Smith, Oliver John; (2021) Platelet rich plasma and its role as a therapy for wound healing. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Chronic wounds are a significant global health burden. They reduce a patient’s quality of life, carry a high risk of infection and cause considerable morbidity. Despite costing the NHS £5 billion per year, current treatment options have limited efficacy. Numerous reports suggest that platelet rich plasma (PRP) can promote wound regeneration through the release of growth factors (GF). Release of microbicidal peptides may also encourage healing through reducing the growth of common wound bacteria. The clinical evidence for PRP is, however, limited due to low quality studies, poor reporting of methodological and outcome data, and widespread variation in preparation technique. A huge number of commercial PRP devices exist, which produce PRP with different compositions and preparation techniques. Little evidence exists on the effect of activation of PRP on GF production, antimicrobial activity or how PRP affects biofilm growth. This thesis aims to determine the strength of evidence to support the use of PRP for wounds, together with providing experimental data on: 1) the effect of PRP preparation method on growth factor production, 2) the antimicrobial effect of PRP, and 3) a clinical study investigating PRP with fat grafting in diabetic wound repair. Part A of the thesis investigated a single PRP harvesting system. We altered the composition of its PRP in six different ways to assess how this affects GF production. We found that the mode of platelet activation did not significantly effect GF (VEGF, PDGF, IGF) release when compared with non-activated PRP. Vitamin C, however, significantly reduced GF production (P<0.05). We also found that PRP, regardless of activation status, was bacteriostatic against free-floating and simple colonies of S.aureus and S.epidermidis. There was no benefit, however, of PRP against more complex biofilm colonies. Part B of the thesis investigated PRP in clinical combination with autologous fat grafting (AFG), a procedure becoming more common in wound therapy. Studies have shown combining AFG with PRP may enhance the regenerative capacity of both and increase the survival of fat grafts. Through three systematic reviews, this thesis demonstrated there is no clear clinical evidence that AFG-PRP is better than AFG alone. These reviews highlighted a need for high level evidence, and a feasibility randomised controlled trial (RCT) was undertaken to evaluate AFG and AFG-PRP in diabetic wounds. Patient engagement with the interventions was excellent but recruitment was low, with only 60% (n=18) of the target achieved. This RCT produced data to power a multi-centre trial, identified key barriers to recruitment and gave recommendations to improve trial methodology. Due to low numbers, clinical efficacy was not tested, but there was no clear benefit to either AFG or AFG-PRP. Histological analysis of wound biopsies taken during the trial suggested there may be a benefit to AFG and AFG-PRP treatment by promoting angiogenesis of the wound bed. This thesis has provided important data on the use of PRP in wound regeneration which will help guide clinical practice and future research in these emerging therapies.

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