A Platelet-Rich Plasma-Derived Biologic Clears Staphylococcus aureus Biofilms While Mitigating Cartilage Degeneration and Joint Inflammation in a Clinically Relevant Large Animal Infectious Arthritis Model

Abstract

The leading cause of treatment failure in Staphylococcus aureus infections is the development of biofilms. Biofilms are highly tolerant to conventional antibiotics which were developed against planktonic cells. Consequently, there is a lack of antibiofilm agents in the antibiotic development pipeline. To address this problem, we developed a platelet-rich plasma (PRP)-derived biologic, termed BIO-PLY (for the BIOactive fraction of Platelet-rich plasma LYsate) which has potent in vitro bactericidal activity against S. aureus synovial fluid free-floating biofilm aggregates. Additional in vitro studies using equine synoviocytes and chondrocytes showed that BIO-PLY protected these cells of the joint from inflammation. The goal of this study was to test BIO-PLY for in vivo efficacy using an equine model of infectious arthritis. We found that horses experimentally infected with S. aureus and subsequently treated with BIO-PLY combined with the antibiotic amikacin (AMK) had decreased bacterial concentrations within both synovial fluid and synovial tissue and exhibited lower systemic and local inflammatory scores compared to horses treated with AMK alone. Most importantly, AMK+BIO-PLY treatment reduced the loss of infection-associated cartilage proteoglycan content in articular cartilage and decreased synovial tissue fibrosis and inflammation. Our results demonstrate the in vivo efficacy of AMK+BIO-PLY and represents a new approach to restore and potentiate antimicrobial activity against synovial fluid biofilms.

TLR-activated mesenchymal stromal cell therapy and antibiotics to treat multi-drug resistant Staphylococcal septic arthritis in an equine model

“…Horses were enrolled in four cohorts (two/cohort) ( Figure 1 ). On day 0, intravenous jugular catheters were placed, and horses were inoculated intra-articularly in one randomly assigned tibiotarsal joint with 1×10 4 colony forming units (CFU) S. aureus [methicillin resistant S. aureus (MRSA) strain USA300] bacteria, as previously described ( 32 ). Horses then were treated on d1, 4, and 7 with either 20×10 6 pooled bone-marrow-derived allogeneic MSC and VAN (TLR-MSC-VAN) or VAN alone, with cell dose based on a previous report ( 33 ).…”

“…Qualitative bacterial sensitivity patterns were compared to that obtained initially for the injected bacteria. Quantitative bacterial cultures were performed of SF at d0, 1, 4, 7, 14 and of synovium at end-term as previously described ( 25 , 32 , 40 ). Briefly, to generate quantitative cultures, SF aliquots (250 µL) were centrifuged at 8,000 g for five minutes and supernatant was discarded.…”

“…Samples were processed for histologic examination with hematoxylin and eosin staining to assess for inflammatory changes. Samples were formalin fixed 48 h then decalcified in formic acid for 2 to 4 weeks, with solution changes every 3 d. Assessment of histology specimens were scored according to Osteoarthritis Research Society International (OARSI) and modified OARSI histology initiative for osteoarthritis in horses developed for septic arthritis ( 32 , 41 ).…”

Effect of BIO-PLYTM, a Platelet-Rich Plasma Derived Biologic on PRRSV-2-Infected Macrophages

“…Platelet rich plasma (PRP) is an autologous compound obtained from an individual's blood with numerous applications within the biomedical field [16][17][18][19][20][21][22][23][24]. Originally, PRP was found to be an effective treatment for musculoskeletal conditions such as osteoarthritis [25][26][27] or bone infections [28], among others [16][17][18][19][20][21][22][23][24]. As one of the main complications of traumatic lesions is potential subsequent bacterial infections [29][30][31], the discovery of the antimicrobial capacities of PRP brought great advantages to its utilization, since the application of a single compound could aid with multiple complications at a time such as pain relief [18], immune regulation [24] and bacterial control [27,[32][33][34][35].…”

“…Originally, PRP was found to be an effective treatment for musculoskeletal conditions such as osteoarthritis [25][26][27] or bone infections [28], among others [16][17][18][19][20][21][22][23][24]. As one of the main complications of traumatic lesions is potential subsequent bacterial infections [29][30][31], the discovery of the antimicrobial capacities of PRP brought great advantages to its utilization, since the application of a single compound could aid with multiple complications at a time such as pain relief [18], immune regulation [24] and bacterial control [27,[32][33][34][35]. Recently, the antiviral properties of PRP have been described for SARS-CoV-2 [36,37], leading the way for PRP and its derivatives to be applied as safe and effective antivirals.…”