Preclinical Mechanistic Evaluation of Hyaluronan/Niacinamide (Vitamin B3) Hydrogels: Toward an Enhanced Viscosupplement System with Ancillary Anti-Arthritic Attributes

Journal article

Osteoarthritis (OA), a degenerative joint disease primarily affecting the hips and knees, is characterized by multifactorial dysregulation of chondrocyte homeostasis and currently lacks curative treatment options. Intra-articular hyaluronic acid (HA) injections have clinically provided symptomatic relief for three decades; however, HA's rapid in vivo degradation by free radicals and hyaluronidases limits its efficacy. We hypothesized that adding niacinamide (vitamin B3) to linear HA hydrogels would provide ancillary anti-inflammatory and anti-catabolic properties, thereby improving HA-based viscosupplementation therapy. This preliminary preclinical mechanistic study investigated the functional effects of incorporating niacinamide into linear HA-based hydrogels using in vitro cellular models. Initially, Raw 264.7 macrophages and C28/I2 or SW1353 human chondrocytes were pre-treated with varying concentrations of HA/B3, with or without lipopolysaccharide (LPS) or interleukin-1β (IL-1β), respectively. Subsequently, pro-inflammatory and pro-catabolic markers were quantified biochemically. Results demonstrated that HA/B3 hydrogels exhibited enhanced functional stability compared to HA alone and possessed significant anti-inflammatory and anti-catabolic properties, without inducing cytotoxicity in either cell line. In Raw 264.7 macrophages, HA/B3 inhibited LPS-induced tumor necrosis factor-α (TNF-α) release and suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression. In vitro, HA/B3 hydrogels reduced IL-1β-induced IL-6 production in primary chondrocytes by 16% and suppressed PGE2 concentration in both macrophages and chondrocytes by 60%, effects superior to HA alone. Finally, a rat primary articular chondrocyte model suggested slight anti-hypertrophic effects of HA/B3 in vitro. Collectively, these findings suggest that HA/B3 hydrogels possess anti-arthritic potential, highlighting a novel strategy for next-generation viscosupplement systems.

Authors: Hadjab, F; Antoine, S; Hamel, B; Benderdour, M; Fahmi, H

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: MDPI
• Journal: Bioengineering
• Volume: 12
• Issue: 11
• Pages: 1246
• Publication date: 2025-11-14
• Acceptance date: 2025-11-13
• DOI: 10.3390/bioengineering12111246
• EISSN: 2306-5354
• ISSN: 2306-5354
• Pmid: 41301202
• Language: English
• Keywords: Hyaluronic acid; Primary Chondrocytes; Niacinamide; Antioxidants; Osteoarthritis; Viscosupplements; Biophysical Properties; hydrogels; Degradation; Inflammation