SCIENTIFIC WORK AND DISSEMINATION

Plasma rich in growth factors (PRGF-Endoret) is an endogenous therapeutic technology that is gaining interest in regenerative medicine due to its potential to stimulate and accelerate tissue healing and bone regeneration. This autologous biotechnology is designed for the in situ delivery of multiple cellular modulators and the formation of a fibrin scaffold, thereby providing different formulations that can be widely used in numerous medical and scientific fields including dentistry, oral implantology, orthopedics, ulcer treatment and tissue engineering among others. Here we discuss the important progress that has been accomplished in this field. Furthermore, a comprehensive outlook of the intriguing therapeutic applications of this technology is presented.

Treating malignant brain tumors represents one of the most formidable challenges in oncology. Contemporary treatment of brain tumors has been hampered by limited drug delivery across the blood–brain barrier (BBB) to the tumor bed. Biomaterials are playing an increasingly important role in developing more effective brain tumor treatments. In particular, polymer (nano)particles can provide prolonged drug delivery directly to the tumor following direct intracerebral injection, by making them physiochemically able to cross the BBB to the tumor, or by functionalizing the material surface with peptides and ligands allowing the drug-loaded material to be systemically administered but still specifically target the tumor endothelium or tumor cells themselves.
Biomaterials can also serve as targeted delivery devices for novel therapies including gene therapy, photodynamic therapy, anti-angiogenic and thermotherapy. Nanoparticles also have the potential to play key roles in the diagnosis and imaging of brain tumors by revolutionizing both preoperative and intraoperative brain tumor detection, allowing early detection of pre-cancerous cells, and providing real-time, longitudinal, non-invasive monitoring/imaging of the effects of treatment.
Additional efforts are focused on developing biomaterial systems that are uniquely capable of delivering tumor-associated antigens, immunotherapeutic agents or programming immune cells in situ to identify and facilitate immune-mediated tumor cell killing. The continued translation of current research into clinical practice will rely on solving challenges relating to the pharmacology of nanoparticles but it is envisioned that novel biomaterials will ultimately allow clinicians to target tumors and introduce multiple, pharmaceutically relevant entities for simultaneous targeting, imaging, and therapy in a unique and unprecedented manner.

Endogenous regenerative technology (Endoret) involves the use of patient's own biologically active proteins, growth factors and biomaterial scaffolds for therapeutic purposes. This technology provides a new approach for the stimulation and acceleration of tissue healing and bone regeneration. The versatility and biocompatibility of using patient-derived fibrin scaffold as an autologous, biocompatible and biodegradable drug delivery system open the door to a personalized medicine that is currently being used in numerous medical and scientific fields including dentistry, oral implantology, orthopaedics, ulcer treatment, sports medicine and tissue engineering among others. This review discusses the state of the art and new directions in the use of endogenous technology in the repair and regeneration of injured tissues by means of a controlled and local protein and growth factor delivery. The next generations of engineering strategies together with some of the most interesting therapeutic applications are discussed together with the future challenges in the field

Biomaterials are likely to have an increasingly important role in the treatment of nervous system disorders. Recently developed biomaterials can enable and augment the targeted delivery of drugs or therapeutic proteins to the brain, allow cell or tissue transplants to be effectively delivered to the brain and help to rebuild damaged circuits. Similarly, biomaterials are being used to promote regeneration and to repair damaged neuronal pathways in combination with stem cell therapies. Many of these approaches are gaining momentum because nanotechnology allows greater control over material-cell interactions that induce specific developmental processes and cellular responses including differentiation, migration and outgrowth.

OBJECTIVES: Preparations rich in growth factors (PRGF) release them plus bioactive proteins at localized sites, with the aim of triggering healing and regenerative processes. The prevailing paradigm suggests that their influence on proliferation, angiogenesis and the extracellular matrix synthesis is minimal. However, variations in their composition and impact on different cell phenotypes have not been examined. MATERIALS AND METHODS: Sixteen fibroblast cultures obtained from three different anatomical sites (skin, synovium and tendon) of 16 donors were exposed to the molecular pool released from PRGF scaffolds, with increasing amounts of platelets. We evaluated cell proliferation, secretion of angiogenic growth factors (VEGF and HGF), synthesis of type I collagen and hyaluronic acid (HA), considering platelet dose and anatomical origin of the cells. Activity of transforming growth factor-beta (TGF-β) in type I procollagen and HA synthesis was examined by adding exogenous TGF-β to plasma preparations. RESULTS: All plasma preparations induced a significant proliferative response compared to non-stimulated cells (P < 0.05). Maximum proliferation rate was obtained with PRGF with 2-fold or 4-fold platelet concentration. Exposure to PRGF stimulated VEGF synthesis exclusively in tendon cells (P < 0.05), which also exhibited a different pattern of HGF production (P < 0.05). PRGF enhanced HA synthesis (P < 0.05), but did not alter collagen I production. Platelet-secreted TGF-β may be involved in HA, but not in type I procollagen synthesis. CONCLUSIONS: Optimizing composition and use of platelet-rich products is crucial to enhancing the therapeutic potential of this technology. Our data show that the biological effects of PRGF may depend on concentration of platelets and on the anatomical source of the cells.

