Controlled delivery of platelet-derived proteins enhances porcine wound healing

Abstract

Platelet-rich plasma (PRP) is widely used for many clinical indications including wound healing due to the high concentrations of growth factors. However, the short half-life of these therapeutic proteins requires multiple large doses, and their efficacy is highly debated among clinicians. Here we report a method of protecting these proteins and releasing them in a controlled manner via a heparin-based coacervate delivery vehicle to improve wound healing in a porcine model. Platelet-derived proteins incorporated into the coacervate were protected and slowly released over 3 weeks in vitro. In a porcine model, PRP coacervate significantly accelerated the healing response over 10 days, in part by increasing the rate of wound reepithelialization by 35% compared to control. Additionally, PRP coacervate doubled the rate of wound contraction compared to all other treatments, including that of free PRP proteins. Wounds treated with PRP coacervate exhibited increased collagen alignment and an advanced state of vascularity compared to control treatments. These results suggest that this preparation of PRP accelerates healing of cutaneous wounds only as a controlled release formulation. The coacervate delivery vehicle is a simple and effective tool to improve the therapeutic efficacy of platelet-derived proteins for wound healing.

Inorganic Polyphosphates Are Important for Cell Survival and Motility of Human Skin Keratinocytes and Play a Role in Wound Healing

“…PRP and PRP with keratinocyte and fibroblast cells were shown to increase re-epithelialization at 7-14 days post-injury in mouse models, compared to non-treated controls [127]. In full thickness porcine wounds treated with the secreted proteins of PRP, wound re-epithelialization and collagen deposition were significantly increased in treated animals vs. saline controls [128]. Thus, PRP may improve wound healing in acute surgical wounds by secreting growth factors that support local microenvironments that promotes healing [129].…”

Persistent fibrosis and decreased cardiac function following cardiac injury in theCtenopharyngodon idella(grass carp)

“…The percentage of mature fibers in the injured region was used for statistical comparisons, although data for all defined colors are presented. Alignment was calculated as previously described (Long et al, 2017) using a fast Fourier transform (FFT) macro in ImageJ, where index values close to 1 indicate random fiber alignment and higher index values indicate increased fiber alignment.…”

Review: Multimodal bioactive material approaches for wound healing

“…30 This field, however, has faced challenges derived from the low stability of growth factors in an in vivo setting, a short half-life, and unwanted side effects as a result of immunogenicity of recombinant proteins. 16,37 As an alternative, growth factor gene delivery has seen an increase in popularity for its long shelf life and stability, in conjunction with low cost for manufacturing. The use of materials containing complementary DNA (cDNA) has led to an extended period of high growth factor concentration with more recognizable proteins in comparison to recombinant proteins.…”

“…40,41 An alternative to the external source of growth factors is to harvest a natural source of growth factors from platelet-rich-plasma (PRP) from the patient themselves or a healthy donor. 37,42 PRP is a rich source of growth factors and platelets which assist with clot formation and serve as a positive feedback for the release of a number of other factors necessary for wound healing. 43 PRP gel is produced using patient blood which has been centrifuged to separate the red blood cells from the PRP.…”