Leukocyte- And Platelet-rich Plasma Research Articles

The Influence of Leukocyte and Platelet Concentrate Enrich in Stem Cells on Bone Regeneration Processes: A Clinical and Flow Cytometry Study

This article reports the efficacy of percutaneous autologous leukocyte- and platelet-rich plasma (L-PRP) injection into delayed union site as a minimally invasive method alternative to bone marrow aspirate and open grafting techniques. Each of 15 participants was followed on a regular basis with clinical examinations, roentgenograms. The average time to union was 8.4 weeks after L-PRP injection and the union was achieved in all cases. CD34+/45+ cells counts were increased by 410% and CD34+/45- cells counts were increased by 488% on average in L-PRP. Our investigation showed that L-PRP enrich in stem cells can produce the desired stimulatory response despite a substantial amount of vital bone cells from mesenchymal line. We believe that the using of L-PRP enriched in stem cells, growth factors and antimicrobial proteins might be a promising treatment method in regenerative medicine.

Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives

Platelet concentrates for topical and infiltrative use - commonly termed Platetet-Rich Plasma (PRP) or Platelet-Rich Fibrin (PRF) - are used or tested as surgical adjuvants or regenerative medicine preparations in most medical fields, particularly in sports medicine and orthopaedic surgery. Even if these products offer interesting therapeutic perspectives, their clinical relevance is largely debated, as the literature on the topic is often confused and contradictory. The long history of these products was always associated with confusions, mostly related to the lack of consensual terminology, characterization and classification of the many products that were tested in the last 40 years. The current consensus is based on a simple classification system dividing the many products in 4 main families, based on their fibrin architecture and cell content: Pure Platelet-Rich Plasma (P-PRP), such as the PRGF-Endoret technique; Leukocyte- and Platelet-Rich Plasma (LPRP), such as Biomet GPS system; Pure Platelet-Rich Fibrin (P-PRF), such as Fibrinet; Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Intra-Spin L-PRF. The 4 main families of products present different biological signatures and mechanisms, and obvious differences for clinical applications. This classification serves as a basis for further investigations of the effects of these products. Perspectives of evolutions of this classification and terminology are also discussed, particularly concerning the impact of the cell content, preservation and activation on these products in sports medicine and orthopaedics.

A side-effect induced by the combination of a demineralized freeze-dried bone allograft and leucocyte and platelet-rich plasma during treatment for large bone cysts: A 4-year follow-up clinical study

During platelet activation over 30 growth factors are released from their alpha granules. By concentrating platelets, higher levels of growth factors are obtained and can be used to stimulate the healing processes. Moreover, during blood centrifugation, huge numbers of leukocytes and thrombocytes can be obtained to form leukocyte and platelet-rich plasma (L-PRP). After platelet degranulation the active gelatinous matrix called leukocyte and platelet-rich gel (L-PRG) is formed.In the present clinical study, we report the influence of PLRG and freeze-dried allografts on healing of large femoral bone cysts. Each of 6 participants was followed on a regular basis with clinical examinations, roentgenograms and dual-energy X-ray absorptiometry (DXA) examinations.Our four-year follow up clinical study using allografts and PLRG in the treatment of large cystic lesions of the proximal femur showed that mixing these substances is not efficient and it might induce unknown local reactions between them causing complete bone graft destruction. Further studies are necessary to fully understand the mechanisms of the local activity of L-PRP gel.

Applications of Leukocyte- and Platelet-Rich Plasma (L-PRP) in Trauma Surgery

Leukocyte- and platelet-rich plasma (L-PRP) contains high concentrations of platelet, leukocytes and other bioactivities, which play an prominent role in both bone and soft tissue healing processes. Large numbers of studies provide evidence for application of L-PRP in experiments and clinical practice. It has been identified to improve cellular chemotaxis, proliferation and differentiation, angiogenesis, and production of extracellular matrix, but also responsible for stimulating defense mechanisms against infections. L-PRP is now playing an increasing role in the management of patients with traumatic injuries. However, most studies are only anecdotal or case reports, and then larger controlled studies are needed. This article introduces the reader to L-PRP properties and L-PRP applications in trauma surgery, including applications of L-PRP in bone healing, acute soft tissue wound healing, and repairing of acute muscle, tendon, ligament, nerve and cartilage injury caused by trauma.

