An antimicrobial-eluting bioresorbable bone filler for orthopaedic application

用于骨科应用的抗菌洗脱生物可吸收骨填充剂

• 批准号: 8712646
• 负责人: JASON D SMITH
• 金额: $ 15.66万
• 依托单位: CARMELL THERAPEUTICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8712646
• 关键词: Address; Adjuvant; Animals; Antibiotic Therapy; Antibiotics; Antimicrobial Effect; Bacteria; Bacterial Infections; Biocompatible Materials; Biological Assay; Biological Products; Blood Platelets; Bone Growth; Bone Regeneration; Cell Culture Techniques; Clinical; Clinical Research; Data; Debridement; Defect; Deoxyribonuclease I; Development; Diffusion; Documentation; Electron Microscopy; Excision; Facilities and Administrative Costs; Feasibility Studies; Filler; Fluorescence; Fracture; Fracture Healing; Gentamicins; Goals; Growth Factor; Human; In Vitro; Infection; Infection Control; Injury; Kinetics; Knowledge; Label; Lead; Licensing; Limb structure; Marketing; Metabolic; Microbial Biofilms; Modeling; Open Fractures; Operative Surgical Procedures; Orthopedics; Osteoblasts; Osteomyelitis; Outcome; Patients; Phase; Plasma; Polymethyl Methacrylate; Prevalence; Price; Procedures; Productivity; Proteins; Pseudomonas aeruginosa; Rattus; Recruitment Activity; Risk; Safety; Side; Site; Small Business Innovation Research Grant; Staging; Staining method; Stains; Staphylococcus aureus; Technology; Testing; Therapeutic; Time; Treatment Cost; Validation; Wages; Work; Workers' Compensation; antimicrobial; antimicrobial drug; bacterial resistance; base; biodegradable product; biomaterial compatibility; bone; bone healing; cold temperature; cost; cost effective; cytotoxic; design; drug resistant bacteria; improved; in vitro Assay; in vitro activity; in vivo; man; manufacturing process; meetings; open wound; prophylactic; public health relevance; regenerative; repaired; standard of care; technological innovation; tibia; tissue repair

DESCRIPTION (provided by applicant): The long-term goal of Carmell Therapeutics for this proposal is to develop a blood plasma-based biomaterial bone filler product that will elute antimicrobials to inhibit infection. Bacterial contamination is present perioperatively in 48-68% o all open wounds and 100% of severe open injuries. Per year in the U.S. ~ 123,000 open tibia fractures are contaminated, requiring an added patient treatment cost of $29,000. Additional indirect costs (Worker's Compensation, lost wages, productivity, etc.) are enormous but harder to quantify. Current standard of care involves systemic antibiotics, early debridement, and the off-label, prophylactic use of local antibiotic delivery via impregnated poly(methyl methacrylate) (PMMA) beads, which have unknown release kinetics and must be removed from the defect prior to bone reduction procedures. Clinicians need a product that enhances bone repair as well as controls infection through local antibiotic delivery. Carmell believes that combining antimicrobial delivery with its blood plasma-based biomaterials (PBMs) (which elute regenerative factors as they degrade) have the potential to meet this need. The Phase I hypothesis is that the product, the REPAIR Plus" Bone Putty, can locally deliver antimicrobials to control infection. To test the hypothesis antimicrobials will be incorporated into PBMs and their release and activity will be verified using disk diffusion-based in vitro assays. The products biological activity and biocompatibility will then be established in vitro using a metabolic assay and electron microscopy. The product's antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus and their biofilms will be demonstrated in vitro using 3D fluorescence staining and cell culture techniques. Finally, clearance of S. aureus infection in vivo in a pilot feasibility study using a rat tibia model will be established, where bacteria added to a bone defect will be challenged with the product to determine the product's ability to clear the bacteria over 14 days. Following the demonstration of feasibility in Phase I, Phase II will build on the infection control data to examine enhanced bone repair (with infection control) in vivo as well as conduct regulatory-focused studies to demonstrate biocompatibility and safety, all to prepare for a first-in-man clinical study. Carmell will additionally recruit an antibiotic supplier as a partner for supply and regulatory documentation as well as for potential licensing opportunities. Overall, an effective, off-the-shelf, and easy to use product that could improve patient outcome and reduce treatment complications as well as costs will have enormous marketing potential for the treatment of open tibia fractures and other open bone fracture applications.

描述（由申请人提供）：Carmell Therapeutics针对该提案的长期目标是开发基于血浆的生物材料填充产物，该产品将洗脱抗菌剂以抑制感染。细菌污染在48-68％o所有开放性伤口和100％严重开放损伤中存在。美国每年约有123,000个开放性胫骨骨折被污染，需要增加29,000美元的患者治疗费用。额外的间接费用（工人补偿，工资损失，生产力等）是巨大的，但很难量化。当前的护理标准涉及系统性抗生素，早期清创术和标签外，预防性使用局部抗生素通过浸渍的聚（甲基丙烯酸甲酯）（PMMA）珠的递送，这些珠子必须将释放动力学释放不明，并且必须从骨还原之前的缺陷中删除。临床医生需要一种通过局部抗生素递送来增强骨修复和控制感染的产品。卡梅尔认为，将抗微生物递送与血浆基于血浆的生物材料（PBMS）（降解后的再生因素）相结合有可能满足这种需求。第一阶段的假设是，维修和“骨腻子，可以在局部传递抗菌剂以控制感染。要测试该假说的抗菌剂将被纳入PBMS中，并将使用基于磁盘扩散的易生物学分析来验证其释放和活性。然后，使用基于磁盘的生物学效应。针对铜绿假单胞菌和金黄色葡萄球菌及其生物膜的抗菌活性将使用3D荧光染色和细胞培养技术在体外证明，最终将在添加的小鼠模型中添加的aureus s. aureus Incortions中清除。 对于骨缺陷而言，该产品将受到挑战，以确定产品在14天内清除细菌的能力。在I阶段的可行性证明后，II期将基于感染控制数据，以检查体内增强的骨修复（感染控制）以及进行调节的研究以证明生物相容性和安全性，所有这些都为第一名人体临床研究做准备。卡梅尔还将招募抗生素供应商作为供应和监管文件的合作伙伴以及潜在的许可机会。总体而言，这是一种有效的，现成的，易于使用的产品，可以改善患者结果并减少治疗并发症以及成本将具有巨大的营销潜力，以治疗开放性胫骨骨折和其他开放性骨折应用。