Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30–70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ± 1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50–95%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC matrix. The tensile Young’s modulus (E), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.

中文翻译：

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含锶取代的纳米羟基磷灰石用于骨再生的可生物降解 3D 打印复合支架


大尺寸骨缺损的治疗很困难，并且由于可用性有限，获得自体移植物可能具有挑战性。在这种情况下，可以使用 3D 打印技术开发合成的患者专用骨替代品。在本研究中，我们开发了具有聚碳酸三亚甲基酯 （PTMC） 的光固化复合树脂，其中含有高比例的可生物降解生物活性锶取代纳米羟基磷灰石（SrHA，尺寸 30-70 nm）。然后，这些光固化树脂被用于使用数字光处理 （DLP） 技术开发高表面积 3D 打印的骨替代品。为了增加 3D 打印替代品的表面积，在 3D 打印支架/替代品中填充了单独的冷冻凝胶，并用骨形态发生蛋白 （BMP） 和唑来膦酸 （ZA） 的生物活性成分进行了功能化。在两个具有大骨缺损 （4 mm） 的治疗相关大鼠模型中，对支架的生物相容性和体内功能进行了体外测试。3D 打印支架的孔隙率分别为 60.1 ± 0.9%、72.9 ± 0.5% 和 74.3 ± 1.6%，处于松质骨范围内 （50-95%）。热重分析表明，在 PTMC 基体中制造了 HA 和 SrHA 浓度分别为 51.5 和 57.4 wt % 的 3D 打印复合材料。SrHA 和 HA 掺入 PTMC 基体后，拉伸杨氏模量 （E）、压缩模量和润湿性增加。体外和体内结果表明，整合到 PTMC 基质中的 SrHA 表现出良好的物理化学和生物学特性。 此外，发现骨活性分子功能化的 3D 打印复合支架具有足够的骨传导和骨诱导表面，在胫骨和颅骨缺损中均显示出增加的骨再生和缺损修复。因此，我们的研究结果支持使用 PTMC-SrHA 复合材料作为下一代患者特异性合成生物活性可生物降解骨替代品。