Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl₂, 10% of autologous thrombin, 10% of a mixture of CaCl₂+ thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-β1, PDGF-AB, IL-1β, and TNF-α. PRP activated with CaCl₂, thrombin, and CaCl₂/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl₂/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF-β1that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl₂induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic.

Purpose: The aim of this review was to analyze the available evidence on the clinical application of this biological approach for the injective treatment of cartilage lesions and joint degeneration, together with preclinical studies to support the rationale for the use of platelet concentrates, to shed some light and give indications on what to treat and what to expect from intra‐articular injections of platelet‐rich plasma (PRP).Methods: All in vitro, in vivo preclinical and clinical studies on PRP injective treatment in the English language concerning the effect of PRP on cartilage, synovial tissue, menisci, and mesenchymal stem cells were considered. A systematic review on the PubMed database was performed using the following words: (platelet‐rich plasma or PRP or platelet concentrate or platelet lysate or platelet supernatant) and (cartilage or chondrocytes or synoviocytes or menisci or mesenchymal stem cells).Results: Fifty‐nine articles met the inclusion criteria: 26 were in vitro, 9 were in vivo, 2 were both in vivo and in vitro, and 22 were clinical studies. The analysis showed an increasing number of published studies over time. Preclinical evidence supports the use of PRP injections that might promote a favourable environment for joint tissues healing. Only a few high‐quality clinical trials have been published, which showed a clinical improvement limited over time and mainly documented in younger patients not affected by advanced knee degeneration.Conclusions: Besides the limits and sometimes controversial findings, the preclinical literature shows an overall support toward this PRP application. An intra‐articular injection does not just target cartilage; instead, PRP might influence the entire joint environment, leading to a short‐term clinical improvement. Many biological variables might influence the clinical outcome and have to be studied to optimize PRP injective treatment of cartilage degeneration and osteoarthritis.Level of evidence: IV.

Purpose: To analyse the modifications induced by two different platelet‐rich plasma (PRP) preparations on osteoarthritis (OA) synoviocytes, by documenting changes in gene expression of factors involved in joint physiopathology.Methods: OA synoviocytes were cultured for 7 days in medium with different concentrations of either P‐PRP (a pure platelet concentrate without leucocytes but with a limited number of platelets), L‐PRP (a higher platelet concentrate containing leucocytes) or platelet‐poor plasma (PPP). Gene expression of interleukin (IL)‐1beta, IL‐6, IL‐8/CXCL8, tumour necrosis factor alpha, IL‐10, IL‐4, IL‐13, metalloproteinase‐13, tissue inhibitor of metalloproteinase (TIMP)‐1, (TIMP)‐3, (TIMP)‐4, vascular endothelial growth factor, transforming growth factor beta1, fibroblast growth factor (FGF)‐2, hepatocyte growth factor (HGF), hyaluronic acid (HA) synthases (HAS)‐1, (HAS)‐2, and (HAS)‐3 was analysed by RT‐PCR. HA production was determined in culture supernatants by ELISA.Results: IL‐1β, IL‐8 and FGF‐2 were significantly induced by L‐PRP compared to both P‐PRP and PPP; HGF was down‐modulated by L‐PRP versus both P‐PRP and PPP, and an inverse dose–response influence was shown for all preparations. Expression level of TIMP‐4 was lower in the presence of L‐PRP compared with P‐PRP. HA production and HAS gene expression did not seem to be modulated by PRP.Conclusions: L‐PRP is able to sustain the up‐regulation of proinflammatory factors, (IL‐1beta, IL‐8 and FGF‐2), together with a down‐modulation of HGF and TIMP‐4 expression, two factors that have been recognized as anti‐catabolic mediators in cartilage, thus supporting the need to further optimize the PRP preparations to be applied in clinical practice.