Chronic ulcers or non-healing ulcers are defined as spontaneous or traumatic lesions, typically in lower extremities that are unresponsive to initial therapy or that persist despite appropriate care and do not proceed towards healing in a defined time period with an underlying etiology that may be related to systemic disease or local disorders [1, 2]. There are many types of non-healing ulcers that may include venous, arterial, diabetic, pressure and traumatic ulcers. The normal wound healing process is dynamic and complex having three phases: inflammation, tissue formation and tissue remodeling. However, if the normal healing process is interrupted, an ulcer can become chronic in nature due to lack of growth factors and cytokines which delay the healing process . Lower extremity ulcers comprise a substantial proportion of chronic ulcers, especially those attributed to venous disease, diabetes, or arterial disease . Chronic non-healing ulcer is a major health problem and is estimated to affect approximately 2–6 million people in the United States alone [2, 4], while its prevalence in the world ranges from 1.9 to 13.1% [5, 6]. The incidence of chronic ulcers is expected to increase as the population ages and due to increased risk factors for atherosclerotic occlusion such as smoking, obesity and diabetes. It is estimated that almost 10% of the population would develop a chronic wound in the course of a lifetime, with wound related mortality rate of 2.5% . These types of ulcers not only affect the quality of life and productivity of the patient but also become a substantial financial burden for the patient and the healthcare system .
“More than 85% of lower limb amputations are preceded by foot or ankle ulcers and diabetes is one of the major causes of non-traumatic amputations across the world” . Approximately 15–25% of individuals with diabetes develop a foot ulcer, of which an estimated 12% require lower extremity amputation . Individuals with diabetic foot ulcers are susceptible to infection and the healing process is complicated by diabetic neuropathy leading to chronic non-healing ulcers. Majority of the chronic lower extremity ulcers are accounted by venous disease as venous hypertension results in damage to vessel walls and ultimately lead to skin breakdown . The prevalence of venous non-healing ulcers varies between 1 and 2% in the general population that accounts for almost 75–80% of all vascular ulcers [1, 9, 10].
The goal of ulcer treatment is to obtain wound closure as expeditiously as possible. Conventional treatment for non-healing ulcers includes wound cleansing, necrotic tissue debridement, prevention, diagnosis, and, if necessary, treatment of infection, mechanical off-loading, management of blood glucose levels and local ulcer care with dressing application [2, 11, 12]. However, there are certain risk factors that commonly affect and contribute to poor wound healing, these include: 1) Local causes, such as presence of debris or necrotic tissue, infection in the ulcer, tissue hypoxia, and repeated trauma; 2) Systemic diseases, such as diabetes mellitus, immunodeficiency, or malnutrition; and 3) Medications, such as corticosteroids .
The standard available treatment modalities for non-healing ulcers address these issues and provide optimal local ulcer therapy with debridement of necrotic tissue and provision of a moist wound healing environment, pressure relief in the wound area, infection management using antibiotics, antiseptics and topical antibacterial agents, ischemia management, and medical management of comorbidities. A wide variety of advanced treatment for non-healing ulcer include hyperbaric oxygen therapy, skin grafting, VAC (vacuum assisted closure) and surgical management like angioplasty and reconstructive surgery as needed [3, 13, 14].
Despite treatment, many chronic ulcers fail to heal or persist for months/years and/or recur after healing, requiring additional advanced wound care therapies for adequate healing . Cellular therapy for the treatment of non-healing ulcer has been a major breakthrough in the arena of vascular therapies. The use of patient’s own body cells for wound/ulcer treatment relies upon the components present in the blood and platelet concentrate, which contains various cytokines and growth factors. These modular treatment options are safe and effective and have no side effects. Over the last two decades, emerging cellular therapies such as platelet-rich plasma (PRP) therapy has gathered considerable attention for its potential use in the field of regenerative medicine as a therapeutic agent in a range of chronic conditions and can have an adjunctive role in a standardized, quality treatment plan [13, 15]. Autologous PRP is a platelet suspension in plasma derived from whole blood that is increasingly being used in clinical practice for the treatment of chronic ulcers. The concentration of platelets in PRP is 2–6 folds higher than that of whole blood [1, 16]. The curative properties of PRP rely on the fact that platelets are a physiological reservoir of a variety of growth factors, with healing function which have an active role in tissue regeneration .
PRP is increasingly being used as a new alternative approach in various fields of medicine (i.e. dentistry, traumatology, cosmetic surgery, ophthalmology, and dermatology). Platelets contain proteins, known as growth factors that trigger biological effects including directed cell migration (i.e. chemotaxis), angiogenesis, cell proliferation and differentiation, which are key elements in the process of tissue repair and regeneration. Several studies have also been published on the role of platelet rich plasma for the treatment of non-healing ulcers with positive response .
PRP is most often mixed with thrombin before application in order to generate a fibrin gel, and a platelet-growth-factors-rich exudate . Thrombin activated platelets release numerous growth factors from their \( \alpha \)-granules  that can modulate cell proliferation and differentiation and accelerate soft tissue repair in vivo .
A recent meta-analysis of the use of PRP therapy in cutaneous wounds showed that compared to control wound care, PRP facilitated wound healing and the ulcers improved significantly in small hard-to-heal acute and chronic wounds [21, 22]. In addition, platelets exert antimicrobial activity against some bacteria of the skin, and clinical data shows that the presence of infection is reduced in PRP-treated wounds . Therefore, PRP therapy has several advantages that can provide a practical and effective treatment approach for small hard-to-heal ulcers .
Autologous Platelet Rich Plasma treatment for Non-healing ulcers has been a breakthrough in the stimulation and acceleration of soft-tissue healing. PRP therapy helps create a biological environment internally that is most conducive for restoration of tissue homeostasis by providing numerous signalling cytokines and growth factors that are important in tissue repair by diverse mechanisms including the regulation of inflammation, angiogenesis, and synthesis and remodelling of new tissue . The advantages and merits of PRP are apparent since it is easy, cost-effective and much more lasting compared to other standard treatments and being autologous in nature, it is free from communicable pathogens, making it a safe treatment modality with good clinical results [10, 21].
The purpose of the present case series was to evaluate the safety and efficacy of autologous PRP in treating non-healing ulcer on lower extremity using a rapid, intra-operative point-of-care technology at the patients’ bed side.