Human early mesenchymal stromal cells delivered on porous lightweight biodegradable polycaprolactone-based microcarriers result in improved cartilage formation

Abstract

Porous lightweight polycaprolactone (LPCL)-based microcarriers (MC) can be used for large-scale production of human mesenchymal stromal cells (MSC) in stirred bioreactors. These biodegradable MC can serve in delivering MSC, which exhibit improved bone healing in a rat calvarial defect model. Therefore, this study aims to explore their use as scaffolds to create chondrogenically differentiated, MSC-laden LPCL MC constructs for cartilage formation in vitro and in vivo in a rabbit osteochondral defect model. In-vitro studies, defining critical parameters that resulted in efficient chondrogenic differentiation of MSC expanded on the surface of LPCL MC were performed. The optimized MSC-LPCL MC constructs were transplanted in a rabbit osteochondral defect model and evaluated after 5 months, with histological staining and scoring. Our in vitro studies demonstrate that about 4.7 × 103 porous LPCL MC seeded with 50 × 103 cells at early exponential growth phase (21% cell confluency) resulted in the best MSC-PCL MC construct, with efficient cell growth and chondrogenic differentiation, after 21 days. Implantation of chondrogenically differentiated MSC-LPCL MC constructs resulted in the best cartilage healing outcomes: (i) 75% of samples (6 out 8 defects) displaying good healing outcomes, (ii) the greatest histological score at 22 ± 7 and 26 ± 7 (without and with subchondral bone evaluation respectively), and (iii) the highest mean score for 8 out of 12 categories, as compared to other transplant groups. This is the first study demonstrating that chondrogenically differentiated MSC-LPCL MC constructs can induce the most efficient cartilage healing in rabbits with an osteochondral defect.