PLATELET-RICH PLASMA 2009 

PLATELET-RICH PLASMA (PRP): EVIDENCE FOR CLINICAL AND THERAPEUTIC USE

The leading definitive published work covering important fields in surgery, regarding the application of autologous PRP-gel (A-PRP) in aesthetics, plastic surgery and therapeutics, arguably, has been recorded by Professor Robert Marx, an oral and maxillofacial surgeon of repute, and high academic standing, from the University of Miami in the United States(1). Marx et al from the United States and his academic platform has provided evidence, proof-of-concept, regarding the following clinically and relevant scientific aspects of PRP (1):

The application of PRP-gel is well known to surgeons and has a role to play in wound healing (1). It has proven safe, because it is autologous in nature and thereby precludes the danger of infection transmission, provided the plasma-gel is not contaminated during the processing (1). Comparative studies have demonstrated that platelet-yields and growth-factor release/concentration vary somewhat, depending on which device is used to prepare the PRP and how the platelets are activated. REGENLAB-PRP™ blood collection tubes (CE marked), and distributed by Omnimed (Pty.,Ltd) in South Africa, render good results compared to others (2). As of 2008, a new commercial system for the preparation of PRP was launched in Europe, and is marketed as Plateltex®. The technical performance, regarding FDA approved and non-approved devices for clinical generation from human whole venous-blood, has been reported (2). Plateltex® produces rapid batroxibin-induced enzymatic gelation and is suitable for topical application. The Italian group have indicated that Plateltex® is comparable to those of most of the other available systems (2). However, Plateltex® that relies on batroxibin enzyme to induce gelation, acts differently from thrombin (2), which is used by most other systems ( including bovine thrombin[1]).Platelets treated with batroxibin do not become activated, these are apparently entrapped within the fibrin network and offer special advantages at the point of treatment (2).One of the advantages of batroxibin-induced platelet gel is that PRP activation by this enzyme may tailor slow release of the platelet content, possibly providing a more predictable availability of trophic factors (2). The manufacturer of Plateltex®, have indicated that this durable “anabolic factor” availability might be preferable to quick thrombin-induced growth factor release (2). In South Africa , the market leader is REGENLAB™, from Switzerland. The REGENKIT™ and blood collection tubes are used both in the clinic for wound healing and aesthetics (for PRP-mesotherapy, plasma resurfacing and facial rejuvenation) and distributed in South Africa by OMNIMED (Pty),(Ltd) in Randburg. More details on batroxibin-induced PRP activation can be perused at www.plateltex.com. For activation of the platelets, the following are clinical choices available: calcium chloride, calcium gluconate, human and bovine thrombin and ADP( recent Italian studies): Du Toit and co-workers, working independently  in Cape Town, have reported on the biological activity of batroxibin-induced gel (PLATELTEX®) and thrombin-induced gel ( REGENLAB® and REGENKIT®) in biological tissue culture ( see Plateltex® within www.bolandcell.co.za) .Du Toit ( from Cape Town) and Borzini ( from Italy) et al, have reviewed in publication format the application of Regenlab™ and Plateltex® generated autologous PRP in wound care and aesthetic medicine (3).Du Toit and co-workers have further reviewed the clinical application of A-PRP for top journals and added new innovative cell biology , local African experience and tissue culture aspects (4,5). In South Africa, there are 4 systems and devices available commercially to generate PRP. And it seems that there are more on the way. Very favourable healing results have been reported in diabetics with foot ulceration treated with platelet-rich plasma and platelet-gels and confirmed in Cape Town(6).PRP and the role in wound healing is important and reflected in the number of ongoing FDA-approved clinical trials ( Cytomedix® Autologel®, patellar retinacular injuries, Biomet®[ Achilles tendinopathy, tennis elbow],cardiac surgery at The Royal Brompton Hospital, NHS, lower extremity bypass surgery, diabetic foot ulceration and plantar fasciitis)(7).

PRP AND COSMETIC CLINICAL TRIALS: PLATELET-GEL AND PLASMA RESURFACING

There are no registered FDA protocols regarding PRP ( activated platelets with growth factor release) and wrinkle amelioration or rejuvenation of the facial skin, at the time of posting, which attests to the controversial ethical and scientific problems regarding this niche market. Open-ended, uncontrolled studies conducted in non-academic private clinics in England, France, Ireland, Japan and China using the REGENLAB® System has suggested possibility of benefit. For the moment there is no robust science or proof-of-science that PRP plays a major role in facial rejuvenation. Skin analysis have been too crude to detect subtle dermal histological changes. Open-ended studies suggest improvement in skin texture, no effect is visible to underlying age-related pigmentation. Major issues that have marred research in this area has been problems with inconsistent generation of PRP in commercial laboratories by inexperienced workers, complex wrinkle classification, photoaging versus chronological aging and inaccurate skin measurement instruments that are variable in results(even on the same spot). Major obstacles that have precluded FDA trials with PRP and aesthetic medicine include:

However in academic medicine, Marx and co-workers, from Miami, USA, have shown advanced healing of diabetic foot ulceration, rapid healing of skin flaps after face-lifts resulting in reduced inflammation, erythema, swelling and rapid epitheliazation in recipients of PRP(1). This is facilitated by application of the activated PRP to the under surface of the skin-SMAS flap and along the skin incision(1).Marx and workers (2005) have shown that PRP can improve haemostasis, improve flap adherence and accelerate the return of skin sensation via its growth factor stimulation (1). The plasma factors in autologous PRP is a potent stimulus for cells in tissue culture, including fibroblasts, but not more than bovine or foetal calf serum. This has been the experience in Cape Town. See Tissue Culture menu on www.bolandcell.co.za for more information and cell morphology. Du Toit and co-workers, of Cape Town have the most experience regarding PRP generation and application in the clinic and aesthetics with various products in South Africa and have extensive unsurpassed back-up publications in the medical literature, supported by oral presentations at academic and aesthetic congresses ( during 2007, 2008).

CELL THERAPY, FIBROBLASTS AND CLINICAL TRIALS IN COSMETIC AND THE  BEAUTY INDUSTRY

Currently the only approved fibroblast cell therapy FDA protocol, at the time of posting, is of ISOLAGEN INC, that is active but not recruiting. Various factors have contributed to this situation. William Boss, of the United States, is accredited as the doyen of fibroblast auto-transplantation for human living fibroblasts for the amelioration of rhytids; the “ISOLAGEN PROCESS” being patented. Some units have attempted to co-culture human fibroblasts with the donor platelet-rich plasma (PRP).The results have been equivocal with the use of autologous human serum, autologous PRP or bovine/foetal calf serum. In Europe, the biotechnological process of platelet-rich plasma and fibroblast ex vivo cell proliferation has been patented by REGENLAB™, a biotechnology laboratory in Mollen, Switzerland (PTC patent issued during 2007, protecting cell processing in PRP based-mediums). Du Toit and co-workers, from Cape Town, have the largest laboratory and clinical experience of the “ Isolagen Process and manufacture” in South Africa and are active in the field(8). See www.regenlab.com for more information on REGENLAB™, REGENKIT™ and availability of collection tubes in South Africa. Major obstacles that have hampered skin rejuvenation efforts with the clinical application of the patients own living cells (fibroblasts) in commercial laboratories include:

MORE INFORMATION ON APPLICATION OF PRP IN SOUTH AFRICA ( Aesthetics and therapeutics: demonstrations, equipment and training)
Contact: Omnimed (Pty) (Ltd), Randburg, South Africa. Sammi van Rooyen, National Sales Manager at (011) 792-7120

REFERENCES

POSTED 15/10/2008