in situ formation of semicrystalline poly-l-lactic acid nanofibrous networks within a 3D printed polymeric matrix of a bioresorbable citrate-based biomaterial used for the first time in a resorbable medical device recently approved by the Food and Drug Administration. The optimized composite ink is compatible with the high-resolution micro-continuous liquid interphase production method with demonstrated smallest printable features of 80 μm. The resulting composite material has a significantly improved Young's modulus of 969.55 MPa at the fully hydrated state, a 108% improvement over the previously reported pure citrate-based biomaterial materials. We have successfully fabricated the BVS with strut thicknesses less than 100 μm and demonstrated that the stent can sustain applied vessel loading under physiological blood pressure conditions. The fabrication method can potentially be broadly applied to other biomedical devices.
随着材料工程和增材制造的最新发展，定制化生物医学设备的可行性已大幅提高。生物可吸收血管支架/支架（BVS）是一种可重新打开狭窄血管的植入物，作为一种潜在的可定制医疗设备，在自由成型制造方面已得到了大量研究。然而，支架的临床要求对制造提出了重大限制；该设备在重新打开血管后必须保持血管的自然直径，并且其径向厚度必须小于100μm，以便在小直径血管中实现正常的血液流动。BVS最近的商业化挑战凸显了满足这些要求的重要性。例如，在美国上市的首款由聚丙交酯制成的BVS，其径向厚度为150μm，这可能导致了负面副作用并降低了疗效。因此，需要新的生物可吸收材料和制造策略来制造具有小于100μm特征尺寸、机械性能良好且安全的BVS。在这项工作中，我们报告了一种两相系统的创新应用，该系统能够在3D打印的基于柠檬酸盐的生物可吸收生物材料的聚合物基质中原位形成半结晶聚-L-乳酸纳米纤维网络，这种生物材料首次用于最近获得美国食品药品监督管理局批准的可吸收医疗设备中。优化后的复合墨水与高分辨率微连续液相生产方法兼容，已证明其最小可打印特征为80μm。所得复合材料在完全水合状态下的杨氏模量显著提高，达到969.55MPa，比先前报道的纯柠檬酸盐基生物材料提高了108%。我们成功制造出了支柱厚度小于100μm的BVS，并证明该支架能够在生理血压条件下承受施加的血管负荷。该制造方法有可能广泛应用于其他生物医学设备。
