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

Paola De Luca,Michelangelo Beggio,Piero Volpi,Alessandra Colombini,Laura De Girolamo,Giulia Carimati

doi:10.3390/jcm8070975

Paola De Luca, Michelangelo Beggio + Show 4 more

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https://doi.org/10.3390/jcm8070975

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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 4 mg/2 mL 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.

Highlights

Osteoarthritis (OA) is the most common musculoskeletal disorder [1] affecting both small and large diarthrodial joints with the hand, hip, and knee being the most affected areas [2]
Records of 20 patients affected by Kellgren Lawrence grade 1 to 4 knee osteoarthritis who received three 4 mg/2 mL ChondroGrid injections 2 weeks apart were retrospectively assessed to compare VAS, Lequesne, and WOMAC scores collected before and 15, 45, and 225 days after the first injection
The in vitro results showed that CG negatively affects chondrocyte viability and proliferation at 1.5 mg/mL, a concentration that, given the therapeutic protocol proposed for CG and the volume of the synovial fluid in the symptomatic OA knee joint (>10 mL) [33,34], can never be reached in the clinical setting

Summary

Introduction

Osteoarthritis (OA) is the most common musculoskeletal disorder [1] affecting both small and large diarthrodial joints with the hand, hip, and knee being the most affected areas [2]. Topical application of NSAIDs calls for multiple daily application to show effectiveness, while oral NSAIDs administration and intra-articular corticosteroid injection have a short-term effect and exhibit several side-effects [7,8,9] This has led to investigations using non-pharmacological interventions alternatively to or in combination with pharmacological treatments [2,10], including manual and physical therapies [11] and viscosupplementation [12,13]. OA-affected joints exhibit a complex range of structural, tissue, cellular, and biochemical changes Inflammation mediators, such as IL-1α, IL-1β, TNF-β, and IL-6, are expressed and they, in turn, activate cartilage-degrading enzymes, such as matrix metalloproteinases (MMPs) and a disintegrin and a metalloproteinase with thrombospondin motifs (ADAMTS) [1,14]. The secondary purpose was to gain preliminary clinical information concerning CG safety and performance in reducing symptoms of knee OA through a pilot retrospective collection and analysis of clinical data

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