In the field of platelet concentrates for surgical use, most products are termed Platelet-Rich Plasma (PRP). Unfortunately, this term is very general and incomplete, leading to many confusions in the scientific database. In this article, a panel of experts discusses this issue and proposes an accurate and simple terminology system for platelet concentrates for surgical use. Four main categories of products can be easily defined, depending on their leukocyte content and fibrin architecture: Pure Platelet-Rich Plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; Leukocyteand Platelet-Rich Plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan, Angel or GPS PRP; Pure Plaletet-Rich Fibrin (P-PRF), such as Fibrinet; and Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Choukroun's PRF. P-PRP and L-PRP refer to the unactivated liquid form of these products, their activated versions being respectively named P-PRP gels and L-PRP gels. The purpose of this search for a terminology consensus is to plead for a more serious characterization of these products. Researchers have to be aware of the complex nature of these living biomaterials, in order to avoid misunderstandings and erroneous conclusions. Understanding the biomaterials or believing in the magic of growth factors ? From this choice depends the future of the field.

More or less after a decade of experimental and pioneering manual procedures to prepare platelet-rich plasma (PRP) for topical use, several portable and bedside devices were made available to prepare the PRP at the point-of-care. This technical opportunity increased the number of patients who got access to the treatment with autologous PRP and PRP-gel. Since topical treatment of tissue with PRP and PRP-gel was restricted to autologous preparation, blood transfusion centers that professionally prepare donor-derived platelet concentrates were not able to cover the overwhelming request for autologous PRP supply. Principally for logistic and organization reasons blood transfusion centers usually fail the challenge of prompt delivery of PRP to the physician over large territory. Nevertheless the blood bank production of platelet concentrates is associated with high standardization and quality controls not achievable from bedside and portable devices. Furthermore it easy to demonstrate that high-volume blood bank-produced platelet concentrates are less expensive than low-volume PRP produced by portable and bedside devices. Taking also in consideration the ever-increasing safety of the blood components, the relationship between bedside device-produced and blood-bank-produced PRP might be reconsidered. Here we discuss this topic concluding that the variety of sources of PRP production is an opportunity for versatility and that, ultimately, versatility is an opportunity for the patient's care.

Topical treatment with platelet derivatives has increasingly been described as being capable of accelerating wound healing and to aid in tissue repair. In vitro data indicate that platelets and their contents have chemotactic, migration-inducing, and mitogenic activities, and a major role of these factors in tissue repair has thus been advocated. However, how platelet-derived factors orchestrate tissue repair at the cellular level remains quite obscure even to those individuals who prescribe platelet derivatives as topical wound healing therapy. The primary objective of this review was to provide the practitioner, inexpert in biochemistry, an overview about signal transduction within cells in response to platelet-derived factors. Concepts from the literature were selected to illustrate how a relatively few units of information can be put together in specific order to allow for complex biologic functions to be elicited. To illustrate how functional complexity emerges from a narrow set of messengers, an analogy between signal transduction and language, or contrapunctual music, has been drawn.

Background The rationale for using topical platelet gel therapy is to provide the healing tissues with concentrated platelet‐derived factors. Several systems are available to prepare platelet‐rich plasma (PRP) and from these, the platelet gel. These systems produce two‐ to six‐fold platelet and growth factor‐enriched concentrations. The bioavailability of growth factors in tissue healing depends on the amount of growth factors stored in platelets but a portion of these is lost during platelet manipulation. Very few data have been reported on the kinetics of growth factor release from PRP‐gels. The aim of this study is to assess the growth factor recovery and its bioavailability to tissues in four different PRP and PRP‐gel preparation techniques.Materials and methods Three commercially available devices (Fibrinet®, RegenPRP‐Kit®, Plateltex®) and one manual procedure (home made, HM) were evaluated with reference to resulting platelet concentration, growth factor content and the kinetics of growth factor release from gel.Results Platelet concentration increased from 1·65‐ to 4·4‐fold in comparison with whole blood initially used. The final platelet concentration (× 103/µl) was: Fibrinet 1358 ± 419, Regen 430 ± 109, HM 1196 ± 188, and Plateltex 1160 ± 164. A high variation (5‐ to 27‐fold) was found in growth factor concentration in relation to the method used and also a high variation in the kinetics of growth factor release from gels.Conclusions Similar methods for platelet gel preparation revealed different performances concerning growth factor recovery and the kinetics of its release from the gel. It is unclear whether these noticeable differences are important for clinical management.

