Dottorato in TECNOLOGIE AVANZATE IN CHIRURGIA

Titolo della tesi: PrP: APPLICAZIONI E TECNICHE NELLE FERITE DI DIFFICILE GUARIGIONE

Chronic cutaneous ulcers present a significant medical challenge due to their high prevalence, limited prospects for complete healing with structural restoration, and the negative impact on patients’ quality of life. Furthermore, these lesions im- pose substantial costs on healthcare systems. To address this challenge, research is ongoing to identify therapies that can enhance tissue regeneration and reduce healing times. A promising approach is the use of blood-derived products, with a particular focus on Platelet-Rich Plasma (PRP). PRP, containing high concentrations of platelets, serves as a rich source of growth factors that can promote tissue healing. This study involved 42 patients with chronic cutaneous ulcers of various origins, excluding neoplastic ulcers where PRP is con- traindicated. The primary objective of this thesis was to assess whether the use of PRP could indeed offer advantages for tissue healing. Additionally, the study aimed to understand the added potential of this treatment in terms of reproducibil- ity, therapeutic effect, and costs compared to alternative therapies. Interest in PRP is steadily growing, as it represents a promising prospect for treating chronic ulcers and other skin lesions. Continued research in this field could lead to significant advancements in improving the quality of life for patients with chronic ulcers and reducing the economic burden on healthcare systems. Materials and Methods: For this study, 42 subjects (22 treated with PRP, 20 with standard dressings) suffering from chronic cutaneous ulcers of various etiologies, excluding neoplastic ul- cers, were recruited. Subjects ranged in age from 53 to 81 years and had ulcers that had not shown signs of healing for at least three months with conventional treat- ments. Patients with unstable hemodynamics due to ischemic heart disease, coagu- lation disorders, or those on anticoagulants and/or nonsteroidal anti-inflammatory drugs (NSAIDs) were excluded. Patients with platelet counts below 150*103/mm3, uncontrolled diabetes mellitus, the need for continuous oral corticosteroid therapy (>20 mg/day of prednisolone equivalent), a history of malignant tumors within 3 years, those who were or planned to become pregnant, and genuinely neoplastic ulcers were also excluded. Patients were treated between 2019 and 2023 with perilesional PRP injections at three-month intervals. Lesion dimensions were assessed at the study’s onset, and the Pressure Ulcer Scale for Healing (PUSH) was applied. Variations in these variables were recorded at 3 and 6 months following the last treatment. Data were 1 analyzed using the Mann-Whitney U test and Fisher’s exact test. Preparation of PRP: PRP was prepared using the Tube Method at the Plastic Surgery Department of the University of Campania ”Luigi Vanvitelli,” following institutional guidelines and ensuring asepsis. The procedure involved venous blood collection, gentle mixing to combine anticoagulant, and two centrifugation cycles. The final product, PRP, was drawn into 3 syringes, ready for infiltration with a 30-Gauge needle. The process yielded a final volume of approximately 3 mL with a platelet concentration doubled compared to whole blood. Results: The study included 21 female and 21 male patients aged between 53 and 81 years. Both gender and age were randomly distributed between the treatment and control groups (Fisher’s odds ratio: 1.466, p=0.38; Mann-Whitney U statis- tic: 179.5, p=0.312, respectively). At the beginning of treatment, the mean ulcer size in the treatment group was 2.14 cm in the major diameter (median 2 cm) and 2.24 cm (median 2 cm) in the control group (U=190.5, p=0.4644). Analyzing the rate of complete healing at 6 months, the PRP-treated group showed a 57% com- plete healing rate compared to 40% in the control group (Fisher’s odds ratio=3.98, p value=0.03), with a mean ulcer size of 3.5 mm in the treatment group and 6 mm in the control group (U=142.5, p value=0.018). The mean PUSH scale value at the study’s start was 0.9 (standard deviation=1.41) for the treatment group and 1.5 (standard deviation=1.24) for the control group. Patients’ response to treatment was monitored with weekly check-ups. Each visit followed the same procedure, including dressing removal, thorough disinfection and cleaning, debridement of the lesion, PRP application, and subsequent dressing. Conclusions: Chronic wounds, especially cutaneous ulcers, pose a significant challenge to the healthcare system and, most importantly, to patients. Regenerative medicine, par- ticularly PRP therapy, is showing increasingly promising results in this field. Its potential lies in minimally invasive approaches, clinical efficacy, product safety, cost- effectiveness, and ease of reproducibility. The aim of this observational study was to evaluate the current evidence re- garding the efficacy of platelet-rich plasma (PRP) concentrate in treating ulcers of various origins, such as venous, arterial, diabetic, pressure, and iatrogenic ulcers. Neoplastic ulcers were excluded due to concerns that PRP’s growth factors might promote tumor growth rather than lesion healing.