Aleksandra Olszewska: Manufacture and Initial Characterisation of RAPIDTM Biodynamic Haematogel, an Autologous Platelet and Leukocyte-Rich Plasma Gel for Diabetic Foot Ulcers

1.1. Healthcare Burden of Diabetic Foot Ulcers

Diabetes is surging, and it is predicted that there will be between 1.22 and 1.39 billion diabetic patients globally by 2050 [1]. The lifetime risk of developing a diabetic foot ulcer (DFU) is 19–34% [2]. DFU is a life-altering or even life-threatening condition closely linked to other diabetes complications including neuropathy and vascular disease. The ulcer itself often originates from trauma to the foot, combined with insensitivity to pain, poor circulation and impaired healing processes in patients with diabetes, resulting in a hard-to-heal ulcer. Not only do DFUs significantly elevate mortality rate (2.48 times higher for diabetic patients with DFUs than without) [3], they also place an immense burden on global healthcare systems. The United Kingdom National Health Service spending on wound management was GBP 8.3 billion in 2017/2018, with GBP 5.6 billion directed towards unhealed wounds. Notably, 85% of unhealed wound costs were incurred in the community setting, of which only 6% was allocated to wound care products [4]. In the US, where an estimated 11.3% of the population lives with diabetes [5], DFUs were the second highest expense in wound care (after surgical wounds) reaching USD 9–13 billion in 2018 [6]. Pakistan, a country that in 2021 had the highest prevalence of diabetes worldwide (26.7%) [7], reports a pooled DFU prevalence of between 12–16% [8]. While no specific DFU-associated costs have been published, Pakistan experiences a significant economic burden of diabetes-associated treatments, reaching over USD 24 billion annually [9], and these numbers might underestimate the real costs as limited data are available.

1.2. Need for More Effective Treatments

The treatment and management of DFUs are challenging; the recurrence rate is 40% within the first year and as high as 65% within five years of the DFU healing [2]. Current management strategies revolve around multidisciplinary care in foot clinics, with podiatrists, nurses and vascular surgeons focusing on offloading, wound debridement, infection and pain management, and frequent dressing changes [10]. In severe cases, vascular reconstruction may be required or, in the absence of healing, amputation—an option associated with an almost 70% mortality rate for diabetic amputees within five years [2]. In an effort to develop more effective DFU treatments, the scientific and wider medical community is developing novel treatments, including advanced dressings and negative pressure therapy, as well as more personalised cellular therapies, e.g., stem cell, growth factor and platelet/fibrin-based therapies [11,12].

1.3. RAPID Gel as a Point-of-Care Therapeutic Product

Platelet-rich plasma (PRP) is a concentration of blood platelets which contains granules, the contents of which are associated with proliferative and potential wound healing benefits. Several growth factors found in PRP have been previously associated with tissue proliferation and wound healing. These include, but are not limited to, platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) [13]. PRP can be generated from patient’s own blood and has potential as a regenerative therapy. It has been applied across many medical fields with mixed outcomes in terms of success, which has been attributed to poorly controlled preparation methods and lack of standardization. There have been relatively few large-cohort randomized controlled clinical trials (RCTs) [14,15]. Encouragingly, recent studies of PRP therapies for DFU have shown promising outcomes [16], despite utilising varying amounts of starting material, as well as different preparation methods, dosage forms, administration methods and frequencies.

RAPID Biodynamic Haematogel is an autologous leukocyte and platelet-rich plasma product that has been developed by Biotherapy Services. It is prepared using a point-of-care (POC) manufacturing process which enables doctors or healthcare professionals to manufacture the RAPID gel at a patient’s bedside. It has been developed through pilot studies and clinical trials in patients with DFU and has shown promising clinical outcomes [17]. As an autologous product, the safety concerns associated with blood and other biologically-derived products are avoided. POC manufacturing allows RAPID gel to be produced locally in clinical and home settings.

1.4. Challenges Associated with RAPID Gel

As a POC-manufactured autologous product, PRP offers benefits like ease of preparation and personalisation but also presents challenges. Variability in autologous products, such as growth factor content, is inevitable, and implementing stringent acceptance criteria for suitability of the blood used for product manufacture is impracticable. Rather, assurance of product quality can be achieved by control of the manufacturing process and definition of critical product attributes. Novel therapeutic PRP-based therapies such as RAPID gel are not currently recommended by the NHS, mostly due to a need for more comprehensive studies to establish benefit-to-cost margins [18,19]. Worldwide, these therapies are available for multiple conditions but are often ineligible for insurance coverage or only accessible as part of ongoing clinical trials [20]. Regulatory inconsistencies across countries further complicate issues like product standardization and best practices.

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