The formulation of a bioresponsive ceramic bone replacement

[摘要] The long-term stability and brittle nature of ceramic bone replacements in physiological conditions makes them prone to mechanical failure. These problems have led to the development of bioresorbable bone replacement materials. Bioresorbable biomaterials are expected to degrade at a rate which is proportional to the rate of formation of new bone tissue. In the majority of cases, however, resorption is driven by simple dissolution and so it is difficult to ensure an appropriate degradation rate for all patients. This thesis seeks to develop a material that can degrade in response to the bone formation process, thus linking implant resorption to tissue formation. We have shown that this can be achieved by linking implant resorption to a biological stimulus, such as the enzyme alkaline phosphatase (ALP), which is found on the surface of bone forming cells (osteoblasts). ALP causes bone mineralisation by removing the pyrophosphate (P\(_2\)O\(_7\)\(^4\)\(^-\)) ion, a known inhibitor to calcium phosphate formation. By removing the P\(_2\)O\(_7\)\(^4\)\(^-\) P2O74- ions from solution the dissolution of calcium pyrophosphate ((Ca\(_2\)P\(_2\)O\(_7\)\(^4\)\(^-\)) crystals were accelerated in accordance with Le Chetalier's principle. We demonstrated that for this accelerated dissolution to occur, the ALP did not require access to the crystal surface. This is contrary to previous work which suggested that CPPD dissolution occurred as a result of ALP cleaving the crystal surface. Bulk (Ca\(_2\)P\(_2\)O\(_7\)\ ceramics were successfully produced by sintering brushite cement at temperatures ≥ 400°C, the dissolution of which could accelerated in the presence of ALP but was heavily dependent on material specific surface area. The process of sintering limits the possibility of producing biomaterials of complex morphology; therefore the final part of this thesis involved the fabrication of ((Ca\(_2\)P\(_2\)O\(_7\) ceramic using stereolithography.

[发布机构] University:University of Birmingham;Department:School of Chemical Engineering

[关键词] T Technology;TP Chemical technology