Sabino Padilla

A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

PURPOSEnThis multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis.nnnMETHODSnWe randomly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis). The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As secondary outcomes, we also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety.nnnRESULTSnThe mean age of the patients was 59.8 years, and 52% were women. Compared with the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher (95% confidence interval, 0.5 to 27.6; P = .044). Regarding the secondary outcome measures, the rate of response to PRGF-Endoret was higher in all cases, although no significant differences were reached. Adverse events were mild and evenly distributed between the groups.nnnCONCLUSIONSnPlasma rich in growth factors showed superior short-term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee.nnnLEVEL OF EVIDENCEnLevel I, randomized controlled multicenter trial.

Comparison of Intra-Articular Injections of Plasma Rich in Growth Factors (PRGF-Endoret) Versus Durolane Hyaluronic Acid in the Treatment of Patients With Symptomatic Osteoarthritis: A Randomized Controlled Trial

PURPOSEnThe purpose of this study was to compare the efficacy and safety in a randomized, clinical trial of 3 injections of PRGF-Endoret (BTI Biotechnology Institute, Vitoria, Spain) versus one single intra-articular injection of Durolane hyaluronic acid (HA) (Q-MED AB, Uppsala, Sweden) as a treatment for reducing symptoms in patients with knee osteoarthritis (OA).nnnMETHODSnNinety-six patients with symptomatic knee OA were randomly assigned to receive PRGF-Endoret (3 injections on a weekly basis) or one infiltration with Durolane HA. The primary outcome measures were a 30% decrease and a 50% decrease in the summed score for the pain, physical function, and stiffness subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne scores from baseline to weeks 24 and 48. The percentage of OMERACT-OARSI (Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative) responders was also documented. As secondary outcomes, pain, stiffness, and physical function by use of the WOMAC and the Lequesne score were considered and overall safety of the injection themselves.nnnRESULTSnThe mean age of the patients was 63.6 years. Treatment with PRGF-Endoret was significantly more efficient than treatment with Durolane HA in reducing knee pain and stiffness and improving physical function in patients with knee OA. The rate of response to PRGF-Endoret was significantly higher than the rate of response to HA for all the scores including pain, stiffness, and physical function on the WOMAC, Lequesne index, and OMERACT-OARSI responders at 24 and 48 weeks. Adverse events were mild and evenly distributed between the groups.nnnCONCLUSIONSnOur findings show that PRGF-Endoret is safe and significantly superior to Durolane HA in primary and secondary efficacy analysis both at 24 and 48 weeks; provides a significant clinical improvement, reducing patients pain and improving joint stiffness and physical function with respect to basal levels in patients with knee OA; and should be considered in the treatment of patients with knee OA.

Leukocyte Inclusion within a Platelet Rich Plasma-Derived Fibrin Scaffold Stimulates a More Pro-Inflammatory Environment and Alters Fibrin Properties

One of the main differences among platelet-rich plasma (PRP) products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF) and leukocyte-platelet rich plasma (L-PRP) scaffolds was determined by enzyme-linked immunosorbent assay (ELISA) and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions.

A biological therapy to osteoarthritis treatment using platelet-rich plasma

Introduction: Osteoarthritis (OA) is a degenerative disease affecting the synovial joint. It is caused by cells exposure to non-physiological stimuli, either mechanical or biochemical, and the loss of bone-cartilage homeostasis. Some of these changes, however, may be reversed by the use of single or combined growth factors, suggesting that the treatment of OA could be addressed using a pool of growth factors. Areas covered: This review addresses current molecular and biological knowledge and implicates the recapitulation of some developmental processes during endochondral ossification in OA aetiology and pathogenesis. Platelets act as carriers of endogenous morphogens that may modulate cell fate and therefore affect joint tissues structure and function. We shed light on the platelet-rich plasma effects on biological level that might drive the osteoarthritic joints improvement both in structure and function. Expert opinion: We present the therapeutic potential of plasma rich in growth factors (PRGF-Endoret), an endogenous biological therapy that might modulate the gene expression of cells such as chondrocytes, synoviocytes, macrophages, and mesenchymal stem cells, and thereby influence an anabolic microenvironment of synovial joint which is conducive to maintaining the homeostatic state of the joints tissues, and hence reduce pain and improve the joint motion.

A new strategy to tackle severe knee osteoarthritis: Combination of intra-articular and intraosseous injections of Platelet Rich Plasma

ABSTRACT Introduction: Knee osteoarthritis (KOA) is a mechanically induced, cytokine and enzyme-mediated disorder involving all the joint tissue of the knee. Rebuilding a physiological-homeostatic network at the tissue level following knee organ failure, such as in severe KOA, is a daunting task with therapeutic targets encompassing the articular cartilage, synovium and subchondral bone. Intraarticular infiltration of plasma rich in growth factors (PRP) has emerged as a promising symptomatic approach, although it is insufficient to reach the subchondral bone. Areas covered: This review addresses current molecular and cellular data in joint homeostasis and osteoarthritis pathophysiology. In particular, it focuses on changes that subchondral bone undergoes in knee osteoarthritis and evaluates recent observations on the crosstalk among articular cartilage, subchondral bone and synovial membrane. In addition, we review some mechanistic aspects that have been proposed and provide the rationale for using PRP intraosseously in KOA. Expert opinion: The knee joint is a paradigm of autonomy and connectedness of its anatomical structures and tissues from which it is made. We propose an innovative approach to the treatment of severe knee osteoarthritis consisting of a combination of intraarticular and intraosseous infiltrations of PRP, which might offer a new therapeutic tool in KOA therapy.

