Poster J2 - Autologous Blood Clots: A Novel Approach for Antibiotic Delivery

Thursday, October 24, 2024

10:00 AM - 11:00 AM EST

Location: Exhibit Hall E, F & G

Primary Investigator(s)

Jennifer C. Ku, BS

Medical Student
Homer Stryker MD School of Medicine, United States

Co-Author(s)

HP

Haiying Pan, n/a

Manager
Homer Stryker MD School of Medicine (WMed), United States
David M. Richter

Medical Student
Homer Stryker MD School of Medicine (WMed), United States
GA

Genevieve Abe, n/a

Postdoc fellow
WMed, United States
RS

Robert Sawyer

Professor and Dean
Homer Stryker MD School of Medicine (WMed), United States

Presenting Author(s)

YL

Yong Li

Professor
Homer Stryker MD School of Medicine (WMed)
Kalamazoo, Michigan, United States

Introduction: Natural biomaterials designed for drug delivery hold significant potential in wound healing; however, a biocompatible, adaptable, and cost-efficient delivery system has yet to be developed. Furthermore, current therapies often require oversight of the U.S. Food and Drug Administration, presenting a challenge for widespread clinical adoption. Autologous blood clots (BC) emerge as a compelling contender in the realm of orthobiologics, owing to the intrinsic capacity of BC to function as natural reservoirs for controlled release of growth factors (GF) in conjunction with the fibrin matrix inherent to the BC structure1. The aim of this study was to assess the duration of sustained antibiotic release from BC and their potential impact on host mesenchymal stem cells (MSC). Additionally, this investigation explored the use of autologous BC composited with antibiotics and mesenchymal stem cells (MSC) as a strategic methodology to treat a comprehensive spectrum of wounds and orthopedic injuries. We hypothesize that the integration of autologous BC with antibiotics and MSC will function as a pro-regenerative delivery vehicle capable of sustained release of therapeutic factors to effectively treat and prevent infections.

Materials and

Methods: Porcine and murine blood samples were allowed to clot at room temperature to form BC in vitro. BC were composited with vancomycin and gentamicin at concentrations up to 5.0 mg/mL, with antibiotics and bone marrow derived MSC at a concentration of 1 x 106 cells/mL, or with PBS. Composited BC were evaluated for antibiotic release and antimicrobial activity for a duration of one week. The release of GF, such as vascular endothelial growth factor (VEGF), from composite BC was assessed at daily intervals over a duration of 7 days and quantified by sandwich ELISA assays (DuoSet ELISA for Mouse, R&D Systems).

Results, Conclusions, and Discussions:

Results: The findings suggest vancomycin and gentamicin do not exhibit noticeable toxicity on porcine and murine MSC over the span of one week when composited with BC. Notably, composite BC demonstrated a controlled and sustained release of antibiotics over the 7-day period (Figure 1). Moreover, the composited BC with antibiotics indicated the functional capability to inhibit bacterial proliferation for a duration of 7 days (Figure 2). The composite BC combined with MSC also displayed a sustained and prolonged release of GF, such as VEGF, for a period exceeding 7 days in vitro with a concentration diffusion range of 220-350 pg/mL.

Discussion: Our results indicate autologous BC serve as efficient therapeutic carriers for sustained antibiotic release. BC composited with antibiotics effectively inhibited bacterial proliferation for a 7-day period, providing a clinically relevant timeframe for wound healing and infection treatment and prevention. Furthermore, when combined with MSC, the composite BC exhibited notable levels of VEGF release, a concentration level sufficient to promote angiogenesis in wounds. The clinical translational potential of this approach holds significant promise. The straightforward methodology, coupled with the inherent capacity for GF release and antibiotic delivery, positions BC as a versatile and natural biomaterial with multifaceted roles in regenerative medicine. Their dual role as a reservoir for therapeutic factors and a biomaterial to treat and prevent infection underscores their efficacy in addressing a wide array of wounds and orthopedic injuries. This simple BC composite system offers several advantages including minimal risk, simple use, and cost-effective approach. Utilizing BC as biomaterials could present a transformative shift in treatments, offering an innovative and clinically impactful solution for broad integration into clinical practice.
SIGNIFICANCE/CLINICAL RELEVANCE: This study highlights autologous BC as a viable delivery system for wound healing and regeneration, efficiently delivering antibiotics and potentially other therapeutic agents to treat and prevent infections, while accelerating the wound healing process. This approach holds significant potential for advancing wound care strategies.

Acknowledgements (Optional):