Fabrication of dual drug loaded bilayered chitosan based composite scaffolds as osteochondral substitutes and evaluation of in vitro cell response using the MC3T3 pre-osteoblast cell line

Abstract

Osteochondral defects are relatively common in weight-bearing joints of the lower extremities and require multiple approaches of treatment. This work is focused on designing three-dimensional (3D) bilayered scaffolds fully integrating a top chitosan/hydroxypropylmethyl cellulose layer (CS/HPMC) mimicking cartilage and a bottom chitosan/hydroxypropylmethyl cellulose/nano-hydroxyapatite layer (CS/HPMC/nHAp) imitating bone for the treatment of osteochondral defects prepared by freeze drying. Additionally, an anti-inflammatory drug (in the bottom layer) and an antibiotic drug (in the top layer) are incorporated in the form of microspheres and nanofibers, respectively, into these scaffolds to diminish/prevent post-surgical inflammation/infection through sustained release of the drugs. The scaffolds were characterized by a variety of techniques. FT-IR analysis confirmed that there is no/weak interactions between the components, SEM images showed that both layers of the scaffolds have homogenous pore distribution, and scaffolds exhibited reproducible swelling and degradation behavior. Drug release was shown to take place over a period of 14 days in PBS. The scaffolds supported the growth and proliferation of MC3T3 pre-osteoblast cells in vitro and have potential for use in vivo application in the future.