Background The platelet gel is made by embedding concentrate platelets within a semisolid (gel) network of polymerized fibrin. It is believed that this blood component will be used more and more in the treatment of several clinical conditions and as an adjunctive material in tissue engineering. Several systems are available to produce platelet‐rich plasma (PRP) for topical therapy. Recently, a new system became commercially available, Plateltex®. Here we report the technical performance of this system in comparison with the performance of other commercially available systems: PRGF®, PRP‐Landesber, Curasan®, PCCS®, Harvest®, Vivostat®, Regen® and Fibrinet®.Material and Methods Both the PRP and the gel were prepared according to the manufacturer's directions. The blood samples of 20 donors were used. The yield, the efficiency, and the amount of platelet‐derived growth factor AB (PDGF‐AB), transforming growth factor β, vascular endothelial growth factor and fibroblast growth factor were measured in the resulting PRP. The feature of the batroxobin‐induced gelation was evaluated.Results The yield, the collection efficiency and the growth factor content of Plateltex® were comparable to those of most of the other available systems. The gelation time was not dependent on the fibrinogen concentration; however, it was strongly influenced by the contact surface area of the container where the clotting reaction took place (P < 0·0001).Conclusions Plateltex® provided platelet recovery, collection efficiency and PDGF‐AB availability close to those provided by other systems marketed with the same intended use. Batroxobin, the enzyme provided to induce gelation, acts differently from thrombin, which is used by most other systems. Platelets treated with thrombin become activated; they release their growth factors quickly. Furthermore, thrombin–platelet interaction is a physiological mechanism that hastens the clot‐retraction rate. On the contrary, platelets treated with batroxobin do not become activated; they are passively entrapped within the fibrin network, and their growth factor release occurs slowly. In these conditions, the clot retraction takes longer to occur. According to these differences between thrombin and batroxobin, it is expected that batroxobin‐induced PRP activation will tailor slow release of the platelet content, thus, providing longer in loco availability of trophic factors. In selected clinical conditions, this durable anabolic factor availability might be preferable to quick thrombin‐induced growth factor release.

Background PubMed accessed on January 23 revealed 160 items about ‘platelet gel or releasate’ associated to topical therapy. Yahoo! provided 8580 items; Altavista 8650; Google 25 300. Companies providing blood separators are going to offer devices to prepare platelet‐rich plasma (PRP) for topical therapy. Several devices are filling the marketplace aiming to produce platelet gels for human therapy. Never‐ending lists of clinical conditions supposed to benefit from platelet gel application are published. Clinical benefits include bactericidal activity, pain reduction, tissue repair and regeneration. Are platelet derivatives the magic bullet for topical therapy? Methods Many in vitro studies account for clinical benefit from platelet gel. Several in vivo studies provide clinical evidence about healing of tissue repair induced by platelet derivatives. Nevertheless, systematic reviews reveal inadequate studies providing enough methodological strength to confirm evidence‐based efficacy. At present we must deal the subject with care using mostly inductive criteria. Only reproducible scientific data are to be considered. Every effort should be made for commercial, private and personal popularity‐related scenarios to be rejected from our consideration. Sometimes, this is not so simple to be done. Results There is a list of more than 60 biologically active platelet‐derived factors directly involved in tissue repair mechanisms: chemotaxis, cell proliferation, angiogenesis, extracellular matrix deposition and remodelling. Biological functions are also indirectly mediated by platelet‐derived growth factors; such functions are triggered by chemokines and cytokines produced by bystander cells such as fibroblasts, macrophages, endothelial cells, lymphocytes, under platelet‐derived factor stimulation. All of this is well demonstrated. Clinical studies endorsed with stringent randomized controlled trials are lacking. However, several serious studies have been published reporting clinical efficacy of platelet derivatives in many clinical areas. Considering these papers seriously, we maintain that in most cases, clinical efficacy is by far more than just a suggestion. Discussion Although we consider evidence‐based medicine (EBM) highly meaningful, we emphasize that medicine moved forwards also before EBM was conceived. We do not consider platelet gel and releasate such as a ‘magic bullet’, but we are strongly impressed by the results our group, and other groups have obtained treating a variety of tissue lesions in a variety of clinical conditions. Clinical benefits are a composite result of the lesion state, severity and duration, coexisting pathologies, patient's age and product characteristics. From our point of view, the last is a pivotal variable that has strong influence over the clinical outcome. Platelet‐rich plasma, platelet gel and platelet releasate need stringent definitions. Too many methods are used to prepare these products. Both methods and product need definition, validation, specific quality parameters and clinical indications. Further biologic and biochemical studies are needed as well to understand (if possible to modulate) the inner mechanisms of healing induced by topical treatment with platelet derivatives.

