INTRODUCTION

Platelet-rich plasma (PRP) is an autologous blood product with a high concentration of platelets and growth factors. Because PRP is an autologous preparation, the risk of allergic reaction is generally considered low; however, adverse effects, including infections, may occur [1]. It is obtained from blood collected from the patient, by centrifugation, which leads to the separation of the individual blood components. As a result, a preparation with a very high content of compounds synthesized and released by activated platelets is obtained. These include numerous platelet chemotactic factors, such as fibrinogen, thrombospondin, von Willebrand factors, adenosine diphosphate (ADP), adenosine triphosphate (ATP), serotonin, Ca²⁺, platelet-activating factor (PAF), platelet-derived growth factor (PDGF), platelet factor 4 (PF4), β-thromboglobulin (btg), interleukins (IL-1β and IL-8), CD40 ligand, P-selectin, transforming growth factor (TGF), epidermal growth factor (EGF), insulin-like growth factor (IGF) and vascular endothelial growth factor (VEGF) [2]. These substances are signaling molecules that promote tissue repair and wound healing [3]. Chronic wounds and ulcers are skin defects of mixed etiology requiring a long healing and treatment process and tend to recur periodically [4].

PRP is a biological product containing three to seven times more platelets than baseline blood levels, as well as various growth and bioactive factors that promote angiogenesis and cell proliferation and modulate inflammation [5]. This supraphysiological platelet concentration enables increased cell proliferation, regeneration, differentiation, and collagen production, which may accelerate skin regeneration, healing, and repair. Injection of concentrated platelets into the wound site initiates the hemostatic cascade, synthesis of new connective tissue, and revascularization. PRP concentrates can stimulate an above-average release of growth factors, thereby rapidly initiating healing in both chronic and acute wounds [6].

Wound healing is a complex process involving many biological mechanisms, the course of which largely depends on environmental factors and factors directly related to the regenerative capacity of the host. Importantly, some wounds heal spontaneously and require no special treatment, whereas others will not heal without appropriate medical intervention [7].

Chronic, difficult-to-heal wounds, such as diabetic ulcers, burns or pressure ulcers, represent a significant financial burden for patients and healthcare systems. Their treatment involves substantial costs related to additional visits to healthcare facilities, frequent dressing changes, nursing care, and hospital stays [8]. Therefore, it is important to seek methods that are effective in treating wounds that are not responsive to traditional treatment and that reduce healing time as much as possible.

Because of the aging global population and the high prevalence of chronic diseases among elderly individuals, the number of patients with chronic wounds is expected to continue to increase [8]. The treatment of chronic wounds, such as diabetic foot ulcers and pressure ulcers, remains a global challenge, and PRP therapy is a promising method for treating these conditions.

The aim of this study is to summarize the literature on the treatment of chronic wounds using PRP.

PLASMA COMPOSITION

Plasma composition and functions of individual factors are presented in table 1 [9, 10].

PLASMA COLLECTION TECHNIQUE

The plasma collection technique involves drawing 10 to 60 ml of venous blood into a test tube containing sodium citrate as an anticoagulant, which prevents platelet activation, degranulation, and premature release of effector molecules.

Initial centrifugation of whole blood separates red blood cells (RBCs) from plasma, and subsequent centrifugation separates PRP, which contains a large number of platelets and leukocytes, from the cell-free platelet-poor plasma.

The PRP precipitate is then treated with calcium chloride or thrombin to activate platelets and polymerize fibrin. The final preparation is platelet-rich, usually reaching a concentration of approximately 1 million platelets/ml, which is 2 to 8 times higher than that of whole blood [9–11].

Approximately 90% of the growth factors contained within the platelets are released within the first 10 minutes after activation. Many growth factors have very short half-lives, suggesting that platelet activation should be performed at the time of injection or shortly before injection to achieve the greatest efficacy [12].

Like any medical procedure, platelet-rich plasma has both advantages and disadvantages, the most important of which are presented in table 2.