In Search of a Consensus Terminology in the Field of Platelet Concentrates for Surgical Use: Platelet-Rich Plasma (PRP), Platelet-Rich Fibrin (PRF), Fibrin Gel Polymerization and Leukocytes

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.

Current Knowledge and Perspectives for the Use of Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF) in Oral and Maxillofacial Surgery Part 1: Periodontal and Dentoalveolar Surgery

Platelet concentrates for surgical use are innovative tools of regenerative medicine, and were widely tested in oral and maxillofacial surgery. Unfortunately, the literature on the topic is contradictory and the published data are difficult to sort and interpret. In periodontology and dentoalveolar surgery, the literature is particularly dense about the use of the various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte- and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In this first article, we describe and discuss the current published knowledge about the use of PRP and PRF during tooth avulsion or extraction, mucogingival surgery, Guided Tissue Regeneration (GTR) or bone filling of periodontal intrabony defects, and regeneration of alveolar ridges using Guided Bone Regeneration (GBR), in a comprehensive way and in order to avoid the traps of a confusing literature and to highlight the underlying universal mechanisms of these products. Finally, we particularly insist on the perspectives in this field, through the description and illustration of the systematic use of L-PRF (Leukocyte- and Platelet- Rich Fibrin) clots and membranes during tooth avulsion, cyst exeresis or the treatment of gingival recessions by root coverage. The use of L-PRF also allowed to define new therapeutic principles: NTR (Natural Tissue Regeneration) for the treatment of periodontal intrabony lesions and Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges. In periodontology, this field of research will soon find his golden age by the development of user-friendly platelet concentrate procedures, and the definition of new efficient concepts and clinical protocols.

The Role of Leukocytes from L-PRP/L-PRF in Wound Healing and Immune Defense: New Perspectives

Platelet concentrates for topical use are innovative tools of regenerative medicine and their effects in various therapeutical situations are hotly debated. Unfortunately, this field of research mainly focused on the platelet growth factors, and the fibrin architecture and the leukocyte content of these products are too often neglected. In the four families of platelet concentrates, 2 families contain significant concentrations of leukocytes: L-PRP (Leukocyte- and Platelet-Rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). The presence of leukocytes has a great impact on the biology of these products, not only because of their immune and antibacterial properties, but also because they are turntables of the wound healing process and the local factor regulation. In this article, the various kinds of leukocytes present in a platelet concentrate are described (particularly the various populations of granulocytes and lymphocytes), and we insist on the large diversity of factors and pathways that these cells can use to defend the wound site against infections and to regulate the healing process. Finally, the impact of these cells in the healing properties of the L-PRP and L-PRF is also discussed: if antimicrobial properties were already pointed out, effects in the regulation of cell proliferation and differentiation were also hypothesized. Leukocytes are key actors of many platelet concentrates, and a better understanding of their effects is an important issue for the development of these technologies.

L-PRP/L-PRF in Esthetic Plastic Surgery, Regenerative Medicine of the Skin and Chronic Wounds

The use of platelet concentrates for topical use is of particular interest for the promotion of skin wound healing. Fibrin-based surgical adjuvants are indeed widely used in plastic surgery since many years in order to improve scar healing and wound closure. However, the addition of platelets and their associated growth factors opened a new range of possibilities, particularly for the treatment of chronic skin ulcers and other applications of regenerative medicine on the covering tissues. In the 4 families of platelet concentrates available, 2 families were particularly used and tested in this clinical field: L-PRP (Leukocyte- and Platelet-rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). These 2 families have in common the presence of significant concentrations of leukocytes, and these cells are important in the local cleaning and immune regulation of the wound healing process. The main difference between them is the fibrin architecture, and this parameter considerably influences the healing potential and the therapeutical protocol associated to each platelet concentrate technology. In this article, we describe the historical evolutions of these techniques from the fibrin glues to the current L-PRP and L-PRF, and discuss the important functions of the platelet growth factors, the leukocyte content and the fibrin architecture in order to optimize the numerous potential applications of these products in regenerative medicine of the skin. Many outstanding perspectives are appearing in this field and require further research.