Background: Both recombinant and wild-type platelet-derived growth factors have been demonstrated to enhance soft and bony tissue healing. Experimental animal trials and human experiences have largely demonstrated that platelet-derived factors induce short-time bone-tissue regeneration, while long-term effects including morphogenetics and bone remodelling remain questionable. Frequently, orthopaedic and trauma surgery has to do with bony-tissue defects needing reconstruction. In this case platelet-derived growth factor seems to be recommended to hasten recovery time.

The goal of the study was the evaluation of the effect of modification of titanium implants by acrylic acid surface grafting-collagen I coupling. Tests were performed on titanium samples treated by galvanostatic anodization to create a porous surface topography. Surface characterization by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) confirms the biochemical modification of the surface and shows a surface topography characterized by pores mostly below 1 mum diameter. In vitro evaluation involving human mesenchymal cells shows enhanced cell growth on collagen coated surfaces as compared to titanium ones. Four weeks in vivo evaluation of implants in rabbit femur trabecular bone shows improvements of bone-to-implant contact, while improvement of bone ingrowth is slightly not significant (p = 0.056), when compared to the control. Overall, these data indicate that integration in trabecular, or cancellous, bone can be enhanced by the surface collagen layer, confirming previous findings obtained by modification of machined surfaces by the same approach in cortical bone implants.

Transfusion MedicineVolume 16, Issue 4 p. 303-304 Platelet gel – the Italian way: a call for procedure standardization and quality control P. Borzini, Corresponding Author P. Borzini * Blood Transfusion Centre,Department of Haematology and Transfusion Medicine,Ospedale Santi Antonio e Biagio, Alessandria,I-15100 and † Section of Transfusion Methodologies,Department of Haematology, Oncology andMolecular Medicine,Istituto Superiore di Sanità,Rome, I-00161 Italy.Piero Borzini; e-mail: pborzini@ospedale.al.itSearch for more papers by this authorL. Mazzucco, L. Mazzucco * Blood Transfusion Centre,Department of Haematology and Transfusion Medicine,Ospedale Santi Antonio e Biagio, Alessandria,I-15100 and † Section of Transfusion Methodologies,Department of Haematology, Oncology andMolecular Medicine,Istituto Superiore di Sanità,Rome, I-00161 Italy.Search for more papers by this authorA. Giampaolo, A. Giampaolo * Blood Transfusion Centre,Department of Haematology and Transfusion Medicine,Ospedale Santi Antonio e Biagio, Alessandria,I-15100 and † Section of Transfusion Methodologies,Department of Haematology, Oncology andMolecular Medicine,Istituto Superiore di Sanità,Rome, I-00161 Italy.Search for more papers by this authorH. J. Hassan, H. J. Hassan * Blood Transfusion Centre,Department of Haematology and Transfusion Medicine,Ospedale Santi Antonio e Biagio, Alessandria,I-15100 and † Section of Transfusion Methodologies,Department of Haematology, Oncology andMolecular Medicine,Istituto Superiore di Sanità,Rome, I-00161 Italy.Search for more papers by this author P. Borzini, Corresponding Author P. Borzini * Blood Transfusion Centre,Department of Haematology and Transfusion Medicine,Ospedale Santi Antonio e Biagio, Alessandria,I-15100 and † Section of Transfusion Methodologies,Department of Haematology, Oncology andMolecular Medicine,Istituto Superiore di Sanità,Rome, I-00161 Italy.Piero Borzini; e-mail: pborzini@ospedale.al.itSearch for more papers by this authorL. Mazzucco, L. Mazzucco * Blood Transfusion Centre,Department of Haematology and Transfusion Medicine,Ospedale Santi Antonio e Biagio, Alessandria,I-15100 and † Section of Transfusion Methodologies,Department of Haematology, Oncology andMolecular Medicine,Istituto Superiore di Sanità,Rome, I-00161 Italy.Search for more papers by this authorA. Giampaolo, A. Giampaolo * Blood Transfusion Centre,Department of Haematology and Transfusion Medicine,Ospedale Santi Antonio e Biagio, Alessandria,I-15100 and † Section of Transfusion Methodologies,Department of Haematology, Oncology andMolecular Medicine,Istituto Superiore di Sanità,Rome, I-00161 Italy.Search for more papers by this authorH. J. Hassan, H. J. Hassan * Blood Transfusion Centre,Department of Haematology and Transfusion Medicine,Ospedale Santi Antonio e Biagio, Alessandria,I-15100 and † Section of Transfusion Methodologies,Department of Haematology, Oncology andMolecular Medicine,Istituto Superiore di Sanità,Rome, I-00161 Italy.Search for more papers by this author First published: 25 July 2006 https://doi.org/10.1111/j.1365-3148.2006.00680.xCitations: 12Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume16, Issue4August 2006Pages 303-304 RelatedInformation

