Using extracellular calcium concentration and electric pulse conditions to tune platelet-rich plasma growth factor release and clotting

Abstract

Platelet-rich plasma (PRP) is an emerging autologous biologic method for wound healing. Clinicians apply PRP either topically (where it is activated ex-vivo before treatment by adding an external agent to trigger clotting and the release of growth factors that facilitate wound healing) or through injection (where it is activated in vivo at the injury site with no prior activation before injection). Because topical PRP activation typically utilizes bovine thrombin, which has significant potential side effects and high costs, recent studies have assessed the efficacy of combining extracellular calcium (EC) and electric pulses (EPs) to activate PRP. The potential to apply this novel technique to PRP both topically and internally via injection raises the question about the ability to tune the clotting time and growth factor release for a given application. While previous studies have assessed the impact of applying EPs of various durations either directly (conductive coupling) or indirectly (capacitive coupling) to PRP containing EC, no studies have assessed the tunability of this activation based on modifying EP parameters, EP delivery method (conductive or capacitive coupling), and the EC concentration. We hypothesize that tuning these parameters will modify intracellular calcium uptake to permit the control of growth factor release and clotting time, which are critical for optimizing PRP for either topical or internal clinical applications. A pilot study for a single donor demonstrates the potential for tunability as a function of the intensity of membrane manipulation and calcium concentration, which facilitate the increase of cytosolic calcium. This motivates future studies assessing EC and EP optimization and in vivo studies to determine the overall efficacy of this tunability for wound healing.