20 June 2012, Volume 26 Issue 2(S1)

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  • Editorial
    Journal of Biological Regulators and Homeostatic Agents. 2012, 26(2(S1)): 1-1.
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  • A Lubkowska, B Dolegowska, G Banfi
    Journal of Biological Regulators and Homeostatic Agents. 2012, 26(2(S1)): 3-22.
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    This paper reviews available reports on the advantages and possibilities of clinical use of platelet-rich plasma preparations, with particular emphasis on platelet growth factors. Platelets, an important reservoir of growth factors in the body, play an important role in many processes such as coagulation, immune response, angiogenesis and the healing of damaged tissues. Numerous proteins are contained in the alpha-granules of platelets: platelet-derived growth factor (PDGF), transforming growth factor (TGF), platelet factor interleukin (IL), platelet-derived angiogenesis factor (PDAF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor IGF and fibronectin. The development of methods and systems for blood and cell sorting (e.g. CAPSS - compact advanced platelet sequestration system Elektromedics 500, PCCS - platelet concentrate collection system Curasan) have made it possible to obtain significant concentrations of platelets (even by 338 percent) and high concentrations of growth factors, in a form of sterile mass that can be used immediately for clinical purposes. Platelet-rich plasma (PRP; autologous platelet-rich plasma - APRP) are platelet concentrates made of autogenous blood with a high number of platelets in a small volume of plasma. The clinical efficacy of platelet concentrates depends mainly on the number of platelets and the concentration of their growth factors, which act as transmitters in most processes in tissues, particularly in healing where they are responsible for proliferation, differentiation, chemotaxis and tissue morphogenesis. They operate as part of autocrine, paracrine and endocrine mechanisms. Growth factors derived from centrifuged blood were first used in patients with chronic skin ulcers. The clinical use of PRP for a wide variety of applications has been reported mostly in oral and maxillo-facial surgery, orthopedic surgery, treatment of soft tissue diseases and injuries, treatment of burns, hard-to-heal wounds, tissue engineering and implantology.

  • B Dolegowska, A Lubkowska, L De Girolamo
    Journal of Biological Regulators and Homeostatic Agents. 2012, 26(2(S1)): 23-33.
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    Lipids account for 16-19 percent dry platelet matter and includes 65 percent phospholipids, 25 percent neutral lipids and about 8 percent glycosphingolipids. The cell membrane that surrounds platelets is a bilayer that contains different types phospholipids symmetrically distributed in resting platelets, such as phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine, and sphingomyelin. The collapse of lipid asymmetry is exposure of phosphatidylserine in the external leaflet of the plasma bilayer, where it is known to serve at least two major functions: providing a platform for development of the blood coagulation cascade and presenting the signal that induces phagocytosis of apoptotic cells. During activation, this asymmetrical distribution becomes disrupted, and PS and PE become exposed on the cell surface. The transbilayer movement of phosphatidylserine is responsible for the platelet procoagulant activity. Exposure of phosphatidylserine is a flag for macrophage recognition and clearance from the circulation. Platelets, stored at room temperature for transfusion for more than 5 days, undergo changes collectively known as platelet storage lesions. Thus, the platelet lipid composition and its possible modifications over time are crucial for efficacy of platelet rich plasma therapy. Moreover, a number of substances derived from lipids are contained into platelets. Eicosanoids are lipid signaling mediators generated by the action of lipoxygenase and include prostaglandins, thromboxane A2, 12-hydroxyeicosatetraenoic acid. Isoprostanes have a chemical structure similar to this of prostanoids, but are differently produced into the particle, and are ligands for prostaglandins receptors, exhibiting biological activity like thromboxane A2. Endocannabinoids are derivatives from arachidonic acid which could reduce local pain. Phospholipids growth factors (sphingolipids, lysophosphatidic acid, platelet-activating factor) are involved in tissue regenerating process. Finally, a warning concerning the atherogenic role of platelets, although it should not be exerted in a local therapy, is mentioned. The lipid content of plaletets must be taken into account when these particles are concentrated and used for a local therapy, while the different categories of lipid derivatives could improve or affect the quality of the product.

  • E Galliera, M M Corsi, G Banfi
    Journal of Biological Regulators and Homeostatic Agents. 2012, 26(2(S1)): 35-42.
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    Inflammation represents a fundamental aspect of the healing process. Besides their primary role in hemostasis, platelets play an active role in the immunological and inflammatory aspect of tissue healing. Indeed , they can be directly involved in the inflammatory response by the production and release of several inflammatory mediators, including a variety of cytokines, such as TGF-beta, IL-1 beta, CD40L, and chemokines, such as CXCL7, CXCL4, CXCL4L1, CCl5, CXCL1, CXCL8, CXCL5, CXCL12, CCL2, CCL3. Platelet are not only a source of several chemokine involved in the inflammatory response and tissue healing, but they also express chemokine receptors, in particular CCR1 CCR3 CCR4 and CXCR4, thus being able to being able to regulate the inflammatory response associated to the healing process. However, this local inflammation must be taken under control, and platelets can prevent the excess of leukocytes recruitment by anti-inflammatory cytokines, such as TGF-beta. For this biological properties of platelets, platelet rich plasma therapy (PRP) is considered an innovative and promising approach that has been extended to many field of medicine, ranging from non-union defects, bone fractures, spinal fusion, bone implant and osteointegration, joint arthroplasty, to the treatment of several traumatic or degenerative pathologies of tendons, cartilage and ligaments.

