纳米骨浆结合多喷嘴低温打印技术构建血管化骨诱导材料修复难治性骨缺损

Repair the difficult-cure bone defect with vascularized osteoinductive scaffold by the nano bone pulp and multi-nozzle low temperature printing. Because of the poor osteogenetic potential and bad blood supply, repairing a large segment of bone defect becomes the orthopedics clinical problem. Developing the biomimetic bone materials which could have the specific micro-nano structure, induce the osteogenic differentiation of bone marrow stromal cells (BMSC) and make the vascularization of implants is the key problem of repairing the difficult-cure bone defect in the tissue engineering area. On the base of past researches about biomimetic materials and peptides, according to the CT scan data of bone defect, the present research will use the nano hydroxyapatite/collagen (HAC) as the noumenon material, integrate the low temperature fabrication and multi-nozzle pneumatic assisted three dimensional printing technologies, load the BMP2-related peptide and vascular endothelial growth factor (VEGF), and finally develop the customized nano biomimetic artificial bone repair material which could have the osteoinductive activity and the capillary net. The present research will utilize the three dimensional printing technology to print the nano HAC, Bone morphogenetic protein 2(BMP2)-related peptide and VEGF nanocapsules synchronously, and make up the similar micro-nano structure and capillary net as the natural bone. It is the most important that the material could obtain the osteoinductive activity and the ability of vascularization. The new material could solve the key problem of repairing difficult-cure bone defect to a certain extent, and provide a good basis for the development of ideal bone repair material.

大段难治性骨缺损因成骨能力及血供差成为骨科临床难题。如何研制具有微纳米多级仿生结构的血管化骨诱导材料是亟待解决的关键问题。 本项目拟在长期从事纳米仿生材料研究及发明具有骨诱导活性的BMP2活性肽P24的基础上，根据目标骨缺损的CT扫描数据，以与天然骨基质最基本组分高度相似的、通过自组装矿化生成的纳米晶胶原基羟基磷灰石仿生骨(nHAC)为打印原材料，运用我校领先的低温沉积多喷嘴三维生物打印技术，定制化构建出与天然骨高度相似的从微纳米到毫厘米梯度渐变的仿生结构及三维互穿微血管通道，同步将具有良好控缓释特性的新型BMP2活性肽P28和可促血管再生的VEGF纳米囊，按需打印到支架和微血管的指定区域，从而制备出具有良好骨诱导活性的血管化纳米仿生骨诱导材料。 本设计在微纳结构高度仿生的同时，可实现多种生长因子的按需可控负载并保持良好活性调控种子细胞成骨和成血管，为很好地修复大段难治性骨缺损提供了可能

大段难治性骨缺损因成骨能力及血供差成为骨科临床难题。如何研制具有微纳米多级仿生结构的血管化骨诱导材料是亟待解决的关键问题。. 本项目在长期从事纳米仿生材料研究及发明具有骨诱导活性的 BMP2 活性肽 P24 的基础上，根据目标骨缺损的 CT 扫描数据，以与天然骨基质最基本组分高度相似的、通过自组装矿化生成的纳米晶胶原基羟基磷灰石仿生骨(nHAC)为打印原材料，运用低温沉积多喷嘴三维生物打印技术，成功定制化构建出与天然骨高度相似的从微纳米到毫厘米梯度渐变的仿生结构及三维互穿微血管通道，同步将具有良好控缓释特性的新型 BMP2 活性肽 P28 和可促血管再生的 VEGF 纳米囊，按需打印到支架和微血管的指定区域，制备出具有良好骨诱导活性的血管化纳米仿生骨诱导材料。本设计在微纳结构高度仿生的同时，可实现多种生长因子的按需可控负载并保持良好活性调控种子细胞成骨和成血管，为很好地修复大段难治性骨缺损提供了可能。