Biological Treatments with Plasma Rich Platelet (PRP) Without Side Effects for Total Decrease of Chronic Pain and Inflammation

Dr. Stergios Oikonomidis, MD, PhD. Orthopaedic surgeon, physiologist, ozon therapist
Dr. Ioannis Toliopoulos, PhD. Physiology, post doct in immunology of reproductive medicine

Konstantinion Research Center uses PRP in all its possible applications in order to improve or treat any chronic inflammatory diseases and chronic musculoskeletal problems with no side effects.

The center uses two methodologies of PRP depending on its application after the blood draw from the patient. The application of PRP is performed with thin needles in the trigger point of the damage by expert doctors and no side effects.
It has to be noted that before, during and after the applicaton of PRP, the research center will perform immunological testing for the progress of inflammation by measuring specific cytokines which play major role in the chronic pain or inflammation after taking blood or other biological fluid. By this way PRP will be evaluated with clinic laboratorial tests for the quality evidence based medicine.

What is PRP and what are its Applications?

Platelet-rich plasma (PRP), platelet-rich concentrate, autologous platelet gel or platelet releasate, all refer to one concept, which is an autologous concentration of human platelets contained in a small volume of plasma. It is known for a long time that fibrin clot and platelets have haemostatic and tissue repairing effect. In 1975, an article was published with the concept of platelet gel under the title of: ‘use of platelet-fibrinogen-thrombin mixture as a corneal adhesive. An exciting report was published in 1979 about the usage of gel foam in sutureless nerve anastomosis. After a few years an animal model showed that platelets and fibrin initiate a process consist of cell migration, collagen synthesis, fibroplasia and angiogensis which helps the lesion healing. The real application of platelet releasate in treating wounds, has begun in the mid-1980s after publication of Kingthon et al. in 1986.
In 1997 another important report was published about the maxillofacial surgery and platelet gels. The usages of platelet gel became more popular in late 1990s, after the publication (1998) of a paper about the effectiveness of the platelet-rich plasma (PRP) in bone regeneration in the field of dental care.

There are several growth factors in α-granules of platelets, secreted after the activation of platelets by aggregation initiators. These factors including platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF) regulate cell migration and attachment. Some studies indicate that platelets have anti-inflammatory and analgesic effects and secrete antimicrobial peptides, thus have antibiotic effects. More than 800 proteins are secreted in this matrix affect on various cell types: osteoblasts, chondrocytes, fibroblasts, endothelial cells, mesenchymal stem cells from different origins, myocytes and tendon cells which lead to a wide range of surgical and clinical procedures and treatments which help the platelet concentrated products.
Nowadays, there are publications about the use of PRP in chronic wound treatment, soft tissue injuries, periodontal and oral surgery, maxillofacial surgery, orthopedic and trauma surgery, spinal surgery, heart bypass surgery, burns, cosmetic and plastic surgery, gastrointestinal surgeries. We want to summarize the use of PRP in dermatology especially in skin rejuvenization.
Skin rejuvenation

In the past decade, PRP has attracted the attention of dermatologists specifically in the aesthetic field for skin rejuvenation.
Skin aging

Aging skins has obvious characteristics such as red-brown-mottled dyschromia, dryness and fine wrinkles. Moreover, cell replacement and wound healing decrease with age and some changes take place in skin texture such as sagging and wrinkling. Aged skin is known histologicaly, by a flattened dermo–epidermal junction, dermal atrophy and fewer fibroblasts. Among different degenerative processes cause skin aging, decreasing in fibroblasts collagen production the most important one. Interaction of fibroblasts with keratinocytes, adipocytes and mast cells is important in skin aging processes. In addition, they are loaded with several kinds of ECM (extra cellular matrix) proteins, glycoproteins, adhesive molecules and cytokines. They produce these molecules, strengthen the skin cell interactions and participate in fibroblast-keratinocyte-endothelium axis that preserves skin integrity and youth. Several cytokines and growth factors work in the stimulation process of fibroblasts for collagen synthesis.

Nowadays, there is an increasing amount of harmful effects on the skin such as malignancies, immuno-suppression, hyper pigmentation, wrinkles, aging and etc., due to the increasing rate of UV radiation.

The prolonged human skin exposure to sun or UV irradiation lowers the resilient properties of the skin and so degenerates the three-dimensional structure of resilient fibers (elastotic degeneration), disorganizes collagen fibrils which lead to decreasing the skin flexibility. The UV radiation incorporates by special chromophore in the skin, such as melanin, deoxyribonucleic acid (DNA), ribonucleic acid, proteins, lipids, water, aromatic amino acids, trans-urocanic acid and etc. Which consequently create reactive oxygen species (ROS) (34). ROS makes histochemical changes: the stratum spinosum thickening and dermoepidermal junction flattening.

