Bioactive Microsphere-Based Scaffolds Containing Decellularized Cartilage

Abstract

The aim of this study was to fabricate mechanically functional microsphere-based scaffolds containing decellularized cartilage (DCC), with the hypothesis that this approach would induce chondrogenesis of rat bone marrow-derived mesenchymal stem cells (rBMSCs) in vitro. The DCC was derived from porcine articular cartilage and decellularized using a combination of physical and chemical methods. Four types of scaffolds were fabricated: poly(d,l-lactic-co-glycolic acid) (PLGA) only (negative control), TGF-β-encapsulated (positive control), PLGA surface coated with DCC, and DCC-encapsulated. These scaffolds were seeded with rBMSCs and cultured up to 6 weeks. The compressive modulus of the DCC-coated scaffolds prior to cell seeding was significantly lower than all other scaffold types. Gene expression was comparable between DCC-encapsulated and TGF-β-encapsulated groups. Notably, DCC-encapsulated scaffolds contained 70% higher glycosaminoglyan (GAG) content and 85% more hydroxyproline compared to the TGF-β group at week 3 (with baseline levels subtracted out from acellular DCC scaffolds). Certainly, bioactivity was demonstrated in eliciting a biosynthetic response from the cells with DCC, although true demonstration of chondrogenesis remained elusive under the prescribed conditions. Encapsulation of DCC appeared to lead to improved cell performance relative to coating with DCC, although this finding may be a dose-dependent observation. Overall, DCC introduced via microsphere-based scaffolds appears to be promising as a bioactive approach to cartilage regeneration, although additional studies will be required to conclusively demonstrate chondroinductivity.