Inflammation-modulating elastic decellularized extracellular matrix scaffold promotes meniscus regeneration

Scaffold-guided meniscus repair and regeneration show promise for meniscus injuries. Desirable scaffold properties are key to promoting proper tissue remodeling and effective regeneration. Herein, we report an inflammation-modulating elastic decellularized extracellular matrix (ECM) scaffold and evaluate its biological performance on meniscus repair in a rabbit model. An elastic scaffold of decellularized meniscus ECM (dmECM) was first prepared and functionalized with chitosan (CS) and ibuprofen (IBU) to obtain dmECM/CS-IBU scaffold. Our results show that CS and IBU grafting did not affect the overall properties of the dmECM/CS-IBU scaffold, including porous structure, good mechanical strength and elasticity. It promoted chondrocyte proliferation and preserved chondrogenic properties. In addition, both in vitro and in vivo assessments indicate that the dmECM/CS-IBU scaffold showed good anti-inflammatory properties and promoted pro-healing polarization of macrophages. In a partial rabbit meniscus defect model, the dmECM/CS-IBU scaffold showed promotive effects on in situ meniscus repair and preserved cartilage tissue. Therefore, our study provides a feasible strategy for fabricating scaffolds with tissue-specific bioactivity and inflammation-modulating abilities that synergistically promote meniscus repair and regeneration.

Statement of significance

Desirable scaffold properties are key to promoting proper tissue remodeling and effective regeneration of meniscus injuries. Herein, elastic decellularized scaffolds were prepared using natural meniscus and successfully grafted with chitosan and the anti-inflammatory drug ibuprofen (dmECM/CS-IBU). The dmECM/CS-IBU scaffold showed a pro-proliferative and phenotype- preserving effect on chondrocytes. In both in vitro and in vivo models, dmECM/CS-IBU scaffolds exhibited wonderful anti-inflammatory activity. In a meniscus white zone defect model, the dmECM/CS-IBU scaffold demonstrated in situ repair of tissue and protection of cartilage tissue. Therefore, we provides a feasible strategy for fabricating scaffolds with tissue-specific bioactivity and inflammation-modulating abilities that synergistically promote meniscus repair and regeneration.