On the other hand, the studies have shown the effect of growth factors and cytokines in preserving the skin texture such as fibroblast growth factor (FGF1) which is important in the regeneration and proliferation process of skin cells, accumulation of collagen type 1 alpha 1 protein in skin and inhibition of UV-induced skin damages.
Conventional anti-aging strategies, such as those involving lasers and topical treatments, typically aim to increase ECM synthesis through the activation of fibroblasts.

Anti aging mechanisms of PRP

Platelet concentration is a rich source of various cytokines and growth factors, which are activated after its injection into the target tissue. Platelets are activated endogenously by coagulation factors (in some methods of preparing PRP, the activated PRP is injected to the tissue). Following their attachment to special receptors on the cell surfaces, some intracellular processes are activated, that facilitate extracellular matrix (ECM) accumulation and improve cell proliferation and differentiation. Tissue regeneration is resulted from cell proliferation, angiogenesis and cell migration.

Matrix metaloproteinas proteins (MMP) are involved in aging process by degradation of collagen and other extracellular matrix (ECM) proteins (38), this characteristic can be used to benefit rejuvenation. They can help regeneration of dermis through omission of collagen fragments that are harmful to the dermal connective tissue, and so, provide an appropriate foundation for new collagen deposition (38). In some studies aPRP (activated PRP) increases the expression of MMP-1 and MMP-3 protein. Thus, aPRP may cause ECM remodeling through stimulating the removal of photo-damaged ECM components and inducing the synthesis of new collagen by fibroblasts, which are in turn proliferated by their stimulation.
Another study showed that high concentration of PRP increased type I collagen, MMP-1 and MMP-2 expression in human skin fibroblasts.

In addition to above mechanisms, improving aging skin through PRP which is a dose-response relationship has been recognized between concentrated platelet and mesenchymal stem cell proliferation.

Another mechanism of PRP for skin rejuvenization, is through acceleration of hyaluronic acid production. Hyaluronic acid absorbs water and makes hyaluronic acid matrix swelled which increases skin volume and turgor. It also promotes cell proliferation, extracellular matrix synthesis and helps to the adjustment of the collagen fibers diameter. Overall, it could enhance skin elasticity. All these processes and some other unknown ones contribute to tissue rejuvenation through PRP.

Recent studies demonstrated that injection of PRP in the face and neck for the purpose of revitalization would lead to promising outcomes. Some studies suggest that PRP may have value in rejuvenation of wrinkled and sagging skin. Although, methods of PRP application such as topical application or direct injection are being investigated, there is yet no definite method for clinical use of PRP.

Platelet Rich Plasma (PRP) is used for stimulation of both superficial and deep dermis layers. For superficial stimulation, the injection must be done in the superficial dermis. The PRP must be injected into the deep dermis or subdermal tissues when using as filler. The superficial injection might be done just like mesotherapy technique in order to improve the skin texture, volume and hydration. The technique is easy to be performed and has no important side-effects. Side-effects might appear from mild bruising and occasional swelling to rarely infections.

Some other study has demonstrated PRP as a beneficial primary or adjunctive treatment (adjuvant treatment to lasers) for the tissue rejuvenation . Another study has assigned contraindications for PRP application which consists of pregnancy, breastfeeding, malignancy, autoimmune or blood diseases.

NOTE: For successful application of PRP, important factors are the experience, specialty, and the high morale and deontology of the doctors.

For info email:

• Mehta S, Watson JT. Platelet rich concentrate: basic science and current clinical applications. J Orthop Trauma. 2008;22:432-438.
• Redaelli A, Romano D, Marciano A. Face and neck revitalization with platelet-rich plasma (PRP): clinical outcome in a series of 23 consecutively treated patients. J Drugs Dermatol. 2010;9:466-472.
• Shin MK, Lee JH, Lee SJ, et al. Platelet-rich plasma combined with fractional laser therapy for skin rejuvenation. Dermatol Surg. 2012; 38: 623-630.
• Borzini P, Mazzucco I, Blackwell P. Platelet-rich plasma (PRP) and platelet derivatives for topical therapy. What is true from the biologic view point? ISBT Science Series. 2007; 2: 272 -281.
• Marx RE, Carlson ER, Eichstaedt RM, et al. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998; 85: 638-646.
• Fischer H. A method of suture-free anastomosis of nerve transplantation is being reported, using facial nerve as the example. Laryngol Rhinol Otol. 1979;58:154–156.
• Knighton DR, Hunt TK, Thakral KK, et al. Role of platelets and fibrin in the healing sequence: an in vivo study of angiogenesis and collagen synthesis. Ann Surg. 1982;196:379–388.
• Knighton DR, Ciresi KF, Fiegel VD, et al. Classification and treatment of chronic nonhealing wounds. Successful treatment with autologous platelet-derived wound healing factors (PDWHF). Ann Surg. 1986;204:322–330.
• Marx RE, Carlson ER, Eichstaedt RM, et al. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85:638–646.

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