Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, Uttar Pradesh, India.
Center for Environmental Science and Engineering, Indian Institute of Technology Kanpur, Kanpur 208016, Uttar Pradesh, India.
ACS Appl Mater Interfaces. 2024 Nov 27;16(47):65378-65393. doi: 10.1021/acsami.4c16195. Epub 2024 Nov 18.
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 (), 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.
治疗大尺寸骨缺损较为困难，由于来源有限，获取自体移植物可能颇具挑战性。在这种情况下，可以使用 3D 打印技术开发合成的、针对患者的骨替代物。在本研究中，我们开发了一种含有高比例可生物降解生物活性锶取代纳米羟基磷灰石（SrHA，粒径 30-70nm）的聚（三亚甲基碳酸酯）（PTMC）的光固化复合树脂。然后，我们使用数字光处理（DLP）技术，利用这些光固化树脂开发具有高比表面积的 3D 打印骨替代物。为了提高 3D 打印替代物的表面积，单独的冷冻凝胶以及负载骨形态发生蛋白（BMP）和唑来膦酸（ZA）等骨活性成分的冷冻凝胶被填充在 3D 打印支架/替代物内。我们在体外测试了这些支架的生物相容性，并在两种具有大骨缺损（4mm）的治疗相关大鼠模型中进行了体内功能测试。3D 打印支架的孔隙率分别为 PTMC、PTMC-HA 和 PTMC-SrHA 的 60.1±0.9%、72.9±0.5%和 74.3±1.6%，这与松质骨（50-95%）的范围一致。热重分析表明，在 PTMC 基质中分别制备了含有 51.5wt%和 57.4wt%HA 和 SrHA 的 3D 打印复合材料。在 PTMC 基质中掺入 SrHA 和 HA 后，拉伸杨氏模量（）、压缩模量和润湿性均增加。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，我们发现负载有骨活性分子的 3D 打印复合支架具有足够的骨传导性和骨诱导性表面，可增加胫骨和颅骨缺损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针对患者的合成生物活性可生物降解骨替代物。
