Composite Scaffold for Osteochondral Interface Tissue Engineering

INTRODUCTION: Osteoarthritis is the leading cause of physical disability among Americans, and tissue engineered osteochondral grafts have emerged as a promising treatment option for this debilitating condition. Currently, the formation of a stable interface between the cartilage and bone portions of the osteochondral graft remains a significant challenge[1]. Articular cartilage integrates with bone via the osteochondral interface, which consists of an interdigitated calcified cartilage region that separates the uncalcified, deep-zone cartilage layer from subchondral bone[2]. Regeneration of this soft tissue-to-bone interface will be critical for promoting the integration of osteochondral grafts, and thereby extending their clinical functionality[1]. This study describes a composite hydrogel scaffold of hydroxyapatite (HA) and agarose for calcified cartilage formation. Agarose has been successfully utilized for functional cartilage tissue engineering both in vitro and in vivo[3,4]. Inclusion of HA as a substrate phase for interface formation is advantageous as it resembles the mineral of the calcified cartilage layer. At the interface, aggregates of HA platelets instead of individual crystals are observed[5]. Therefore, the objective of this study is to determine the potential of composite HA-agarose scaffold for interface regeneration. Specifically, we will 1) examine the effect of HA presence and particle size and 2) determine the effects of triiodothyronine (T3), a known promoter of hypertrophy[4] on deep zone chondrocyte (DZC) proliferation, matrix deposition, and mineralization in the hydrogel+HA scaffold. It is hypothesized that T3 stimulation will promote DZC hypertrophy and calcification, and moreover, DZC response will be a function of HA particle size.