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Adipose tissue as a source of growth factors to promote wound healing: a human study of skin graft donor sites

Objective: In the microenvironment of wound sites, naturally occurring growth factors are crucial for cell migration, opsonisation, chemotaxis, differentiation and angiogenesis. Exogenous growth factors, such as platelet-rich plasma (PRP) and adipose tissue, also improve healing. Method: In the present within-subject study, we described the effects of PRP and adipose tissue extract (ATE) on skin graft donor site wound healing in patients requiring split-thickness skin grafts. Each patient, having at least two donor sites, received both control (no growth factor) and experimental (PRP or ATE) treatments. Wounds were evaluated on days 5, 7, 10, 15, 30 and 60. Digital photography and spectral images were used to analyse haemoglobin and melanin content, and re-epithelialisation area. Pain was assessed by visual analogue scale. Scar characteristics were scored on days 30 and 60. Biomaterial samples were analysed for growth factor and protein content. Results: The study included 24 patients (18 male and six female; mean age: 59.1 years). PRP was topically applied to wounds in 11 patients (13 donor sites) and ATE in 13 patients (15 sites). ATE-treated donor sites exhibited significantly accelerated wound re-epithelialisation on days 5 and 7 compared with control sites (p=0.003 and 0.04, respectively). PRP accelerated healing on day 7 compared with control sites (p=0.001). Additionally, the application of ATE improved scar quality on days 30 and 60 (p=0.0005 and 0.02, respectively). Pain scores did not differ significantly between treatments. Conclusion: In this study, both growth factor sources stimulated wound healing. ATE is an alternative source of growth factors that promote early wound healing and improve scar quality. Declaration of interest: This study was supported by the Finnish Technology and Innovation Agency TEKES, and Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital, Grant number 9S025. Patent issued in US, EPO, Brazil, India and pending in other countries. The authors have no conflict of interest to declare.

adipose tissue extract  ●  growth factors  ●  platelet-rich plasma  ●  skin graft donor sites  ●  wound  ●  wound care  ●  wound healing

In wound care management, a tailored and affordable treatment that provides an optimally vascularised microenvironment for wound healing is highly desirable.1,2 Open wounds are increasingly common in acute settings.2 It is estimated that 5–10% of open wounds become hard-to-heal and 6.5% develop an infection.3,4 Hard-to-heal wound treatment consumes a large proportion of healthcare budgets worldwide,3–5 making early and effective treatment crucial. Wounds are challenging to treat because there are multifactorial conditions related to the wound itself (aetiology, chronicity, depth, size, presence of infection), to the patient (comorbidities such as diabetes, vascular diseases and immunosuppressive states among others) and, finally, to the treatment that contributes to the healing outcome. This is why current wound healing research only scratches the surface of this vast and

Jenny F López,1,2 MD*; Antti Mikkola,2 MD; Jertta-Riina Sarkanen,1,3,4 PhD; Ilkka S Kaartinen,2,4 MD, PhD; Hannu O Kuokkanen,2,4 MD, PhD; Timo Ylikomi,1,3,4 MD, PhD *Corresponding author email: dra.jennylopez@gmail.com 1  Department of Cell Biology, School of Medicine (currently Faculty of Medicine and Health Technology), Tampere University, Tampere, Finland.  2  Department of Plastic Surgery, Unit of Musculoskeletal Diseases, Tampere University Hospital, Pirkanmaa Hospital District, Tampere, Finland.  3  FICAM, Finnish Centre for Alternative Methods, School of Medicine, University of Tampere, Tampere, Finland.  4  Science Center, Pirkanmaa Hospital District, Finland.

complex topic. Although there have been advances in modern dressings and biomaterials compared with previous decades, there is still a missing link, as no single treatment has been proved to provide optimal healing. Special attention has been focused on the mechanics of each biochemical phase of the coordinated wound healing process. Acute injury stimulates platelet aggregation, activation, and degranulation for the release of growth factors (GF), which are involved in cell migration, proliferation, differentiation, chemotaxis, angiogenesis and opsonisation.6,7 Both under- and over-production of GF may impair healing processes.8–10 Hard-to-heal wounds have deficits in GF and the application of exogenous GF improves healing in both chronic and acute clinical settings.9–14 Human plasma and adipose tissue are readily accessible sources of autologous GF.

A high concentration of platelets, up to nine times greater than plasma values, can be obtained through blood centrifugation. Various GF and cytokines can be measured in platelet-rich plasma (PRP), the most common of which are vascular endothelial GF (VEGF), platelet-derived GF, insulin-like GF-1 (IGF-1), hepatocyte GF, tumour necrosis factor alpha (TNF-α), transforming GF-beta (TGF-β), and interleukins (IL) 6 and 8.15–17 PRP is used extensively to promote hard and soft tissue healing. In vitro, PRP stimulates keratinocyte, fibroblast,

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JOURNAL OF WOUND CARE VOL 31, NO 4, APRIL 2022