Osteochondral scaffold combined with aligned nanofibrous scaffolds for cartilage regeneration

Abstract

Osteochondral defect repair poses a significant challenge in its reconstruction as the damage is presented in both articular cartilage and the underlying subchondral bone. Tissue engineering approaches have utilized various scaffolds in combination of stem cells and growth factors to regenerate the defect. Still a significant challenge remains in creating a scaffold structure that supports the proliferation and differentiation of bone marrow stromal cells (BMSCs) into chondrocytes and osteoblasts while providing the appropriate mechanical stability. The present manuscript reports the fabrication and characterization of a biphasic scaffold system derived from biodegradable polymers such as poly(lactic acid-glycolic acid) (PLGA) as a hard shell and polycaprolactone (PCL) a soft component. Collectively this biphasic scaffold was able to withstand physiological loads up to 10 000 cycles in a cyclic compressive test. The scaffold surface was decorated with PCL aligned nanofibers contacting chondroitin sulfate and hyaluronic acid and nanofibers were cross-linked via carbodiimide linkages to retain these bioactive molecules over the culture period. The present study aims to show the potential of these bioactive scaffolds for the repair of osteochondral defects. Scaffolds were characterized by Fourier transform infra-red spectroscopy, optical microscopy and cyclic compressive testing. Primary rat bone marrow stem cells were seeded onto scaffolds and cell proliferation and differentiation was evaluated using RTPCR and immunohistochemistry. RT-PCR indicated that the scaffold was able to stimulate the different regions of osteochondral tissue: collagen type II and aggrecan expression in the cartilage region and BMP-2 in the bone region. Similarly protein secretion with induced alignment was confirmed with immunofluorescence imaging. This novel hybrid scaffold shows promising results in the regeneration of cartilage tissue as well as the underlying subchondral bone.