Three-dimensional polycaprolactone scaffold-conjugated bone morphogenetic protein-2 promotes cartilage regeneration from primary chondrocytes in vitro and in vivo without accelerated endochondral ossification

摘要

As articular cartilage is avascular, and mature chondrocytes do not proliferate, cartilage lesions have a limited capacity for regeneration after severe damage. The treatment of such damage has been challenging due to the limited availability of autologous healthy cartilage and lengthy and expensive cell isolation and expansion procedures. Hence, the use of bone morphogenetic protein-2 (BMP-2), a potent regulator of chondrogenic expression, has received considerable attention in cartilage and osteochondral tissue engineering. However, the exact role of BMP-2 in cartilage repair has been postulated to promote both cartilage formation and subsequent cartilage degradation through hypertrophy and endochondral ossification. Furthermore, it is likely that the manner in which BMP-2 is presented to chondrocytes will influence the physiologic pathway (repair vs. degeneration). This study investigates the relative influence of BMP-2 on cartilage matrix and potential subsequent bone matrix production using primary chondrocytes seeded on designed 3D polycaprolactone (PCL) scaffolds with chemically conjugated BMP-2. The results show that chemically conjugated BMP-2 PCL scaffolds can promote significantly greater cartilage regeneration from seeded chondrocytes both in vitro and in vivo compared with untreated scaffolds. Furthermore, our results demonstrate that the conjugated BMP-2 does not particularly accelerate endochondral ossification even in a readily permissible and highly vascular in vivo environment compared with untreated PCL scaffolds. This study not only reveals the potential use of the BMP-2 conjugation delivery method for enhanced cartilage tissue formation but also gives new insights for the effects of conjugated BMP-2 on cartilage regeneration and osteochondral ossification.