The Laboratory for Therapeutic 3D Bioprinting, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States of America.
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, United States of America.
Biofabrication. 2024 Jul 16;16(4). doi: 10.1088/1758-5090/ad5f56.
Bone grafting is the most common treatment for repairing bone defects. However, current bone grafting methods have several drawbacks. Bone tissue engineering emerges as a promising solution to these problems. An ideal engineered bone graft should exhibit high mechanical strength, osteogenic properties, and pre-vascularization. Both top-down (using bulk scaffold) and bottom-up (using granular modules) approaches face challenges in fulfilling these requirements. In this paper, we propose a novel sectional modular bone approach to construct osteogenic, pre-vascularized bone grafts in anatomical shapes. We 3D-printed a series of rigid, thin, sectional, porous scaffolds from a biodegradable polymer, tailored to the dimensions of a femur bone shaft. These thin sectional modules promote efficient nutrition and waste removal due to a shorter diffusion distance. The modules were pre-vascularized viaangiogenesis, achieved through endothelial cell sprouting from the scaffold struts. Angiogenesis was further enhanced through co-culture with bioprinted fibroblast microtissues, which secreted pre-angiogenic growth factors. Sectional modules were assembled around a porous rod incorporated with Bone Morphogenetic Protein-2 (BMP-2), which released over 3 weeks, demonstrating sustained osteogenic activity. The assembled scaffold, in the anatomical shape of a human femur shaft, was pre-vascularized, osteogenic, and possessed high mechanical strength, supporting 12 times the average body weight. The feasibility of implanting the assembled bone graft was demonstrated using a 3D-printed femur bone defect model. Our method provides a novel modular engineering approach for regenerating tissues that require high mechanical strength and vascularization.
骨移植是修复骨缺损最常用的治疗方法。然而，目前的骨移植方法存在一些缺点。骨组织工程的出现为解决这些问题提供了一种有前途的方法。理想的工程化骨移植物应具有高机械强度、成骨特性和预血管化。自上而下（使用大块支架）和自下而上（使用颗粒模块）的方法在满足这些要求方面都面临挑战。在本文中，我们提出了一种新的节段性模块化骨方法，用于构建解剖形状的成骨、预血管化的骨移植物。我们使用可生物降解聚合物 3D 打印了一系列刚性、薄的、分段的多孔支架，这些支架的尺寸与股骨骨轴的尺寸相匹配。由于扩散距离较短，这些薄的分段模块促进了有效的营养和废物去除。通过血管生成使模块预血管化，这是通过支架支柱上的内皮细胞发芽实现的。通过与生物打印的成纤维细胞微组织共培养进一步增强血管生成，这些微组织分泌预血管生成生长因子。分段模块围绕着一个多孔棒组装，该多孔棒中掺入了骨形态发生蛋白 2（BMP-2），BMP-2 可以在 3 周内释放，表现出持续的成骨活性。组装的支架采用人体股骨轴的解剖形状，具有预血管化、成骨特性和高机械强度，可承受 12 倍于平均体重的压力。使用 3D 打印的股骨骨缺损模型证明了植入组装骨移植物的可行性。我们的方法为需要高机械强度和血管化的组织再生提供了一种新的模块化工程方法。