PRESSURE ULCERS

A pressure ulcer (PU) is caused by prolonged pressure on the skin, which impairs blood circulation and may result in tissue injury, disruption of skin integrity, ulceration, and even necrosis due to insufficient nutrition of the skin and subcutaneous tissue [13]. The most common sites of PU occurrence are the sacrum, buttocks, and heels, and treatment depends on ulcer severity. PRP, due to its regenerative properties, has been used in the treatment of difficult-to-heal ulcers [14].

Wound care includes debridement and cleansing, treatment of infection if present, and the use of dressings. Various dressing materials have been used, including hydrocolloid, hydrogel, and alginate dressings. Other wound care methods, such as negative pressure wound therapy, surgical management, autologous PDGF, and adjunctive therapies like electrical stimulation, hydrotherapy, hyperbaric oxygen therapy, and autologous PRP, are also used in clinical practice [15]. Due to the impaired wound healing process and prolonged inflammatory phase, PRP is increasingly used for therapeutic purposes. Autologous agents that promote wound healing by supporting granulation tissue formation in the early stages of healing are useful in the treatment of chronic ulcers, including pus.

In the group of patients in whom the treatment of pus with hydrogel and PRP was compared, clinical improvement was observed. However, healing with granulation tissue formation was faster in patients treated with PRP, suggesting a potential advantage of this treatment method [15, 16].

Moreover, epithelial tissue regeneration appears to be enhanced by PRP. Similar effects have been observed for angiogenesis [17].

In the treatment of difficult-to-heal pus, PRP may accelerate wound healing, reduce pain, shorten the healing period, regulate the expression of specific proteins in granulation tissue, reduce levels of inflammatory factors such as IL-1β, IL-8, and TNF-α and improve patients’ quality of life without increasing complications.

Patients may function better from psychological, physiological, social, and daily activity domains, as assessed using the World Health Organization Quality of Life Scale (WHOQOL-BREF) [18].

Studies have shown that injection of autologous PRP at the site of injury is effective in clinical practice; however, PRP administered as a spray has also been found to be an effective form of application [18].

PRP may effectively reduce inflammation in patients with pus, promote wound repair and scar remodeling, and significantly improve clinical efficacy [13].

BURN WOUNDS

Burn wounds are traumatic injuries that are underestimated by physicians. This type of wound may occur as a result of exposure to various factors, including heat, radiation, chemicals, cold, or electricity, although most burns are caused by heat. All burn injuries involve tissue destruction [19].

Burn wounds are classified according to the depth of tissue injury. Previously, the classification was based on degrees 1–4; however, this has now largely been replaced by terminology describing superficial, partial-thickness, and full-thickness tissue injury.

First-degree burns are superficial wounds affecting only the epidermis. The epidermis is red, swollen, and painful.

Second-degree burns are partial-thickness injuries. This type of burn penetrates into the dermis, but only into its superficial layer. Characteristic features of this degree include blisters presence.

Third-degree burns are full-thickness injuries that destroy both the epidermis and dermis. Third-degree burns may also involve subcutaneous tissue.

Fourth-degree burns are full-thickness injuries extending beyond the epidermis and dermis into underlying tissues, such as fascia, muscles, or bones [20].

A study conducted between 2010 and 2014 at the Dutch Burn Center of the Red Cross Hospital in Beverwijk, the Netherlands, focused on the use of PRP in burn wound treatment. In this study, autologous buffy-coat PRP was used. This type of PRP contains both platelets and leukocytes. During the procedures, burn wounds were cleaned by surgeons, who then selected two comparable wound areas of similar depth and size. PRP was applied using a dual-syringe system. After plasma application, the wounds were covered with a non-adhesive dressing and left for 5–7 days [21].

After this period, the dressing was removed. Primary early outcomes showed no statistically significant difference between PRP-treated and non-PRP-treated areas. Pain and itch also did not differ between PRP-treated and non-PRP-treated wounds. No difference in scar quality was observed between PRP and non-PRP wounds [21].

