Processing of calcium phosphate - functional peptide composites for orthopaedic applications

随着人口老龄化，对生物材料和生物医学设备的需求不断增加，以取代或恢复组织功能。仅在骨科领域，加拿大每年就有超过10万个人工髋关节和膝关节被植入。假体关节感染是骨科手术的主要并发症。关节置换手术的总感染率为0.5%-5%，感染也约占总植入失败的18%。植入物感染给患者和医疗系统带来了严重的后果，包括大幅延长住院时间，增加翻修手术次数，显著增加医疗费用，并增加死亡率。局部应用传统抗生素可预防细菌粘连和种植体周围感染。然而，使用万古霉素等传统抗生素进行局部给药的一个严重问题是耐药病原体的发展和传播。这种抗生素耐药性可能会造成毁灭性的影响，并已成为一个严重的公共卫生问题。 这项建议旨在开发新的生物材料技术，以解决骨科设备中的一个关键挑战：预防设备相关感染，同时实现早期骨整合。我们已经确定了应对挑战所必需的两种主要成分：用于促进骨愈合的磷酸钙生物陶瓷和不会产生抗生素耐药性的抗菌肽。我们建议开展系统的基础性研究，以开发磷酸钙-抗菌肽复合材料。我们的第一个目标是研究磷酸钙和抗菌肽之间的相互作用，以实现多肽的可控递送。第二个目标是开发复合材料作为植入材料的涂层。长期目标是开发新一代骨科植入物，并建立持续的生物材料研究和培训计划。这项研究将带来新的生物医学技术，使加拿大生物医学行业具有竞争力，为医疗专业人员抗击设备感染带来新的解决方案，并改善加拿大人的医疗保健和生活质量。

With an aging population, there are increasing demands for biomaterials and biomedical devices to replace or restore tissue functions. In orthopaedics alone, more than 100,000 artificial hip and knee joints in Canada are implanted every year. Prosthetic joint infections are major complications in orthopaedic surgery. The overall infection rate is 0.5-5% for joint replacement surgery and infection also accounts for about 18% of the total implant failure. Implant infection brings severe consequences to the patients and the health care system, including substantially prolonged hospitalization, increased number of revision surgery, significant increase in healthcare costs, and increased mortality rate. Local delivery of traditional antibiotics could prevent bacteria adhesion and peri-implant infection. However, a serious concern over using traditional antibiotics such as vancomycin for local delivery is the development and spreading of antibiotic resistant pathogens. Such antibiotic resistance can lead to devastating effects and has become a serious public health problem. This proposal is aimed at developing novel biomaterial technologies to address a key challenge in orthopaedic devices: preventing device associated infections, and at same time achieving early bone integration. We have identified two leading components essential to address the challenge: calcium phosphate bioceramics for promoting bone healing and antimicrobial peptides that do not develop antibiotic resistance. We propose to carry out systematic and fundamental studies to develop calcium phosphate-antimicrobial peptide composites. Our first objective is to investigate the interactions between calcium phosphates and the antimicrobial peptides in order to achieve controlled peptide delivery. The second objective is to develop the composites as coatings on implant materials. The long-term objectives are to develop a new generation of orthopaedic implants and to build sustained biomaterials research and training program. This research will lead to new biomedical technologies that will enable Canadian biomedical industry to be competitive, bring new solution to medical professionals in combating device infections, and improve the health care and quality of life of Canadians.