Ultrasound-guided plasma rich in growth factors injections and scaffolds hasten motor nerve functional recovery in an ovine model of nerve crush injury.

In the present study we evaluated the motor recovery process of peripheral nerve injury (PNI), based on electrophysiological and histomorphometric criteria, after treatment with plasma rich in growth factors (PRGF) injections and scaffolds in an ovine model. Three groups of sheep underwent a nerve crush lesion: the first group (nu2009=u20093) was left to recover spontaneously (SR); the second group was administered saline injections (SI; nu2009=u20095) and a third group (nu2009=u20096) received PRGF injections and scaffolds immediately after the crush injury. At post‐intervention week 8, 70% of sheep in the PRGF group were CMAP‐positive, with no electrophysiological response in the rest of the groups. Histomorphometric analysis 12u2009weeks after the surgical intervention revealed that the average axonal density of the SR (1184u2009±u2009864 axons/µm2) and SI (3109u2009±u20092450 axons/µm2) groups was significantly inferior to the control (8427u2009±u20092433 axons/µm2) and also inferior to the PRGF group (5276u2009±u20094148 axons/µm2), showing no significant differences between the control and PRGF groups. The axonal size of the SR and SI groups was significantly smaller compared with the control group (18u2009±u20094u2009µm2), whereas the axonal size of the PRGF group (6u2009±u20095u2009µm2) did not show statistical differences from the control. Morphometry of the target muscles indicated that the PRGF group had the lowest percentage volume reduction 12u2009weeks after the crush injury. The PRGF group had larger muscle fibre areas than the SI and SR groups, although the differences did not reach statistical significance. Overall, these data suggest that the PRGF injections and scaffolds hastened functional axon recovery and dampened atrophy of the target muscles in an ovine model. Copyright

Muscle repair: platelet-rich plasma derivates as a bridge from spontaneity to intervention.

Muscle injuries account for between 10% and 55% of all sporting injuries. Although the skeletal muscle is a plastic organ capable of responding efficiently to environmental changes, the appropriate treatment of muscle injuries remains a daunting clinical challenge in sports medicine. There is considerable evidence to indicate that growth factors, such as transforming growth factor-β (TGFβ), hepatocyte growth factor (HGF) or insulin-like growth factor (IGF), and fibrin matrix are key in cellular events required for muscle repair and regeneration, namely myogenesis, angiogenesis and fibrogenesis. An innovative biological approach to the treatment of muscle injuries is the application of Plasma Rich in Growth Factors (PRGF) in intramuscular infiltrations. PRGF delivers growth factors, cytokines and adhesive proteins present in platelets and plasma, as well as other biologically-active proteins conveyed by the plasma, such as fibrinogen, prothrombin and fibronectin. This autologous, mimetic biomaterial embedded with a pool of growth factors acts as a smart dynamic scaffold, and should be applied taking into account a biological approach. A clinical trial is required to assess the functional repair outcome of PRGF infiltrations in muscle injuries.

Platelet-rich plasma, a source of autologous growth factors and biomimetic scaffold for peripheral nerve regeneration

ABSTRACT Introduction: In mammals, axons of injured peripheral nerves (PNI) can and do regenerate, but often the functional recovery is incomplete or suboptimal. In recent years, in vivo tissue engineering approaches through molecular intervention and scaffolding are offering promising outcomes. Evidence is accumulating in both preclinical and clinical settings indicating that Platelet-rich plasma (PRP) and fibrin scaffolds obtained from this technology hold an important adjuvant therapeutic potential. Areas covered: This review addresses current molecular and cellular data in intrinsic nerve repair processes and describes different strategies to harness and enhance these processes by using biochemical and biomechanical cues. It focuses on autologous fibrin, plasma and platelet-derived growth factors as filler or scaffolds that can synergize with the gold standard therapy and other nerve guidance conduits. Expert opinion: PRP is applied as a filler of nerve conduits or vein-muscle grafts across nerve gaps post trauma by infiltrating the nerve stumps perineurally and intraneurally in neuropathies, or as scaffolds to bridge or wrap nerve stumps, with significant neurological recovery and pain reduction. The application of PRP at the injured nerve site might be considered as an ‘off the shelf’ alternative.

Intraosseous Infiltration of Platelet-Rich Plasma for Severe Knee Osteoarthritis

We describe a new technique of platelet-rich plasma (PRP) infiltration for the treatment of severe knee osteoarthritis. PRP intra-articular infiltration is a promising treatment for knee osteoarthritis, but it still has some limitations in high-degree osteoarthritis. Diagnosis of osteoarthritis is based on clinical and radiographic findings, and patients with grade III or IV knee tibiofemoral osteoarthritis based on the Ahlbäck scale are considered candidates for this technique. The technique consists of performing intraosseous infiltration of PRP into the subchondral bone, which acts on this tissue and consequently on cartilage-bone communication. Although the intraosseous injection hinders the conventional knee intra-articular infiltration, it allows an extension of the range of action of the PRP, which acts directly on the subchondral bone, which is involved in the progression of osteoarthritis. Thus this technique involves a new administration of PRP that can delay knee arthroplasty; moreover, it can be applied for not only severe osteoarthritis but also other pathologies in which the subchondral bone is critical in the etiology, such as necrosis and osteochondral lesions.

Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery.