A new absorbable antimicrobial bone graft substitute

一种新型可吸收抗菌骨移植替代品

• 批准号: 6992567
• 负责人: DAVID P MARTIN
• 金额: $ 10万
• 依托单位: TEPHA, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6992567
• 关键词: antiinfective agents; antiseptic sterilization; biological models; biomaterial development /preparation; biomaterial interface interaction; biomechanics; bone; cytotoxicity; drug delivery systems; gentamicins; laboratory rabbit; model design /development; osteomyelitis; polymers; spectrometry; surface coating; tissue /cell culture

DESCRIPTION (provided by applicant): The objective of this research is to determine the feasibility of developing an absorbable antimicrobial bone graft substitute for the treatment of osteomyelitis. Osteomyelitis occurs in an estimated 1-3% of all orthopedic surgeries with the incidence being even higher in spinal fusion and open fractures. Despite this rate of infection, there is currently no FDA approved implantable antibiotic loaded bone grafting material for the treatment and prevention of osteomyelitis. The research approach will employ a new absorbable biomaterial, known as TephaFLEX(tm) polymer, that offers a new set of properties for developing a suitable implantable drug delivery device for the treatment of osteomyelitis. In preliminary studies, it has been demonstrated that the TephaFLEX(tm) polymer can be loaded with a high percentage of a model antibiotic, and deliver this drug in vitro over a prolonged period that is potentially required for the treatment of osteomyelitis. The specific aims of this project are to: (1) Prepare antimicrobial drug release matrices from the TephaFLEX(tm) polymer and gentamicin that can be combined with existing bone graft materials, (2) Identify conditions to sterilize the TephaFLEX-gentimicin devices, (3) Identify suitable formulations of gentamicin loaded TephaFLEX(tm) bone graft substitutes and matrices that provide prolonged release of the antibiotic at therapeutic levels, (4) Confirm that gentamicin retains antibiotic activity after release and determine the Minimal Inhibitory Concentrations (MIC) of the sterilized bone graft substitutes and matrices against select target bacteria, (5) Confirm that the TephaFLEX(tm) devices lack cytotoxicity (i.e. grade <2) in an animal cell culture model for cell viability, and (6) Establish an animal model for infection that can be used to confirm the suitability of the TephaFLEX(tm) polymer for bone grafting, and also for Phase II in vivo studies of efficacy. In addition to developing a new product for the treatment of osteomyelitis, the research will also help to introduce a new absorbable medical biomaterial into the medical community that could be used in other drug delivery and medical device applications. Preliminary results using tetracycline and gentamycin release confirmed a linear release of antibiotic over a period typical for a course of antibiotic. Proposed experiments will employ bone matrix studies to demonstrate the dual utility of this polymeric composition.

描述（由申请人提供）：本研究的目的是确定开发可吸收抗菌骨移植替代物治疗骨髓炎的可行性。骨髓炎发生在所有骨科手术的估计1-3%，脊柱融合术和开放性骨折的发病率甚至更高。尽管有这种感染率，但目前还没有FDA批准的用于治疗和预防骨髓炎的可植入抗生素负载的骨移植材料。该研究方法将采用一种新的可吸收生物材料，称为TephaFLEX（TM）聚合物，为开发用于治疗骨髓炎的合适的植入式药物输送装置提供了一套新的特性。在初步研究中，已经证明TephaFLEX（tm）聚合物可以装载高百分比的模型抗生素，并且在体外长时间递送这种药物，这是治疗骨髓炎潜在需要的。该项目的具体目标是：（1）由TephaFLEX TM聚合物和庆大霉素制备抗微生物药物释放基质，其可以与现有的骨移植材料组合，（2）确定对TephaFLEX-庆大霉素装置进行灭菌的条件，（3）确定负载庆大霉素的TephaFLEX TM骨移植替代物和基质的合适配方，其提供治疗水平的抗生素的延长释放，（4）确认庆大霉素在释放后保留抗生素活性，并确定灭菌骨移植替代物和基质对选定目标细菌的最小抑制浓度（MIC），（5）确认TephaFLEX（tm）器械无细胞毒性（即<2级）的细胞活力，和（6）建立感染的动物模型，该模型可用于确认TephaFLEX（TM）聚合物对于骨移植的适用性，也可用于II期体内功效研究。除了开发用于治疗骨髓炎的新产品外，该研究还将有助于向医学界介绍一种新的可吸收医用生物材料，可用于其他药物输送和医疗器械应用。 使用四环素和庆大霉素释放的初步结果证实了抗生素在抗生素疗程的典型时间内的线性释放。 提出的实验将采用骨基质研究来证明这种聚合物组合物的双重效用。