Trehalose lyophilized platelets for wound healing

Abstract

Fresh platelet preparations are utilized to treat a wide variety of wounds, although storage limitations and mixed results have hampered their clinical use. We hypothesized that concentrated lyophilized and reconstituted platelet preparations, preserved with trehalose, maintain and possibly enhance fresh platelets' ability to improve wound healing. We studied the ability of a single dose of trehalose lyophilized and reconstituted platelets to enhance wound healing when topically applied on full-thickness wounds in the genetically diabetic mouse. We compared these results with the application of multiple doses of fresh platelet preparations and trehalose lyophilized and reconstituted platelets as well as multiple doses of vascular endothelial growth factor (VEGF) and wounds left untreated. Trehalose lyophilized and reconstituted platelets, in single and multiple applications, multiple applications of fresh platelets and multiple applications of VEGF increased granulation tissue deposition, vascularity, and proliferation when compared with untreated wounds, as assessed by histology and immunohistochemistry. Wounds treated with multiple doses of VEGF and a single dose of freeze-dried platelets reached 90% closure faster than wounds left untreated. A single administration of trehalose lyophilized and reconstituted platelet preparations enhanced diabetic wound healing, therefore representing a promising strategy for the treatment of nonhealing wounds.

Incorporating Platelet-Rich Plasma into Electrospun Scaffolds for Tissue Engineering Applications

“…To date, the collection of whole blood and the concentration and isolation of platelets to make PRP has been proven effective in vitro for stimulating cellular activity in a number of formats, both in liquid 13,[33][34][35]37,[39][40][41] and in lyophilized PRGF form. [16][17][18][19] To the best of the authors' knowledge, this article serves as the first instance of a powdered PRGF being incorporated into an electrospun tissue engineering scaffold to serve as a controlled release vehicle for such a concentrated growth factor and cytokine milieu. While electrospun scaffolds have been used as growth factor delivery systems in the past, [42][43][44][45][46][47] they have typically been limited to the incorporation of only a small number of growth factors due in part to the cost associated with purchasing the recombinant or isolated proteins.…”

“…14 The use of freeze-dried PRP in a dermal wound has been shown to significantly increase cellular proliferation (up to 21 days), tissue regeneration, and angiogenesis in a mouse dermal wound. [16][17][18][19] Collectively, these studies demonstrate the importance of keeping PRPderived growth factors and cytokines in the wound site and slowly releasing them as the wound site becomes infiltrated with reparative cells.…”

“…Other techniques have been evaluated for further sustaining the release of growth factors from PRP and include the use of gelatin gel microspheres, 15 lyophilized PRP, [16][17][18][19] and alginate beads. 14 The injection of PRP gelatin gel microspheres in a mouse ischemic hind limb model demonstrated sustained release of the PRP potent angiogenic components as illustrated by an increase in perfusion, capillary density, and mature blood vessel density.…”

Tumors Stimulate Platelet Delivery of Angiogenic Factors in Vivo

“…1 Similarly, our previous work using recombinant growth factors or sonicated platelets on experimental full-thickness diabetic wounds revealed less of a pro-angiogenic effect than using intact platelets. 2,7 These data, therefore, suggest that the integrity of the platelet membranes or the open canallicular system may serve as the gateways controlling uptake and delivery of the various proteins that regulate angiogenesis.…”

“…One leading hypotheses is that angiogenesis relies on platelet delivery of regulatory proteins. Several angiogenesis regulating proteins that are carried by platelets are present at different times during wound healing, 2 and are stored in separate (pro-and anti-angiogenic) ␣-granule compartments in the platelet's cytoplasm. 3 Early evidence suggests that protease activated receptors may facilitate a selective release of pro-or anti-angiogenic factors from platelets.…”