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

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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.