Biologically-informed development of autologous platelet-based wound healing gels

RAPID Biodynamic Haematogel is an investigational medicinal product in phase 2b clinical trials to establish its efficacy in treating diabetic foot ulcers. This platelet rich plasma (PRP) gel is manufactured at the point of care, applied directly onto the wound and occluded for a period of up to one week. Although the exact mechanism behind the therapeutic effect is not fully characterized, it is thought that the liquid exudate from the gel contains growth factors (e.g. vascular endothelial growth factor, insulin-like growth factor 1, platelet-derived growth factor) and cytokines which are stored in the secretory a-granules in platelets. These factors stimulate fibroblast proliferation, angiogenesis and collagen synthesis, thus accelerating the process of wound healing. Clinical case studies verify that this is a life-changing advanced therapy that has been fast-tracked to the clinic for patients with diabetic ulcers that are unresponsive to other therapies. However, there are significant industrial and regulatory challenges to overcome to realise the full potential of platelet-based medicines and make them more widely available. A sound scientific understanding of the therapy is key to optimising therapeutic efficacy, ensuring patient safety and assuring medicinal product quality by enabling evidence-guided product development and regulation.
Rationale for the project
Platelet-based medicines are in their infancy and little is known about their precise mechanism of action. Nonetheless, PRP therapy has captured the imagination of clinicians and patients such that adoption into clinical practice has preceded the basic science underpinning the therapy. The active ingredient(s) and corresponding metabolic functions of PRP gels are not definitively established and variation in patient haematology means that the chemical and biologic constituents of a PRP product will vary considerably from gel to gel. For example, platelets from elderly or acutely traumatised patients may have diminished healing properties. In this respect, PRP gels are unlike drug molecules or conventional medicinal products and the substantial degree of gel-to-gel variation would breach normal regulatory requirements for consistency.
The project will be driven by two hypotheses: (i) the methodology for preparing PRP gels is variable - this may contribute to inconsistent or suboptimal clinical outcomes, (ii) physicochemical properties and biomarkers in the secretome can identified as indicators of product quality. Defining quality attributes will enable control of PRP gel manufacturing by specification-setting for the process and product.
Aim and objectives
The project aims to provide insights into the mechanism of action underpinning PRP gel efficacy and link this to the manufacturing process and critical product attributes. This will enable evidence-based specification-setting and quality control to assure PRP product quality when utilised in clinical settings. Specific objectives are:
1. Optimise PRP-gel formation in terms of process parameters and identify critical product attributes
2. Determine biological features and chemical signatures indicative of wound healing activity
3. Investigate the wound healing effect in an in vivo model