Hydrogel-hydroxyapatite-monomeric collagen type-I scaffold with low-frequency electromagnetic field treatment enhances osteochondral repair in rabbits

Jiyuan Yan,Yingchi Zhang,Xiangyu Tang,Gaohong Sheng,Yongzhuang Ma,Chang Tu,Hua Wu,Chaoxu Liu,Ruizhuo Zhang,Hao Li,Huaixi Wang

doi:10.1186/s13287-021-02638-6

Abstract

BackgroundCartilage damage is a common medical issue in clinical practice. Complete cartilage repair remains a significant challenge owing to the inferior quality of regenerative tissue. Safe and non-invasive magnetic therapy combined with tissue engineering to repair cartilage may be a promising breakthrough.MethodsIn this study, a composite scaffold made of Hydroxyapatite-Collagen type-I (HAC) and PLGA-PEG-PLGA thermogel was produced to match the cartilage and subchondral layers in osteochondral defects, respectively. Bone marrow mesenchymal stem cells (BMSC) encapsulated in the thermogel were stimulated by an electromagnetic field (EMF). Effect of EMF on the proliferation and chondrogenic differentiation potential was evaluated in vitro. 4 mm femoral condyle defect was constructed in rabbits. The scaffolds loaded with BMSCs were implanted into the defects with or without EMF treatment. Effects of the combination treatment of the EMF and composite scaffold on rabbit osteochondral defect was detected in vivo.ResultsIn vitro experiments showed that EMF could promote proliferation and chondrogenic differentiation of BMSCs partly by activating the PI3K/AKT/mTOR and Wnt1/LRP6/β-catenin signaling pathway. In vivo results further confirmed that the scaffold with EMF enhances the repair of osteochondral defects in rabbits, and, in particular, cartilage repair.ConclusionHydrogel-Hydroxyapatite-Monomeric Collagen type-I scaffold with low-frequency EMF treatment has the potential to enhance osteochondral repair.

Highlights

Articular cartilage is mainly composed of chondrocytes and the extracellular matrix (ECM), such as aggrecan and collagen type 2 (Col2) with complex hierarchical structure [1]
We explored the effect of sinusoidal electromagnetic field (EMF) (SEMF) on osteochondral repair combined with Bone marrow mesenchymal stem cells (BMSC)-based tissue engineering, especially cartilage regeneration, using the PLGA-Poly(ethylene glycol) (PEG)-PLGA thermogel, and its underlying molecular mechanisms
A composite scaffold was constructed using a Hydroxyapatite-Collagen type-I (HAC) and PLGA–PEG–PLGA thermogel, which matched with cartilage and subchondral layers in osteochondral defects, respectively

Summary

Introduction

Articular cartilage is mainly composed of chondrocytes and the extracellular matrix (ECM), such as aggrecan and collagen type 2 (Col2) with complex hierarchical structure [1]. Cartilage damage is a common medical issue caused by trauma, Yan et al Stem Cell Res Ther (2021) 12:572 aging, and disorders of cartilage itself and subchondral bone (including osteoarthritis, osteonecrosis, and osteochondritis dissecans) [3, 4]. Owing to the avascularity of cartilage and low metabolic activity of chondrocytes, such cartilage defects have limited capacity to heal spontaneously [5, 6]. The complete repair of hyaline cartilage remains a major challenge in clinical practice owing to the inferior quality of regenerative tissue [14, 15]. Cartilage damage is a common medical issue in clinical practice. Complete cartilage repair remains a significant challenge owing to the inferior quality of regenerative tissue. Safe and non-invasive magnetic therapy combined with tissue engineering to repair cartilage may be a promising breakthrough

Methods

Results

Discussion

Conclusion