A novel therapeutic for the treatment of biofilms in periprosthetic joint infections

项目摘要 据估计，到2030年，全关节置换术（TJA）手术将增加300%以上。假体周围 关节感染（PJI）是TJA后最严重的并发症，医疗费用超过16亿美元 每年。PJI的治疗通常需要手术干预结合长期化疗。 抗生素的费用为每个病人5万美元尽管这种积极的治疗，治疗只有一半是成功的， 患者PJI治疗失败的主要原因是保护性细菌生物膜的形成， 包在细胞外基质内的细菌群落，其耐受市售的 抗生素我们已经发现富血小板血浆（PRP）显示抗菌和抗菌膜 特性.然而，关于PRP临床疗效的文献存在巨大差异。到 为了克服这种变异性，我们开发了一种PRP衍生的生物制剂， 具有抗菌和抗炎活性，批次间差异很小或没有差异，称为BIO-BLOOD ™。在一匹马身上 在自体关节感染模型中，BIO-BLOOD ™不仅降低了关节内细菌负荷， 炎症和保护古老的软骨免受损伤。在这个提案中，我们将利用马 天然关节感染模型，以制造人类等效物并评价人类 使用已建立的PJI体外和体内模型，此提案的目标是生成密钥 决定是否将BIO-TECHNOLOGY ™推向II期临床前动物模型所需的数据，以及 向联邦药品管理局提交研究性新药（IND）申请。

PROJECT SUMMARY Total joint arthroplasty (TJA) procedures are estimated to rise by over 300% by the year 2030. Periprosthetic joint infection (PJI) is the most significant complication following TJA with healthcare costs exceeding $1.6 billion annually. Treatment of PJI generally requires surgical intervention combined with a prolonged course of antibiotics costing $50,000 per patient. Despite this aggressive treatment, treatment is only successful in half of patients. The leading cause of treatment failure in PJI is the formation of protective bacterial biofilms or communities of bacteria encased within an extracellular matrix which are tolerant to commercially available antibiotics. We have discovered that platelet-rich plasma (PRP) displays both antibacterial and antibiofilm properties. Nevertheless, there is tremendous variability in the literature on the clinical efficacy of PRP. To overcome this variability, we have developed a PRP-derived biologic that is specifically formulated with high antimicrobial and anti-inflammatory activity with little to no lot-to-lot variability, termed BIO-PLY™. In an equine model of native joint infection, BIO-PLY™ not only decreased intraarticular bacterial load but also dampened inflammation and protected venerable cartilage from damage. In this proposal, we will capitalize on the equine model of native joint infection to manufacture a human equivalent and evaluate the safety and efficacy of human BIO-PLY™ using established in vitro and in vivo models of PJI. The goal of this proposal is to generate the key data necessary for a go/no-go decision to advance BIO-PLY™ toward a Phase II pre-clinical animal model and an Investigational New Drug (IND) application with the Federal Drug Administration.