Platelets help to prevent blood loss at sites of vascular injury. To do this, they adhere, aggregate and form a procoagulant surface leading to thrombin generation and fibrin formation. In addition, platelets express and release substances that promote tissue repair and influence processes such as angiogenesis, inflammation and the immune response. They contain secretable pools of a large number of biologically active proteins while newly synthesised active metabolites are also released. Although anucleate activated platelets possess a spliceosome and can synthesize tissue factor and interleukin-1b. The binding of secreted proteins within a developing fibrin mesh or to the extracellular matrix can create chemotactic gradients accelerating cell migration and differentiation as well as the recruitment of stem cells. The fact that platelets secrete biologically active proteins means that their applied use has a positive influence in clinical situations requiring rapid healing. Their administration in a fibrin clot provides an adhesive support that helps confine biological activity to a chosen site. Dental implant surgery, orthopaedic surgery, muscle and tendon repair, skin ulcers, hole repair in eye surgery and cardiac surgery are situations where the use of autologous platelets accelerates healing. We now review the ways in which platelets participate in these processes.

Trends in Pharmacological Science, with an impact factor close to 11, is one of the most important journals in the field of pharmacology and pharmacy. This journal kindly invited us to review the current situation of platelet rich products. The technology of preparation rich in growth factor (PRGF) aims to translate the therapeutic potential of the platelet and plasma derived growth factors and proteins to suitable and standardized formulations. Recent advances in the filed have enabled the therapeutic application of this technology in surgery and in the treatment of a wide range of medical disorders. This review highlights the important progress that has been accomplished in the field during the last few years. Additionally, recent advances in the stimulation and acceleration of tissue healing and bone regeneration obtained with PRGF technology are discussed.

Platelet-rich preparations constitute a relatively new biotechnology for the stimulation and acceleration of tissue healing and bone regeneration. The versatility and biocompatibility of this approach has stimulated its therapeutic use in numerous medical and scientific fields including dentistry, oral implantology, orthopaedics, ulcer treatment, tissue engineering among others. Here we discuss the important progress that has been accomplished in the field of platelet-rich preparations in the last few years. Some of the most interesting therapeutic applications of this technology are discussed as are some of the limitations, future challenges and directions in the field.

Autologous platelet-rich matrices can be an aid in surgery by promoting and accelerating tissue healing. In the present work we aimed to evaluate the potential role of the most abundant platelet secreted growth factors, transforming growth factor (TGFß1) and platelet-derived growth factor (PDGF), in tendon repair. Therefore we studied human tenocyte proliferation and maturation after exposing cells in culture to treatments differing by the presence or the lack of the bulk of platelet-secreted molecules. In the presence of the total pool of platelet-secreted molecules PDGF was a partial contributor to cell proliferation while exogenous TGF-ß1 acted as a negative modulator. The production of type I collagen was similar regardless of differences in the concentration of TGF-ß1. Moreover, addition of exogenous TGF-ß1 promoted a significant increase in collagen synthesis only in the absence of other platelet released substances. Interestingly, exogenous TGF-ß1 increased the synthesis of vascular endothelial growth factor (VEGF) and simultaneously abolished the production of hepatocyte growth factor (HGF). Furthermore, antibody-mediated neutralization of TGF-ß1 induced a decrease in VEGF synthesis and concomitantly a substantial production of HGF. All these data demonstrate that the balance between TGF-ß1 and the pools of platelet-secreted molecules may have important therapeutic implications in the control of angiogenesis and fibrosis.

A review with an impact factor of 8.5. In fact, it is the scientific article of highest impact that deals with the therapeutic possibilites of platelet-rich preparations and, more specifically, of PRGF®. The paper discusses the role of growth factors in bone healing and regeneration processes.to understand the therapeutic potential of preparations rich in platelets. This article assumes that the reader knows that PRGF® is a type of platelet-rich preparation; it presents characteristics very different from other existing preparations on the market, such as the absence of white blood cells and thrombin and a moderate concentration of platelets that make PRGF® an optimized, standardized and biologically safer product. Different therapeutic possibilities of PRGF® are also enumerated: bone and soft tissue regeneration, tissue engineering, cellular therapy, and others.

This is a widely circulated journal in the biomaterials and tissue engineering field and has a 3.7 impact factor. In this work, we and our colleagues studied and compared the proliferation and the synthesis of type I collagen and angiogenic factors in human tenocytes cultured in a PRGF® matrix and a platelet-poor matrix. The results show that the PRGF® induces greater cellular proliferation and a better synthesis of VEGF (the principal angiogenic factor). Also, the cell cultures stimulated with PRGF® secreted HGF (anti-fibrotic factor) and some type I collagen. When injected in sheep, PRGF® increased cellular density and promoted angiogenesis without exhibiting side effects or fibrosis.

In this study, the potential of the growth factors liberated from PRGF® in tendon healing and regeneration were evaluated. Levels of PDGF, TGF-ß1, IGF-I, VEGF, HGF and EGF were measured in the supernatants of a platelet-rich preparation (PRGF®), a platelet-poor preparation (PPP) and an unactivated platelet-poor preparation and the effect of the pool of factors in human tenocytes. The tenocytes proliferated as a response to PRGF® and PPP, but not to unactivated PPP. Moreover, the cells secreted HGF and VEGF due to the effect of the PPP and, in larger measure, to the PRGF®. Our results demonstrate that PRGF® induces the proliferation of the tenocytes and the synthesis of a potent angiogenic factor such as VEGF and a potent anti-fibrotic factor like HGF.

This review article delves more deeply into the functions and principal features of platelets, emphasizing their role as a reservoir of a large number of growth factors with therapeutic potential. The internal and external structure of platelets is described in what are referred to as transcellular receptors as well as intracellular granules. The existing biological mediators in the granules liberated once the platelets are activated are also enumerated in detail. Finally, specific cases are presented in which the platelets play a fundamental role; and, therefore, their use can lead to significant therapeutic benefits, such as for orthopedic surgery, ulcer and wound healing, tendon and ligament repair, plastic and reconstructive surgery, etc.