Calcium phosphate processing strategies for the delivery of therapeutic agents

再生因疾病或创伤而失去的骨骼可能是一个巨大的挑战。慢性骨感染只是导致严重骨丢失的一种衰弱疾病，这种疾病即使通过局部干预也很难消除，并威胁到患病部位组织或相关关节功能的恢复。多年来，磷酸钙一直被认为是良好的骨移植材料，因为人们知道，当植入骨缺损处时，它们可以促进新骨生长。然而，加工限制通常限制了它们在药物输送应用中的使用。该计划寻求通过新的加工方法开发一类可降解的磷酸钙(聚磷酸钙)作为临时基质，用于积极指导身体自身细胞的骨再生，同时主动对抗可能导致骨丢失的疾病条件。这将通过战略性合并和在当地释放药物或治疗剂来实现。这项建议建立在先前开发的抗生素负载磷酸钙的基础上，并特别着眼于这些可降解基质输送大分子(蛋白质)的能力。通过加工操作创造具有潜在广泛适用性的磷酸钙-银复合体系形式的创新型抗菌磷酸钙是这项工作的另一个重点，也是加强这些基质在自固化磷酸钙粘结剂中的功能使用。重要的是，这里正在开发的方法可能有助于改善需要此类手术干预的加拿大人的生活质量，同时通过减少与多次手术相关的成本来缓解不堪重负的医疗体系的压力。这项研究也可能为加拿大医疗器械行业的发展提供机会。这些策略的成功实施也可能对复杂组织结构的再生(如牙齿周围的牙周组织)和其他令人衰弱的骨骼疾病(如癌症(骨肉瘤))的有效治疗产生深远影响。

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).