  • A Cieslik-Bielecka, D M Dohan Ehrenfest, A Lubkowska, T Bielecki
    Journal of Biological Regulators and Homeostatic Agents. 2012, 26(2(S1)): 43-52.
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    Platelets, as main actors of the first stage of the healing process, play an important role in tissue repair. Their granules contain many active substances, particularly over 30 growth factors with significant effects on the resident cells at the site of injury, such as mesenchymal stem cells, chondrocytes, fibroblasts, osteoblasts. This potential may be increased by the concentration of the platelets, using platelet-rich plasma/fibrin products. In the four families of platelet concentrates, 2 families contain also significant concentrations of leukocytes: L-PRP (Leukocyte- and Platelet-Rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). Inductive properties of platelet concentrates were widely described. However, they present also antimicrobial effects. The antibacterial effects of L-PRP were highlighted in only a few in vitro studies. Strong activity comparable to gentamicin and oxacillin for L-PRP against methicillin susceptible Staphylococcus aureus (MSSA) was already demonstrated. L-PRP also inhibited the growth of methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli. Some authors also reported clinical observations about the reduction of infections and the induction of healing processes after the use of platelet concentrates in cardiac, orthopaedic, oral and maxillofacial surgery. However, very little is yet known about the antibacterial effects of these concentrates. In this manuscript, the current data about the antimicrobial agents and cells present in the platelet-rich plasma/fibrin are highlighted and discussed, in order to introduce this new key chapter of the platelet concentrate technology history.

  • D Stanco, M Vigano', S J Croiset, L De Girolamo
    Journal of Biological Regulators and Homeostatic Agents. 2012, 26(2(S1)): 53-61.
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    Platelet-rich plasma (PRP) is a promising alternative approach based on the efficacy of autologous growth factors to accelerate tissue healing, allowing a fast recovery after muscles, ligaments, tendon or cartilage lesions. This literature review begin focusing on the role of platelets growth factors in these tissue healing and on the available preparation methods for PRP. Moreover we consider the in vitro and in vivo study on PRP, some of the most important therapeutic applications and limitations. Although several preclinical studies show promising results, clinical studies still show controversial results. Further studies are required to define the efficacy and to specify the way of using PRP in the orthopaedic practice.

  • J Yoo, S Chandarana, K Fung, J H Franklin, A C Nichols, P C Doyle
    Journal of Biological Regulators and Homeostatic Agents. 2012, 26(2(S1)): 63-69.
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    Objectives: To evaluate the effect of autologous platelet and plasma adhesives (APA) on postoperative drainage and soft-tissue fibrosis following neck dissections.Design: This was a blinded comparative prospective cohort study done as two parts: part one evaluated early post-surgical outcomes and part two evaluated late tissue fibrosis.Method: Salvage neck dissections were stratified into two groups based on severity of prior treatment. High risk patients were defined as those who had previously undergone chemoradiation therapy and autologous platelet adhesives were administered to the surgical wound intraoperatively. The low risk group consisted of patients undergoing salvage neck dissections following radiation only and acted as controls. Part one evaluated postsurgical wound drainage as the primary outcome as well as length of hospital stay and complications. Part two evaluated late postoperative tissue fibrosis by comparing neck skin using the Cutometer. R2 and F0 were the specific Cutometer parameters for quantifying the viscoelastic properties of the skin.Results: Postoperative wound drainage was significantly less (253.7 vs. 345.8) in the autologous platelet adhesive group as compared to the control group (p less than 0.03). Length of stay in the APA group versus the control group was 3.13 and 3.86 days respectively (p less than 0.004). Both R2 and F0 measurements showed improved viscoelastic properties of the skin in the APA group (R2 p less than 0.05, F0 p less than 0.05).Conclusions: APA application following salvage neck dissections may reduce early postperative wound drainage and improve long-term skin quality.

  • J I Torrero, F Aroles, D Ferrer
    Journal of Biological Regulators and Homeostatic Agents. 2012, 26(2(S1)): 71-78.
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    Application of new biological treatments in orthopaedics is controversial nowadays. Surgeons and practitioners know how difficult can be to choose a solution for chondral injuries. Joint damages are from little contusions, osteochondral fractures, avascular necrosis, osteochondritis and degenerative processes like osteoarthritis and rheumatisms. All mentioned have a common problem: the lack of regenerating hyaline cartilage by themselves. Recently, PRP have been used to treat early moderate chondropathies. Here we show the preliminary results of 30 patients affected by chondropathy of the knee after 6 months treated with a single intrarticular injection of PRP. Thirty patients, 18-65 years old, with a diagnosis of I to III Outerbridge chondropathy in the knee, pain for more than 3 months following conservative treatment and no bone axial defect, were treated with one intraarticular injection of PRP (GPS mini set, BIOMET), after written consent and Ethic and Legal Committee approval. VAS and KOOS scores were evaluated before PRP injection and at 1, 3 and 6 months after the treatment. ANOVA with repeated measures using the SPSS showed significantly better results in term of KOOS and VAS scores at 1, 3 and 6 months respect to the pre-injection value (p less than 0,05) We think that PRP treatment is a promising alternative for the treatment of knee chondropathy; however its efficacy has to be demonstrated with more clinical works, with longer follow up and with greater number of patients, even with controlled and randomized trials. In our study only one injection of PRP has been able to allow a clinical improvement, suggesting the possibility to avoid multiple injections protocols, and consequently reducing the health expenses. Until the efficacy of PRP will not be definitely demonstrated, surgeon should be very prudent in indications.