Calcium phosphate processing strategies for the delivery of therapeutic agents

Regenerating bone lost to disease or trauma can be a significant challenge. A chronic bone infection is but one example of a debilitating disease leading to significant bone loss that is both difficult to eliminate, even with local intervention, and a threat to restoration of tissue or related joint function at the diseased site. Calcium phosphates have been recognized for years as good bone grafting materials since they are known to promote new bone growth when implanted in a bone defect. However, processing limitations have typically restricted their use in drug delivery applications. This program seeks to develop, through novel processing approaches, a class of degradable calcium phosphates (calcium polyphosphates) as temporary matrices for actively directing bone regeneration by the body's own cells while proactively combating disease conditions that may be responsible for bone loss. This will be achieved through the strategic incorporation and local release of drugs or therapeutic agents. This proposal builds on the previous development of antibiotic-loaded calcium phosphates, and specifically looks at the ability of these degradable matrices to deliver large molecules (proteins). Creating innovative antimicrobial calcium phosphates in the form of calcium phosphate-silver composite systems with potential broad applicability through processing manipulation is an additional focus of this work, as is enhancing the functional use of these matrices in self-setting calcium phosphate cements. Importantly, the approaches being developed here may serve to improve the quality of life for Canadians requiring such surgical interventions while taking pressure off an overburdened health care system by reducing costs associated with multiple surgeries. This research may also provide an opportunity to grow the medical device industry in Canada. Successful implementation of these strategies could have profound implications as well for the regeneration of complex tissue structures (eg., periodontal tissues around teeth) and the effective treatment of other debilitating bone diseases such as cancer (osteosarcomas).