基于3D打印技术制备载药多孔隙填充物治疗骨缺损与抗感染性及生物相容性评价研究

Bone defect is a common clinical disease, it is the necessary way to fill site of bone defects with external implants. Different parts of the bone defects were significant differences in morphological and mechanical, it was the lack of personalized parts for different parts of the design of bone defect filler, and bone defect treatment. Osteomyelitis is one of the major obstacles .The project is to be based on typical bone microstructure and bone biology, mechanical properties, through the analysis of micro-finite element, fluid mechanics, biomechanical to optimize the model design. By means of 3D printing with calcium carbonate / hydroxyapatite Stone / polycaprolactone, the construct has different parts of the filler with antibiotics to inhibit osteomyelitis. Its repair of bone defects is tested through bio-engineering, imaging, histology, and molecular biology, aiming at the design of matching anti-infective infusions for clinical treatment with different bone defects. The resulting filler is expected to have good Biocompatibility, biodegradable in vivo, can promote the growth of new bone, anti-infective features. The project for clinical 3D printing technology is implemented to promote and provide research data support ,and the treatment of patients with bone defects to provide personalized solutions.

骨缺损是一种临床常见病，以外部植入物填充骨缺损部位是治疗骨缺损的必经途径。不同部位的骨缺损具有显著的形态学、力学差异，目前缺少针对不同部位设计制备的个性化骨缺损填充物，同时骨缺损治疗过程中，骨髓炎的并发是治疗的重要障碍之一。本项目拟以典型骨微观结构和骨生物学、力学特性为基础,通过分析过微观有限元分析，流体力学分析，生物力学分析优化模型设计,通过3D打印为手段、以碳酸钙/羟基磷灰石/聚己内酯为主要原料构建针对不同缺损部位的填充物，过负载抗生素赋予其抗菌性以抑制骨髓炎。通过生物工程学、影像学、组织学、分子生物学检测其对骨缺损修复性能，旨在针对不同骨缺损设计与之相匹配的抗感染填充物用于临床治疗，预期所得的填充物具有良好的生物相容性、体内可降解、可促进新骨生长、抗感染的特点。通过本项目的实施为临床3D打印技术的推广及应用提供研究数据支撑，为骨缺损患者提供个性化解治疗方案。

骨缺损是一种临床常见病，以外部植入物填充骨缺损部位是治疗骨缺损的必经途径。研发更加适合3D打印成型工艺的生物医用材料，以及如何将高分子材料与3D打印技术更好地结合成为目前的研究热点。目的：通过3D打印技术制备β-磷酸三钙载药多孔支架，研究其体外性能及载药性能。方法：将聚己内酯（PCL）溶于二氯甲烷（DCM）后加入总量不同的β-磷酸三钙（β-TCP）得到打印墨水，通过溶剂挥发打印PCL：β-TCP=1：4的PCL/β-TCP/PDA多孔支架，测量其理化性质及药物负载量及负载时间，并通过细胞活性实验及动物实验测量其生物相容性及抗感染、促进骨骼愈合的性质。结论：5%PDA的边长 6mm 的正方形PCL/β-TCP其支架力学压缩应力-应变曲线平台处抗压强度为5.929±0.371，70%应变抗压强度为13.110±1.543 MPa，通过万古霉素测量其药物上载率为53.41%，有效药物释放时间约144小时，对于4周的骨缺损动物模型，植入支架的实验组比空白组骨体积分数明显上升,满足载药骨修补填充支架的要求。