How does it work?
It is well known that the wound healing process is complex and typically divided into three phases; inflammatory, regeneration, and remodelling. A number of proteins are contained within the platelet’s alpha-granules. Collectively, these proteins are members of the families of growth factors, cytokines and chemokines, which are broadly referred to as secretory proteins. They are of prime importance in the realisation of this entire process as each step of the healing cascade is under the influence of specific growth factors/cytokines14. Some investigators have suggested that PRP should achieve a 3- to 5-fold increase in platelet concentration over baseline5,10,15.
Owing to the presence of high concentrations of growth factors, apart from the wide use to accelerate wound healing, PRP has been used in a wide variety of surgical procedures and clinical treatments. Indeed, there is substantial clinical evidence regarding its use in other medical fields14, 16. The substantial concentration of platelets, compared with normal blood, certainly represents a unique source of growth factors. Following subcutaneous injection, these proteins and growth factors interact with the basal cells in the subcutaneous tissue, including fibroblasts, endothelial cells, and subcutaneous stem cells. PRP is also used in the aesthetic field for the stimulation of the superficial dermis, as well as the deep layers of the dermis. It has been proven that PRP application both augments the skin and increases its volume17, 18.
Fitzpatrick published a study proving that topical application of growth factors stimulate the rejuvenation of photoaged facial skin, improving its clinical appearance and inducing new collagen synthesis19, 20, and another research study showed that PRP actually induces increased expression of G1 cell cycle regulators, type I collagen, and matrix metalloproteinase (MMP)-1 in human dermal fibroblasts21.
[pull_quote align=”right” ]PRP must be developed in an anti-coagulated state and should be used on the graft, flap, wound, or skin within 10 minutes of clot initiation. [/pull_quote]
Cells, osteoblasts, fibroblasts, endothelial cells, and epidermal cells express the cell membrane receptors to growth factors in PRP. These transmembrane receptors in turn induce an activation of an endogenous internal signal protein, which causes the expression of (unlocks) a normal gene sequence of the cell such as cellular proliferation, matrix formation, osteoid production, and collagen synthesis. The significance of this is that the PRP growth factors never enter the cell or its nucleus, are not mutagenic, and act through the stimulation of normal healing, but much faster. Therefore, PRP has no ability to induce tumour formation and has never been found to do so22, 23.
PRP must be developed in an anti-coagulated state and should be used on the graft, flap, wound, or skin within 10 minutes of clot initiation. There is a doseÐresponse relationship between platelet concentration and the proliferation of human adult mesenchymal stem cells, the proliferation of fibroblasts, and the production of type I collagen24, 25. This suggests that the application of autologous PRP can enhance wound healing, as has been demonstrated in controlled animal studies for both soft and hard tissues26, 27.
The next question, therefore, concerns how many platelets are enough. A sufficient cellular response to platelet concentrations first began when a 4- to 5-fold increase over baseline platelet numbers was achieved24. A similar study by Lui and al25 showed that fibroblast proliferation and type I collagen production were also enhanced by increasing platelet concentrations and that much of the response was pH-dependent, with the best responses occurring at more acidic pH levels.
PRP is rapidly gaining a lot of interest worldwide, but health regulations differ from country to country, making the generalisation of the process more complicated and often more expensive. For example, in Korea it is possible to carry out a half-face study, which is not possible in the UK, and in Italy, the process can be performed only in a clinic/hospital with a haematologist on site.
When using PRP, the different methods used during preparation are important as they influence the quality of the product. Activation of the platelets is required for the release and enmeshment of growth factors, but the method of activation may influence the resulting matrix, growth factor availability, and healing28. Furthermore, some methods enrich leukocytes as well as platelets, but others are designed to be leukocyte-poor. Leukocytes have many important roles in healing and their inclusion in PRP results in increased platelet concentrations. Generally, TGF- 1 and PDGF levels are higher in preparations that contain leukocytes compared with leukocyte-poor PRP28.
The literature published between March 2001 and March 2011 was reviewed by Davis et al29, and the meta-analysis of chronic wound studies revealed that PRP therapy is favoured for complete healing. This systematic review in cutaneous wounds showed complete and partial wound healing was improved compared with control wound care.
Within the eligible studies, three main types of wounds were identified and treated with PRP: open and chronic wounds, acute surgical wounds with primary closure, and acute surgical wounds with secondary closure30, 31. The primary outcome assessed in this systematic review was complete healing32. In both chronic and acute wound studies, complete wound closure was more likely in wounds treated with PRP therapy. Another review concluded that the percentage of total healing in PRP-treated skin ulcers consistently increased compared with controls18. Other reviews on PRP therapy have reached the same conclusions.
One systematic review went so far as to conclude that, based on the meta-analysis and scientific evidence regarding consistent favourable outcomes, PRP is a treatment of choice for the topical care of wounds33. A total of 15 randomised controlled trials and 25 case-control studies were found. Thirty-six publications demonstrated favourable outcomes with the use of PRP. The included articles were divided into three topics related to cosmetic surgery: wound healing, fat grafting and bone grafting. Carter et al33 described a substantially beneficial effect of PRP for a number of indications, including a better wound healing rate, an increased survival rate of fat grafts, and an enhancement of bone graft regeneration.