Platelet-Rich Plasma in Dermatology: New Insights on the Cellular Mechanism of Skin Repair and Regeneration

Abstract

The skin's recognised functions may undergo physiological alterations due to ageing, manifesting as varying degrees of facial wrinkles, diminished tautness, density, and volume. Additionally, these functions can be disrupted (patho)physiologically through various physical and chemical injuries, including surgical trauma, accidents, or chronic conditions like ulcers associated with diabetes mellitus, venous insufficiency, or obesity. Advancements in therapeutic interventions that boost the skin's innate regenerative abilities could significantly enhance patient care protocols. The application of Platelet-Rich Plasma (PRP) is widely recognized for its aesthetic and functional benefits to the skin. Yet, the endorsement of PRP's advantages often borders on the dogmatic, with its efficacy commonly ascribed solely to the activation of fibroblasts by the factors contained within platelet granules. PRP therapy is a cornerstone of regenerative medicine which involves the autologous delivery of conditioned plasma enriched by platelets. This is achieved by centrifugation, removing erythrocytes while retaining platelets and their granules. Despite its widespread use, the precise sequences of cellular activation, the specific cellular players, and the molecular machinery that drive PRP-facilitated healing are still enigmatic. There is still a paucity of definitive and robust studies elucidating these mechanisms. In recent years, telocytes (TCs)-a unique dermal cell population-have shown promising potential for tissue regeneration in various organs, including the dermis. TCs' participation in neo-angiogenesis, akin to that attributed to PRP, and their role in tissue remodelling and repair processes within the interstitia of several organs (including the dermis), offer intriguing insights. Their potential to contribute to, or possibly orchestrate, the skin regeneration process following PRP treatment has elicited considerable interest. Therefore, pursuing a comprehensive understanding of the cellular and molecular mechanisms at work, particularly those involving TCs, their temporal involvement in structural recovery following injury, and the interconnected biological events in skin wound healing and regeneration represents a compelling field of study.

Keywords: aesthetic dermatology; autologous transplant; platelet-rich plasma; skin regeneration; skin repairing; telocytes.

Figure 1

The injury of the skin triggers a series of physiologic and morphological events for repairing the injured structures. This cascade of healing falls into four overlapping phases. The hemostasis phase (primarily about coagulation) is acute and begins with injury, followed by the formation of the blood clot that dams the bloodshed; the platelets become activated by their contact with basement membranes and collagen fibres and begin aggreging. Thrombin initiates the formation of the fibrin mesh. The inflammatory phase (which is mainly about removing the cellular debris) is orchestrated by neutrophils and macrophages and their variegated secretory panel. Clinically, it lasts about 6 days and the Celsus cardinal signs feature this phase. The proliferative phase (which is about filling and covering the skin defect) structurally features the formation of the granular tissue and neoangiogenesis and wound covering by the neighbouring epithelial cells. All these intricate processes can last about 3 weeks. In both the inflammatory and proliferative phases, the formerly destroyed network of interstitial cells (including telocytes, TCs) is restored to its initial parameters. The maturation phase (dominated by structural remodelling and reorganization processes) is the longest-lasting and is dominated by the rearrangement and maturation of the collagens, increasing the tensile strength. Thus, the cellular architects of the phase are the fibroblasts (Fbs) and fibrocytes. RBC—red blood cell; Plt—platelets; L—leukocytes; myFb—myofibroblast; ly—lymphocytes. The image was created with BioRender.com.

Figure 2

Transmission electron microscopy image of a platelet. Under the plasma membrane normal platelet specific organelles are present. The entire volume presents scarce α–granules (αg) and δ-granules (δg) among several mitochondria (m) and multiple granules of glycogen (gly). The elements of the open canalicular system (OCS) indicate its three-dimensional distribution within the entire platelet volume. A scant distribution of Golgi apparatus (GA) elements is also visible. (Courtesy of Dr. E.T. Fertig, “Victor Babeş” National Institute of Pathology, Bucharest, Romania).

Figure 3

Transmission electron microscopy image of a platelet. The peripheral distribution of the microtubular (mt) loop is obvious and demonstrates its implication in platelet morphology and shape maintenance. Three-dimensionally open canalicular system (OCS) elements are present, along with glycogen granules (gly), mitochondria (m), α–granules (αg), and δ-granules (δg). (Courtesy of Dr. E.T. Fertig, “Victor Babeş” National Institute of Pathology, Bucharest, Romania).

Figure 4

Transmission electron microscopy image of two neighbouring platelets (Plt₁ and Plt₂). Plt₁ is in close proximity to a just-shedded multivesicular cargo (MVC)—a complex group of platelet-derived membrane-bound structures that activate and regulate intercellular pathways. MVC are vectors of transport for nucleic acids, proteins, and lipids, regulating the local microenvironment (but also remotely) with implications in cellular functions’ modulation or tissue regeneration/repair. gly—glycogen; m—mitochondria; OCS—open canalicular system. (Courtesy of Dr. E.T. Fertig, “Victor Babeş” National Institute of Pathology, Bucharest, Romania).

Figure 5

Providing a platelet-rich plasma (PRP) treatment to the site of the skin injury helps the structural recovery in terms of speediness and the performant regeneration of affected cutaneous components. Considering the myriad of growth factors and cytokines, it is attractive to presume that PRP is eliciting the vascular recovery of telocytes (TCs), cells with a documented angiogenic potential within the interstitia of other organs. Inset: platelets could stimulate the involvement of TCs (by their cellular prolongations—telopodes) as nursing cells for the new-formed blood vessels. Plt—platelets; RBC—red blood cells; End—endothelial cell; Ma—macrophage; Fb—fibroblast; Ly—lymphocyte; Eo—eosinophil; PMN—neutrophil. The image was created with BioRender.com.