PURPOSE OF REVIEW:This review addresses potential roles for platelets and their derivatives (gels, releasates, and lysates) as therapeutic agents for regenerative medicine. Recognizing that activated platelets release chemotactic and growth factors, investigators have attempted to enhance tissue regeneration by applying platelets and various derivatives directly into sites of surgical interventions or injuries. This review analyzes the physiologic basis for this approach to tissue healing and examines the knowledge that has been derived from recent and relevant reports of in-vitro and in-vivo studies. RECENT FINDINGS:In-vitro studies have established that platelets and their derivatives accelerate proliferation of an array of cells involved in soft and bony tissue regeneration. These effects have been evaluated, also, in vivo in humans and in animals. The outcomes of in-vivo studies are considerable less homogeneous than the outcomes of in-vitro investigations. The resultant discrepancies reflect not only differences of technical protocols, but also the greater complexity of healing vital tissues compared with circumscribed in-vitro studies. SUMMARY:The preponderance of evidence indicates that platelets and their derivatives have the potential for a substantial therapeutic role in tissue regeneration. The results of recent research indicate that platelet-derived growth factors act in synergy with plasma-derived factors to activate a complex network of autocrine functions that modulate healing. Platelet-derivative products are promising therapeutics that offer new opportunities for research and applications of tissue engineering.

Background and objectives Recipients of peripheral blood progenitor cells (PBPC) are prone to opportunistic infections and their lives depend upon the availability of PBPC. Centres responsible for PBPC processing are committed to provide patients with products which are as safe as possible. These must be processed under quality assurance requirements. Materials and methods A retrospective analysis of PBPC processed in a single centre according to quality assurance premises was carried out to define the rate and the cause of microbiologic contamination and bag ruptures. Results 940 microbiologic cultures were run on 725 cryopreserved bags. Five bacterial strains were identified in the positive cultures. The rate of bacterial contamination was 1.85% of the patients, 0.34% of the collected bags, and 0.79% of the reinfused bags. Bag ruptures occurred in 1.06% of the thawed bags. Conclusions Permanent quality control of peripheral progenitor cell processing is mandatory. Preventive measures such as ex vivo cell manipulation in a clean room facility and the use of a double-bagged technique are highly recommended to prevent bacterial contamination and to rescue progenitor cells in the case of a bag rupture if those cells are necessary for the haematopoietic reconstitution of a patient.

Vox SanguinisVolume 88, Issue 1 p. 61-61 The ability of HPA-5b typing to predict vascular occlusion events P. Borzini, Corresponding Author P. Borzini Transfusion Medicine, ‘Ospedale SS Antonio e Biagio’, Alessandria, ItalyPiero Borzini MD, DirectorServizio di Medicina TrasfusionaleAzienda Ospedaliera ‘SS Antonio e Biagio e C. Arrigo’Via Venezia 1615100 Alessandria ALItalyE-mail: pborzini@ospedale.al.itSearch for more papers by this authorL. Mazzucco, L. Mazzucco Transfusion Medicine, ‘Ospedale SS Antonio e Biagio’, Alessandria, ItalySearch for more papers by this author P. Borzini, Corresponding Author P. Borzini Transfusion Medicine, ‘Ospedale SS Antonio e Biagio’, Alessandria, ItalyPiero Borzini MD, DirectorServizio di Medicina TrasfusionaleAzienda Ospedaliera ‘SS Antonio e Biagio e C. Arrigo’Via Venezia 1615100 Alessandria ALItalyE-mail: pborzini@ospedale.al.itSearch for more papers by this authorL. Mazzucco, L. Mazzucco Transfusion Medicine, ‘Ospedale SS Antonio e Biagio’, Alessandria, ItalySearch for more papers by this author First published: 21 January 2005 https://doi.org/10.1111/j.1423-0410.2005.00598.xCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume88, Issue1January 2005Pages 61-61 RelatedInformation

