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Biomaterials

Biomaterials - Poster Session D

Poster B10 - Patient Specific Fibrin-Based Nanoparticles for Treatment of Equine Lower Limb Wounds

Friday, October 25, 2024
3:30 PM - 4:30 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Horses commonly incur lower limb injuries, which can result in costly treatments for horse owners. These chronic non-healing wounds present a challenge within veterinary medicine due to tissue loss and infection, eventually leading to longer recovery times. Lower limb wounds typically result in a prolonged inflammatory response with delayed epithelialization leading to a higher occurrence of proliferative granulation tissue. Current treatments for distal limb wounds include medications, bandages, and topical therapies but have limited success. The Brown Lab has developed fibrin-based nanoparticles (FBNs), which are pre-polymerized nano-scale particles with physiologically relevant concentrations of fibrinogen and thrombin. Previous studies have shown that FBNs stimulate clot formation at the wound site to support wound healing and increase healing speed.

Materials and

Methods:  We have focused on the development of patient-specific FBNs for treating horse distal limb wounds by reducing healing time and decreasing scar tissue. Equine platelet-poor plasma FBNs (pFBNs) are an alternative FBN formulation developed as a patient specific therapeutic for horses. Equine platelet-poor plasma is combined with physiologically relevant concentrations of thrombin to form plasma clots, which are mechanically broken up into nanoparticles. The focus of this research is to analyze interactions between pFBNs when cocultured with equine fibroblasts for cell viability and morphology in vitro and ex vivo. Equine dermal fibroblasts (eDFs) are isolated from horse skin biopsies using collagenase. pFBNs were characterized by activated partial thromboplastin time (aPTT) tests, thin films, and spheroids with eDFs. pFBNs are also seeded into horse explants to form gels. Confocal microscopy was used to image pFBN clots.

Results, Conclusions, and Discussions: pFBNs were successfully synthesized to comparable sizes of the previously developed FBNs. Additionally, these particles were integrated into fibrin clots and increase overall fibrin density. pFBNs successfully gel when incorporated with fibrin, which allowed for seeding of eDFs. While no significant difference was seen in cell proliferation on pFBN thin films of differing concentrations (control: fibrinogen and thrombin clot, control + 0.5 mg/mL pFBN, control + 1 mg/mL pFBN), cells were viable on pFBN thin films. Additionally, a dose-dependent increase in clotting speed was seen via aPTT. pFBNs are both a useful and promising approach to scale up the production of FBNs because they provide nearly a 100x increase in yield compared to traditional FBNs. pFBNs provide an avenue for patient-specific treatments. Future studies include assessment of the mechanical properties of these particles, as well as additional 3D cell studies to assess cell proliferation and migration with the addition of pFBNs.

Acknowledgements (Optional):