Immunoregulatory role of platelet derivatives in the macrophage-mediated immune response.

Background: Macrophages are innate immune cells that display remarkable phenotypic heterogeneity and functional plasticity. Due to their involvement in the pathogenesis of several human conditions, macrophages are considered to be an attractive therapeutic target. In line with this, platelet derivatives have been successfully applied in many medical fields and as active participants in innate immunity, cooperation between platelets and macrophages is essential. In this context, the aim of this review is to compile the current evidence regarding the effects of platelet derivatives on the phenotype and functions of macrophages to identify the advantages and shortcomings for feasible future clinical applications. Methods: A total of 669 articles were identified during the systematic literature search performed in PubMed and Web of Science databases. Results: A total of 27 articles met the inclusion criteria. Based on published findings, platelet derivatives may play an important role in inducing a dynamic M1/M2 balance and promoting a timely M1-M2 shift. However, the differences in procedures regarding platelet derivatives and macrophages polarization and the occasional lack of information, makes reproducibility and comparison of results extremely challenging. Furthermore, understanding the differences between human macrophages and those derived from animal models, and taking into account the peculiarities of tissue resident macrophages and their ontogeny seem essential for the design of new therapeutic strategies. Conclusion: Research on the combination of macrophages and platelet derivatives provides relevant information on the function and mechanisms of the immune response.

Efficacy of plasma rich in growth factors for healing chronic skin ulcers: a systematic review of randomized controlled trials with meta-analysis.

BACKGROUND: Chronic skin ulceration is a serious pathological condition for which the adjuvant use of platelet-rich plasma (PRP) has been indicated. However, evidence for the use of PRP in patients with chronic skin ulcers remains insufficient due to a large heterogeneity in experimental designs, PRP composition, and preparation protocols. OBJECTIVE: To assess previously published reports of the clinical effect of plasma rich in growth factors (PRGF) on chronic skin wounds. METHODS: A comprehensive search of the PubMed, Cochrane Library, and Scopus databases was performed to identify randomized controlled trials (RCTs) assessing the effect of PRGF on chronic ulcer healing, with no limitation regarding publication date (up to September 1, 2022). Percentage area reduction and probability of complete healing in chronic ulcers, pain reduction, infection risk, and cost savings were analyzed. A meta-analysis was performed, and the overall evidence was qualified using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: A total of 113 studies were identified. After full-text screening, 5 RCTs met the inclusion criteria. The meta-analysis showed a significant effect of PRGF on both wound area reduction (mean difference, 56.90% [95% CI, 52.28-61.51], I² = 0%; P = .56) and on the probability of complete healing (RR, 7.07 [95% CI, 1.84-27.16], I² = 0%; P = .53) in chronic ulcers. The overall risk of bias rating was "some concerns," whereas the certainty of evidence was high for both outcomes. A qualitative analysis suggested that PRGF did not increase infection risk and was able to reduce wound pain. CONCLUSION: The use of PRGF significantly enhances wound area reduction and also the probability of complete healing in chronic ulcers. More studies are needed to assess the effect of PRGF on pain and infection, as well as its cost-effectiveness.

Effect of Health Status and Heat-Induced Inactivation on the Proteomic Profile of Plasma Rich in Growth Factors Obtained from Donors with Chronic Inflammatory Skin Conditions.

Atopic dermatitis, psoriasis and lichen sclerosus are among the most challenging conditions treated by dermatologists worldwide, with potentially significant physical, social and psychological impacts. Emerging evidence suggests that autologous-platelet-rich plasma could be used to manage skin inflammation. However, the presence of soluble autoimmune components could hinder their therapeutic potential. The aim of this study was to analyze the proteomic profile of plasma rich in growth factors (PRGFs) obtained from donors with inflammatory skin conditions to evaluate the impact of skin health status on the composition and bioactivity of PRGF-based treatments. Venous blood from healthy volunteers and patients with psoriasis, lichen sclerosus and atopic dermatitis was processed to produce PRGF supernatant. Half of the samples were subjected to an additional thermal treatment (56 °C) to inactivate inflammatory and immune molecules. Proteomic analysis was performed to assess the protein profile of PRGFs from healthy and non-healthy patients and the effect of Immunosafe treatment. Differential abundance patterns of several proteins related to key biological processes have been identified, including complement activation, blood coagulation, and glycolysis- and gluconeogenesis-related genes. These results also demonstrate that the thermal treatment (Immunosafe) contributes to the inactivation of the complement system and, as a consequence, reduction in the immunogenic potential of PRGF products.

Improving the mechanical and biological functions of cell sheet constructs: The interplay of human-derived periodontal ligament stem cells, endothelial cells and plasma rich in growth factors.

OBJECTIVE: The aim of this study was to produce and characterize triple-layered cell sheet constructs with varying cell compositions combined or not with the fibrin membrane scaffold obtained by the technology of Plasma Rich in Growth Factors (mPRGF). MATERIALS AND METHODS: Human primary cultures of periodontal ligament stem cells (hPDLSCs) were isolated, and their stemness nature was evaluated. Three types of triple-layered composite constructs were generated, composed solely of hPDLSCs or combined with human umbilical vein endothelial cells (HUVECs), either as a sandwiched endothelial layer or as coculture sheets of both cell phenotypes. These three triple-layered constructs were also manufactured using mPRGF as cell sheets' support. Necrosis, glucose consumption, secretion of extracellular matrix proteins and synthesis of proangiogenic factors were determined. Histological evaluations and proteomic analyses were also performed. RESULTS: The inclusion of HUVECs did not clearly improve the properties of the multilayered constructs and yet hindered their optimal conformation. The presence of mPRGF prevented the shrinkage of cell sheets, stimulated the metabolic activity and increased the matrix synthesis. At the proteome level, mPRGF conferred a dramatic advantage to the hPDLSC constructs in their ability to provide a suitable environment for tissue regeneration by inducing the expression of proteins necessary for bone morphogenesis and cellular proliferation. CONCLUSIONS: hPDLSCs' triple-layer construct onto mPRGF emerges as the optimal structure for its use in regenerative therapeutics. CLINICAL RELEVANCE: These results suggest the suitability of mPRGF as a promising tool to support cell sheet formation by improving their handling and biological functions.