Development of a novel weight bearing bone biomaterial of calcium polyphosphate (CPP) infiltrated with dicalcium phosphate containing a bone anabolic drug.

目标：开发一种渗透有三斜磷钙石的CPP结构，其在其基质中掺入骨合成代谢缀合物药物，并使结构的机械性能最大化，优化其降解速率并增加骨长入速率。*背景资料：对于可生物降解的承重骨替代物存在强烈的需求，其用于填充骨空隙缺损、牙槽嵴增大、与脊柱融合手术相关联地使用的脊柱笼。多孔块状聚磷酸钙（CPP）结构可以满足这一需求，因为它具有生物相容性、骨传导性和强度。然而，CPP结构在骨环境中的溶解速率比骨形成速率慢得多。磷酸二钙生物材料，如三斜磷钙石，已被证明具有生物相容性和骨传导性。它们能够在体内更快地吸收，从而能够用新骨替代移植物。* 可行性：在上一个资助的任期内，我们已经报告了一种2步烧结/退火处理，用于形成多孔CPP作为可生物降解的骨替代物。为了提高降解速率而不损失CPP的强度，我们开始研究掺杂对机械性能和降解速率的影响。此外，我们的合作小组已经开发出一种方法来制造三斜磷钙石结构，其在其水泥基质中掺入双膦酸盐（阿仑膦酸盐）和称为C3的EP 4受体激动剂的新型骨合成代谢缀合物。其中一种三斜磷钙石结构已植入兔颅骨，并与骨表面整合。初步数据是非常有希望的，并且我们相信可以优化用含有C3的三斜磷钙石渗透的CPP的构建体以改善降解和功能。目的：本项目的具体目标是：（i）制造、修饰和表征CPP结构;（ii）通过用载有C3结合药物的三斜磷钙石渗透修饰CPP结构;（iii）评估结构内的结合物结合和稳定性;（iv）评估结构的降解;（v）通过骨植入初步研究显示结构的体内功效。意义：合适的生物可降解材料对于骨应用及其成功至关重要。定制CPP/三斜磷钙石/C3结构的性质将产生具有可再吸收骨植入物的理想机械和化学性质的材料，用于承重骨置换生物材料。

Goal: To develop a CPP construct infiltrated with monetite which incorporates in its matrix a bone anabolic conjugate drug and to maximize the mechanical properties of the construct and optimize its rate of degradation and increase the rate of bone ingrowth.***Background: There is a strong need for biodegradable load-bearing bone substitutes for filling bone void defects, alveolar ridge augmentation, spinal cages used in association with spinal fusion procedures. Porous bulk calcium polyphosphate (CPP) constructs may satisfy this need as it is biocompatible, osteoconductive and strong. However, CPP constructs dissolve at a rate much slower in the bone environment than bone formation rate. Dicalcium phosphate biomaterials, such as monetite, have been shown to be biocompatible and osteoconductive. They have the ability to resorb in vivo faster enabling the replacement of the graft by new bone. ***Feasibility: During the tenure of the previous grant, we have reported a 2-step sinter/anneal treatment for forming porous CPP as a biodegradable bone substitute. To increase the degradation rate without loss of strength of the CPP, we started a study to investigate the effect of doping on mechanical properties and degradation rate. In addition, our collaborative group has developed a method to fabricate monetite constructs that incorporates in their cement matrix a novel bone anabolic conjugate of a bisphosphonate (alendronate) and an EP4 receptor agonist known as C3. One of these constructs of monetite has been implanted on rabbit calvarium and has integrated with the bone surface. The preliminary data is very promising and we believe that constructs of CPP infiltrated with monetite containing C3 can be optimized to improve degradation and function.***Objectives: The specific objectives of this project would be: (i) Fabrication, modification and characterize CPP constructs; (ii) Modification of CPP constructs by infiltration with monetite loaded with C3 conjugate drug; (iii) Assess the conjugate binding and stability within the constructs; (iv) Assess degradation of the constructs; (v) Show in vivo efficacy of constructs via a bone implantation pilot study.***Significance: Suitable biodegradable materials are important for bone applications and their success. Tailoring the properties of the CPP/monetite/C3 constructs would produce materials with desirable mechanical and chemical properties of a resorbable bone implant for load bearing bone replacement biomaterials.