Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study

Abstract

Among all joints affected, knee osteoarthritis has a prevalence of about 10% in men and 13% in women over 60 years old. Knee osteoarthritis has high economic and social costs and may have a devastating impact on patient quality of life. Treatment of symptomatic knee Osteoarthritis may involve oral or topical administration of non-steroidal anti-inflammatory drugs or intra-articular injection of corticosteroids. Recently, a novel injectable collagen formulation (ChondroGrid) consisting of bovine hydrolyzed <3 kDa type I collagen has been developed and is currently available on the market as an injectable medical device. The primary objective of this study was to investigate the in vitro and in vivo effects of ChondroGrid in treating knee osteoarthritis symptoms to assess its safety and performance. Viability and proliferation of ChondroGrid-exposed human chondrocytes derived from five donors were assessed through the Alamar Blue/CyQuant assays. Their expression of MMP1/MMP3 and TIMP1/TIMP3 was then assessed through RT-PCR and that of TGFβ1, IGF-I, and VEGF using ELISA assays. Shape and ECM deposition were assessed using the Bern score after a 28-day ChondroGrid exposure, and collagen deposition was assessed using immunostaining. Records of 20 patients affected by Kellgren Lawrence grade 1 to 4 knee osteoarthritis who received three 4mg/2mL ChondroGrid injections 2 weeks apart were then retrospectively assessed to compare VAS, Lequesne, and WOMAC scores collected before and 15, 45, and 225 days after the first injection. ChondroGrid had no effects on the markers under consideration, but induced type-II and inhibited type-I collagen deposition; the Bern score was higher when cells were cultured with ChondroGrid. Patients experienced a 44% Lequesne score and a 55% VAS at moving score reduction. All other scores decreased >70%. ChondroGrid may prompt chondrocytes to produce hyaline cartilage, prevent fibrous tissue formation, and be a safe and effective adjuvant to treat symptomatic knee osteoarthritis.