This study suggests that PRP does not appear to improve wound healing or scar formation in acute burns [21].

THE USE OF PLATELET-RICH PLASMA IN DIABETIC FOOT WOUND HEALING

According to the World Health Organization (WHO), diabetic foot syndrome is characterized by the presence of infection, ulceration, deep tissue destruction, and features of neuropathy and ischemia of varying severity. The main factors contributing to foot ulcers in patients with diabetes are diabetic neuropathy and lower limb ischemia [22]. Diabetic foot syndrome not only negatively affects the patients’ health but also represents a significant economic burden due to the cost of proper ulcer care, increased frequency of medical interventions, and possible hospitalizations [23].

Hyperglycemia is one of the factors that lead to an impaired inflammatory response, inadequate proliferation, migration, and differentiation of skin fibroblasts and keratinocytes, and impaired release of growth factors by these cells [24–26]. In patients with diabetes, an impaired inflammatory response and reduced tissue perfusion lead to an increased risk of wound colonization by pathogens, further impeding the healing process. Consequently, ulcers occurring in diabetic foot syndrome are refractory wounds that increase the risk of limb amputation and disability [22]. Studies indicate that up to 88% of lower limb amputations are associated with diabetic ulcers [27]. Adequate wound care is therefore an important factor in preventing infection and possible limb loss. Standard wound care methods, however, may not be sufficient. Therefore, it seems important to search for adjunctive ulcer care methods that are effective and widely available from an economic point of view. One such adjunctive method may be the use of PRP.

Due to its high platelet concentration, PRP acts by releasing various cytokines and growth factors. These compounds promote cellular processes necessary for tissue repair, thereby supporting wound healing and accelerating the body’s natural repair mechanisms [28]. These properties may therefore be used to reduce the healing time of diabetic ulcers. Studies have confirmed the effectiveness of PRP in the treatment of ulcers in patients with diabetes.

A study conducted by Malekpour Alamdari et al. confirmed the clinical effectiveness of PRP in the healing of foot ulcers in patients with diabetes. The study included patients with diabetic foot syndrome who were randomly assigned to two groups. The study group was treated with PRP gel, whereas the control group received a conventional dressing. The study showed that ulcer healing time was significantly shorter in the study group, with an average of 55 days, compared with 80 days in the control group [29].

Li et al. retrospectively examined the efficacy and safety of autologous platelet-rich gel (APG) in the treatment of diabetic foot ulcers. Patients were divided into a study group and a control group. Patients in both groups received standard ulcer care, while those in the study group additionally received APG. Diabetic foot ulcer healing time, length of hospitalization, cure rate, and overall efficacy rate differed significantly between the groups, as shown in table 3 [30].

Ahmed et al. conducted a study at Suez Canal University Hospital in Egypt between 2012 and 2014 to compare the outcomes of treating diabetic foot ulcers using PRP versus standard methods. At the end of week 12, ulcers had healed in 68% of patients in the control group compared with 86% of patients in the study group [31].

The International Diabetes Federation (IDF) projects a rapid increase in the prevalence of diabetes from 10.5% (536.6 million people aged 20–79) in 2021 to 12.2% (783.2 million people aged 20–79) by 2045 [23]. In view of the above, the development of effective treatments for diabetes complications, including ulcers caused by diabetic foot syndrome, should be an important area of research. The cited studies indicate that PRP may be a promising option in the treatment of refractory chronic ulcers in diabetic foot syndrome. The possibility of shortening the healing process may also be significant from a public healthcare perspective. An additional advantage of this treatment is the low risk of debilitating local and systemic adverse effects, as well as the low risk of immune reactions.