BACKGROUND: In loco administration of platelet (PLT) derivatives is a relatively new auxiliary treatment for tissue regeneration to be hastened. Enthusiastic reports are faced by more critical ones. The more obvious rationale for the in vivo administration of PLT derivatives resides in their growth factor content.STUDY DESIGN AND METHODS: The relevant literature was systematically reviewed. Close scrutiny of the technical details was carried out to find out the procedural differences accounting for conflicting results.RESULTS: An impressively vast heterogeneity of conduct was found in both in vitro and in vivo studies. Major outcome-affecting variables were recognized such as those associated with PLT preparation; growth factor measurement; proliferation test; dose, timing, and administration of the PLT derivatives; study design; and primary endpoints.CONCLUSIONS: So many variables were found making standardization or confrontation of the in vitro and the in vivo studies barely conceivable or manageable. The mechanisms of action are very complex. The attribution of tissue regeneration capacity of PLT derivatives solely to the PLT-derived growth factors is simplistic. The results obtained through in vitro experiments are indicative for general mechanisms. Their simplistic hold to the complex in vivo environment may be misleading.

s of the 8th European Symposium on Platelet and Granulocyte Immunobiology, Seehotel Rust, Rust, Austria, May 13–16, 2004

BACKGROUND: Chronic ulcers can benefit from topical treatment with growth factors (GFs). PLT gel provides tissue regeneration-inducing GFs. The aim of this study was to verify the effectiveness of autologous PLT gel in the treatment of nonhealing skin lesions.STUDY DESIGN AND METHODS: PLT gel was produced by treating PLTs with autologous thrombin. Two groups of patients were investigated: patients with dehiscent sternal wounds and patients with necrotic skin ulcers. Patients treated with PLT gel were retrospectively compared with patients having similar lesions but undergoing conventional treatment. The clinical endpoints of the study were the healing rate, the length of hospital stay, and/or the time required to bring about adequate tissue regeneration in order to undergo reconstructive plastic surgery.RESULTS: In patients with treated dehiscent sternal wounds the healing rate (3.5 vs. 6.0 wks, p = 0.0002) and hospital stay (31.5 vs. 52.5 days, p < 0.0001) were significantly reduced. Patients with treated necrotic skin ulcers required a notably shorter time to have surgery (median 15.0 vs. 35.5 wks, p < 0.0001). Neither adverse reactions nor in-situ recurrences were observed.CONCLUSIONS: Patients with chronic unhealing wounds showed substantial improvement when treated with PLT gel lesion dressings.

We evaluated the recovery of platelet count after 348 platelet transfusions administered to 98 patients with hematologic diseases. The aim of the study was to evaluate the effects of detrimental factors impairing a good recovery of the platelet count. We found that: (1) despite the rates of patients with immune or clinical detrimental factors being similar (7.1% vs 9.1%), alloimmunized patients received up to 40.5% of all platelet concentrates; (2) autoantibody-like antibodies do not cause refractoriness; (3) apheresis- and buffy coat-derived platelet concentrates have quite similar clinical effects.

TransfusionVolume 41, Issue 11 p. 1456-1456 Universal WBC reduction Piero Borzini MD, Piero Borzini MD Servizio Immunotrasfusionale Ospedale S.S. Antonio e Biagio 15100 Alessandria, Italy e-mail: [email protected]Search for more papers by this author Piero Borzini MD, Piero Borzini MD Servizio Immunotrasfusionale Ospedale S.S. Antonio e Biagio 15100 Alessandria, Italy e-mail: [email protected]Search for more papers by this author First published: 24 November 2002 https://doi.org/10.1046/j.1537-2995.2001.41111456.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume41, Issue11November 2001Pages 1456-1456 RelatedInformation