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

Abstract

Background & Aim Porous polycaprolactone (PCL)-based microcarriers (MC) can be used for large-scale production of human mesenchymal stromal cells (MSC) in stirred bioreactors. These biodegradable MC can deliver MSC, which improved bone healing in a rat calvarial defect model. Hence, this study aims to explore their use as scaffolds to create chondrogenically differentiated, MSC-laden PCL MC constructs for cartilage formation in vitro and in vivo in a rabbit endochondral defect model. Methods, Results & Conclusion Design: In vitro studies defining critical parameters that resulted in efficient chondrogenic differentiation of MSC expanded on the surface of PCL MC were performed. The optimized, critically-defined MSC-PCL MC constructs were transplanted in a rabbit endochondral defect model and evaluated after 5 months with histological staining and scoring. In vitro studies demonstrate that about 4.7 × 10 3 porous PCL MC seeded with 50 × 10 3 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-PCL MC constructs resulted in the best cartilage healing outcomes: (i) 75% of samples 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-PCL MC constructs can induce the most efficient cartilage healing in rabbits with endochondral defect.