CHRONIC VENOUS LEG ULCERS

Venous leg ulcers (VLUs) are open skin lesions that occur in areas affected by venous hypertension. VLUs are the most common cause of lower limb ulcers in developed countries, and their incidence increases with age. In Australia, VLUs are the most common chronic wounds in the community [32]. Patients with VLUs experience a significant reduction in quality of life. VLUs may also cause severe complications, including infections and malignant transformation. Current treatment methods include compression therapy, exercise, bandages, pentoxifylline, and tissue products. Compression bandaging of the lower leg is the most commonly used treatment method to reduce hydrostatic pressure in the limb [33]. However, even with optimal compression therapy, healing time is often prolonged and outcomes may be insufficient to achieve complete and sustained healing.

Therefore, there is a strong need for new treatment options for VLUs to accelerate and improve wound healing. Scientific reports have described the use of autologous APG as an adjunct to compression therapy in VLU healing.

APG is mainly produced by adding thrombin and divalent calcium ions to PRP, which results in platelet and clotting factor activation, growth factor release, and the formation of a viscous fibrin-containing gel [34]. APG has been used for more than 20 years to reduce blood loss during surgery and is increasingly being used in wound and bone healing [35, 36]. The main mechanism of action of APG is the release of growth factors that trigger tissue regeneration [37].

However, the combination of APG and biodegradable gelatin hydrogel as a wound dressing is still being investigated to ensure sustained release and improve the biological half-life of growth factors derived from PRP.

A prospective observational study was conducted to investigate whether the use of PRP dressings would reduce healing time in patients with chronic venous leg ulcers. It included 100 patients with diagnosed venous insufficiency of the lower extremities complicated by leg or foot ulceration, following angioplasty of a narrowed artery. Patients were divided into two groups of 50 each: those treated with PRP dressings (study group) and those treated with conventional hydrocolloid dressings (control group). At regular intervals, treatment effects were monitored, and the appearance, area, and depth of wounds were compared and assessed using ultrasound. The granulation process was examined histologically to document skin formation and neovascularization of the wound tissue. Treatment with PRP dressings resulted in a significant gradual reduction in ulcer size, regardless of the initial ulcer size, compared with conventional dressings. Moreover, the greatest effect of PRP was observed in the category of the largest wounds. After 1 month of treatment with PRP dressings, more than 50% of all ulcers were completely healed. New epidermis appeared together with granulation tissue, and dermis formation was observed after 20 days of treatment [34].

CONCLUSIONS

PRP therapy, derived from the patient’s own blood, represents a safe and well-tolerated treatment option for non-healing wounds. Its autologous nature reduces the risk of allergic reactions, and adverse effects are rare. Clinical evidence indicates that PRP may accelerate tissue regeneration by modulating inflammatory responses and stimulating the proliferation of fibroblasts and keratinocytes, resulting in faster epithelialization, granulation tissue formation, and neovascularization.

Studies have shown that PRP, especially in combination with compression therapy, may reduce the size of venous leg ulcers and accelerate healing. Similarly, in chronic ulcers associated with diabetic foot syndrome, incorporating PRP into standard care may improve treatment outcomes and reduce the risk of complications, including limb amputation. Furthermore, PRP appears to be a valuable adjunctive option in pressure ulcer therapy by promoting tissue regeneration and reducing inflammation, which may improve patients’ quality of life.

However, PRP therapy has limitations. Although its efficacy in various chronic wound treatments has been reported, studies evaluating its use in burn treatment have not shown significant benefits compared with standard care. This underscores the need for further research to refine PRP application protocols, including plasma preparation, activation methods, and delivery techniques.

As the population ages and chronic diseases become increasingly prevalent, PRP therapy offers a promising approach to reduce healthcare costs by shortening treatment duration and hospital stays while improving outcomes in patients with chronic wounds. Continued efforts to optimize and standardize PRP protocols are essential to fully determine its therapeutic potential and ensure consistent benefits across different patient populations.

Overall, PRP may provide greater benefits when used as an adjunct to standard wound care rather than as a stand-alone therapy, particularly in chronic, difficult-to-heal wounds.