PB0851 - Platelet secretion in wound healing: the essence of appropriate granule biogenesis

Background: Non-healing wounds cause a substantial global burden, both clinical and economic. Wound healing comprises multiple processes, e.g. haemostasis, inflammation, angiogenesis, and remodelling, in which different cell types are involved, including platelets, leukocytes, and endothelial cells. In various clinical and veterinary settings, platelet-rich plasma or growth factors are applied to the wound to accelerate wound repair processes. However, detailed functional knowledge of these applications is lacking, partially due to insufficient mechanistic insights about platelet activity in different wound healing phases.

Aims: We aim to investigate the role of the platelet’s secretory machinery in wound healing.

Methods: A 4-mm biopsy punch was used to make two symmetrical full-thickness circular excisions on the back of mice with defects in platelet granule biogenesis (Nbeal2-/- and Serglycin-/- mice) and wildtype mice (C57BL/6). Wounds were photographed and measured daily using callipers to determine percentage wound healing compared to baseline (day 0). Mice were sacrificed on day 3 and day 7, when blood was drawn and (partially healed) wounds were harvested with a 6-mm biopsy punch for further analyses.

Results: Nbeal2-/- mice showed severely impaired wound healing with distinctive wound morphology when compared to wildtype mice. Interestingly, and in contrast with Nbeal2 deficient mice, serglycin deficiency did not lead to altered wound healing, despite both Nbeal2 and serglycin playing important roles in platelet granule biogenesis and cargo packaging.

Conclusion(s): Until now, the role of platelets and their releasate in wound healing has not been investigated sufficiently. We are the first to specifically study platelet secretion in wound healing and ultimately provide a broader understanding of platelets in the complete wound healing process. Preliminary results suggest appropriate platelet granule biogenesis with sufficient granule cargo levels to be essential in skin wound healing. Additional analyses will have to elucidate more specific mechanisms.

This work is supported by the NIH/NHLBI (HL150818) and the VA.