具有骨诱导和促血管化的可注射温敏性水凝胶/脱钙骨基质/掺锶聚磷酸钙复合物用于脊柱融合的研究

Aim at the practical issue of low fusion rate in the spinal fusion therapy, an injectable thermosensitive hydrogel/DBM/SCPP composite with osteoinductivity and angiogenesis was proposed for spinal fusion according to design and preparation of bone graft based on the study of applicant on strontium-doped calcium polyphosphate (SCPP) and demineralized bone matrix (DBM). Instead of the traditional design by using growth factors, angiogenesis of SCPP and osteoinductivity of DBM were combined to strength and acceleration of bone formation to increase spinal fusion rate. Meanwhile, thermosensitive hydrogel was used as a carrier to satisfy injectable handling in clinic. In this project, strontium amount, crystal type and particle size of SCPP were controlled to adjust the release profile of strontium ions, then in vitro cell models and in vivo ectopic bone formation model were used to investigate the effects of release of strontium on osteoinductivity and angiogenesis. Finally, angiogenesis, osteogenesis and spinal fusion ability were studied using an in vivo spinal fusion model. This study not only could provide a new idea and new method for design of bone graft, but also is of benefit to understand and explore the synergy mechanism of osteogenesis when combination use materials respectively with osteoinductivity and angiogenesis.

本项目针对脊柱融合治疗中融合率有待提高的实际问题，从骨移植材料的设计和制备出发，基于申请人对掺锶聚磷酸钙（SCPP）和脱钙骨基质（DBM）的研究基础，提出具有骨诱导和促血管化的可注射温敏性水凝胶/DBM/SCPP复合物用于脊柱融合的研究。拟突破传统使用生长因子的设计思路，将SCPP的促血管化作用与DBM的骨诱导性相结合来增强和加速骨的形成从而提高脊柱融合率。同时使用温敏性的水凝胶作载体以满足临床使用希望的可注射的操作要求。项目中拟通过控制SCPP的掺锶量、晶型和粒径来调控复合物中锶离子的释放；然后使用体外细胞模型和体内异位成骨模型研究复合物中锶离子的释放对骨诱导和促血管化的影响；最后通过体内脊柱融合模型研究复合物的促血管化、成骨能力和脊柱融合能力。本项目不仅为脊柱融合骨移植材料的设计和制备提供了一种新思路和新方法，同时也有助于认识和探讨骨诱导与促血管化材料联用的成骨协同作用机理。

本项目针对脊柱融合治疗中融合率有待提高的实际问题，从骨移植材料的设计和制备出发，基于申请人对掺锶聚磷酸钙（SCPP）和脱钙骨基质（DBM）的研究基础，提出具有骨诱导和促血管化的可注射温敏性水凝胶/DBM/SCPP复合物用于脊柱融合的研究。项目首先研究了复合物的制备和表征，重点在于控制锶离子的释放；然后使用体外细胞模型和体内异位成骨模型研究复合物中锶离子的释放对骨诱导和促血管化的影响；最后通过体内脊柱融合模型研究复合物的成骨能力、促血管化和脊柱融合能力。研究结果表明：通过控制不同掺锶量和晶型的SCPP，可制备出具有可控锶离子释放剂量的复合物；体外细胞实验筛选出的复合物可在保持骨诱导性的前提下，通过锶离子的释放来实现复合物的促血管化作用；体内肌肉异位成骨模型研究也表明复合物具有骨诱导性和促血管化功能；体内脊柱融合模型研究表明通过复合物具有的骨诱导性和促血管化作用，可实现提高脊柱融合率的目的。本项目不仅为脊柱融合骨移植材料的设计和制备提供了一种新思路和新方法，同时也有助于认识和探讨骨诱导与促血管化材料联用的作用机理。