Microporous acellular extracellular matrix combined with adipose-derived stem cell sheets as a promising tissue patch promoting articular cartilage regeneration and interface integration.

Abstract

Acute or chronic injury of articular cartilage leads to localized destruction. Difficulties with interface integration between the implant and native cartilage tissue can lead to an undesirable outcome. To improve cartilage repair and interface integration, we explored the therapeutic efficacy of microporous acellular extracellular matrix (ECM) combined with adipose-derived stem cell (ASC) sheets. Methods for fabricating ASC sheets and microporous acellular ECM were explored before transplanting the constructed ASC sheet/matrix in vivo and in vitro, respectively. After the operation, distal femur samples were collected at 6 and 12 weeks for further analysis. The decellularization process removed 90% of the DNA but retained 82.4% of glycosaminoglycans (GAGs) and 82.8% of collagen, which are the primary components of cartilage matrix. The acellular matrix/ASC sheet construct treatment in vivo showed better interface integration, cartilage regeneration, and collagenous fiber arrangement, which resembles the native structure. There was a significant increase in GAG and collagen accumulation at the zone of regeneration and integration compared to other groups. Gene expression analysis showed that the mRNA level associated with cartilage formation significantly increased in the acellular matrix/ASC sheet group (p<0.05), which is consistent with the histological analysis. ASC sheets promote interface integration between the implant and native tissue. This effect, together with the acellular matrix as a graft, is beneficial for cartilage defect repair, which suggests that acellular matrix/ASC sheet bioengineered cartilage implants may be a better approach for cartilage repair due to their enhanced integration.