Additive effects of type II collagen and hyaluronic acid on cartilage regeneration: An in vivo experimental study in a rat model

Abstract

Objective: Due to its avascular nature, cartilage tissue has a markedly limited capacity for self-repair. This study aimed to comparatively evaluate, in a histopathological context, the effects of type II collagen and hyaluronic acid-administered individually and in combination-on cartilage repair in an experimentally induced rat knee cartilage defect model. Materials and methods: Thirty-two male Wistar albino rats were randomly allocated into four groups: (1) microfracture only, (2) microfracture plus hyaluronic acid, (3) microfracture plus type II collagen, and (4) microfracture plus combined hyaluronic acid and type II collagen. All animals underwent a standardized microfracture procedure, followed by intra-articular injection of the assigned agent(s). At the end of the experimental period, histopathological evaluations were performed using the Mankin and O'Driscoll scoring systems. Results: Histological analysis demonstrated that the combination of type II collagen and hyaluronic acid yielded significantly superior outcomes in terms of tissue integrity, cellular organization, and extracellular matrix architecture compared with either agent alone (p < 0.05). While the type II collagen group also exhibited marked improvement, it did not achieve the same degree of repair as the combination group. Conclusion: The concomitant administration of type II collagen and hyaluronic acid exerts an additive effects in promoting cartilage regeneration. These findings highlight the potential of combined biomolecular strategies in intra-articular cartilage repair and provide a promising foundation for future investigations. © 2025 The Authors