Current Knowledge and Perspectives for the Use of Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF) in Oral and Maxillofacial Surgery Part 2: Bone Graft, Implant and Reconstructive Surgery

Platelet concentrates for surgical use are innovative tools of regenerative medicine, and were widely tested in oral and maxillofacial surgery. Unfortunately, the literature on the topic is contradictory and the published data are difficult to sort and interpret. In bone graft, implant and reconstructive surgery, the literature is particularly dense about the use of the various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte- and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In this second article, we describe and discuss the current published knowledge about the use of PRP and PRF during implant placement (particularly as surface treatment for the stimulation of osseointegration), the treatment of peri-implant bone defects (after peri-implantitis, during implantation in an insufficient bone volume or during immediate post-extraction or post-avulsion implantation), the sinuslift procedures and various complex implant-supported treatments. Other potential applications of the platelet concentrates are also highlighted in maxillofacial reconstructive surgery, for the treatment of patients using bisphosphonates, anticoagulants or with post-tumoral irradiated maxilla. Finally, we particularly insist on the perspectives in this field, through the description and illustration of the use of L-PRF (Leukocyte- and Platelet-Rich Fibrin) clots and membranes during the regeneration of peri-implant bone defects, during the sinus-lift procedure and during complex implant-supported rehabilitations. The use of L-PRF allowed to define a new therapeutic concept called the Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges at the gingival and bone levels. As it is illustrated in this article, the NBR principles allow to push away some technical limits of global implant-supported rehabilitations, particularly when combined with other powerful biotechnological tools: metronidazole solution, adequate bone substitutes and improved implant designs and surfaces (for example here AstraTech Osseospeed or Intra-Lock Ossean implants). As a general conclusion, we are currently living a transition period in the use of PRP and PRF in oral and maxillofacial surgery. PRPs failed to prove strong strategic advantages that could justify their use in daily practice, and the use of most PRP techniques will probably be limited to some very specific applications where satisfactory results have been reached. Only a few simple, inexpensive and efficient techniques such as the L-PRF will continue to develop in oral and maxillofacial surgery in the next years. This natural evolution illustrates that clinical sciences need concrete and practical solutions, and not hypothetical benefits. The history of platelet concentrates in oral and maxillofacial surgery finally demonstrates also how the techniques evolve and sometimes promote the definition of new therapeutical concepts and clinical protocols in the today's era of regenerative medicine.

The Future of Platelet Concentrates in Sports Medicine: Platelet-Rich Plasma, Platelet-Rich Fibrin, and the Impact of Scaffolds and Cells on the Long-term Delivery of Growth Factors

Platelet concentrates for musculoskeletal injuries are innovative tools for regenerative medicine. Some interesting preliminary results have been described in sports medicine, yet little is known about the respective biological properties of the many different products available. Techniques have been classified into 4 main families with different fibrin architecture and cellular content and thus with different potential clinical applications. The pure platelet-rich plasma (P-PRP) and leukocyte- and platelet-rich plasma (L-PRP) are platelet suspensions, respectively, without and with leukocytes that can be used as liquid injectable preparations in injured tendons or articulations. In an open surgical site, these products can be activated into a fibrin gel that offers additional local antihemorrhagic and sealing properties. On the contrary, the pure platelet-rich fibrin (P-PRF) and leukocyte- and platelet-rich fibrin (L-PRF) are solid fibrin-based products, respectively, without and with leukocytes, which can be used as bioactive healing biomaterials in a surgical site. In this article, the significant differences between the numerous available products are emphasized. The comparison of the slow release of some key growth factors and coagulation/matrix proteins from L-PRF and P-PRP gel (preparation rich in growth factors [PRGF]) membranes during 7 days in vitro shows the different biological signatures of these 2 families of products and indicates that each technique should be fully characterized before investigating their potential clinical effects. If injectable platelet suspensions are to be beneficial in sports medicine as regenerative cocktails, it is important to remember that all platelet concentrates are in fact blood-based engineered tissues, and their effects are therefore much more complex to control than a classic pharmacologic treatment. The use of solid scaffolds for the long-term delivery of growth factors is a new approach, particularly the use of L-PRF as a regenerative in situ tissue engineering method during the treatment of tendinopathies of the quadriceps and the patellar tendon and for regenerative stimulation in rotator cuff repair or in anterior cruciate ligament repair. Finally, the future of these technologies in sports medicine requires an understanding of these complex materials, the engineering of the adequate regenerative material on demand, and knowledge of how to use them in the clinical situation.