Sprifermin treatment enhances cartilage integration in an in vitro repair model

Abstract

Cartilage integration remains a clinical challenge for treatment of focal articular defects. Cartilage exhibits limited healing capacity that declines with tissue maturation. Many approaches have been investigated for their ability to stimulate healing of mature cartilage or integration of repair tissue or tissue-engineered constructs with native cartilage. Growth factors present in immature tissue may enhance chondrogenesis and promote integrative repair of cartilage defects. In this study, we assessed the role of one such factor, fibroblast growth factor 18 (FGF18). Studies using FGF18 have shown a variety of positive effects on cartilage, including stimulation of chondrocyte proliferation, matrix biosynthesis, and suppression of proteinase activity. To explore the role of FGF18 on cartilage defect repair, we hypothesized that treatment with recombinant human FGF18 (sprifermin) would increase matrix synthesis in a defect model, thus improving integration strength. To test this hypothesis, 6 mm cartilage cylinders were harvested from juvenile bovine knees. A central 3 mm defect was created in each explant, and this core was removed and replaced. Resulting constructs were cultured in control or sprifermin-containing medium (weekly 24-h exposure of 100 ng/ml sprifermin) for 4 weeks. Mechanical testing, biochemical analysis, micro-CT, scanning electron microscopy, and histology were used to assess matrix production, adhesive strength, and structural properties of the cartilage-cartilage interface. Results showed greater adhesive strength, increased collagen content, and larger contact areas between core and annular cartilage in the sprifermin-treated group. These findings present a novel treatment for cartilage injuries that have potential to enhance defect healing and lateral cartilage-cartilage integration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2648-2656, 2018.

Human Recombinant Fibroblast Growth Factor-18 (Sprifermin), Enhances Cartilage Healing in a Cartilage Injury Model

“…In the present study, using an equine animal model we demonstrated that applying sprifermin in conjunction of microfracture treatment can improve the outcome of the surgery. This result is consistent with in vivo ndings in other animal models and in vitro and ex vivo studies that suggest an anabolic role for sprifermin in cartilage healing and hemostasis [21,29,30,34,43].…”

“…In vitro experiments utilizing sprifermin have demonstrated an improvement in collagen type II:I ratio and hyaline cartilage matrix formation and revealed a "hit and run" mode of action for sprifermin [29]. In an ex vivo study, Sennet and colleagues showed sprifermin can increase collagen content and adhesive strength leading to better cartilage-cartilage integration and superior repair of a microfracture defect [30]. Sprifermin is currently in phase two of clinical trials for treatment of knee osteoarthritis.…”

Efficacy and safety of sprifermin injection for knee osteoarthritis treatment: a meta-analysis

“…Sprifermin is a potential disease-modifying OA drug for KOA [ 3 , 9 ]. Previous in vitro studies suggested its enhancement in chondrocyte proliferation and overall extracellular matrix production, as well as an increased repair response of mechanically damaged articular cartilage [ 10 , 24 ]. The data in the included RCT studies demonstrated that sprifermin has a beneficial effect on cartilage thickness, volume, and morphology in KOA patients, with the effect appearing to be location-specific.…”

Self-assembled monolayers of phosphonates promote primary chondrocyte adhesion to silicon dioxide and polyvinyl alcohol materials

“…[36] While other cells types have been studied, the response of primary chondrocytes to SAMP modified surfaces has not been analyzed. Given the ongoing efforts to engineer the interface between scaffolds/ implants and host articular cartilage into which they are implanted, [56][57][58] the potential application of SAMPs to encourage chondrocyte adhesion is of translational relevance in the field of orthopaedic surgery. SAMP coatings were applied to both SiO 2 and PVA materials.…”