Calcium phosphate processing strategies for the delivery of therapeutic agents

再生因疾病或创伤而丢失的骨骼可能是一项重大挑战。慢性骨感染仅是导致显著骨损失的衰弱性疾病的一个实例，所述显著骨损失即使通过局部干预也难以消除，并且对患病部位处的组织或相关关节功能的恢复构成威胁。磷酸钙多年来被认为是良好的骨移植材料，因为已知它们在植入骨缺损中时促进新骨生长。然而，加工限制通常限制了它们在药物递送应用中的使用。该计划旨在通过新的加工方法开发一类可降解的磷酸钙（多磷酸钙）作为临时基质，用于主动引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。这将通过药物或治疗剂的策略性掺入和局部释放来实现。该提案建立在先前开发的载药磷酸钙的基础上，并特别关注这些可降解基质递送大分子（蛋白质）的能力。通过加工操作以磷酸钙-银复合系统的形式产生具有潜在广泛适用性的创新抗菌磷酸钙是这项工作的另一个重点，因为这是增强这些基质在自固化磷酸钙骨水泥中的功能性用途。重要的是，这里正在开发的方法可能有助于提高需要这种手术干预的加拿大人的生活质量，同时通过降低与多次手术相关的成本来减轻负担过重的医疗保健系统的压力。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产生深远的影响（例如，牙齿周围的牙周组织）和其他使人衰弱的骨疾病如癌症（骨肉瘤）的有效治疗。

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).