Interstitial Flow Produces a Superficial Zone-Like Layer in Tissue Engineered Cartilage

INTRODUCTION: Surgical repair of articular cartilage typically yields fibrocartilage that lacks the stratified ECM architecture of native cartilage and does not integrate with the surrounding hyaline cartilage. Because of these limitations, there has been considerable interest in cartilage tissue engineering and that led to the development of various bioreactor systems to grow functional engineered cartilage constructs for in vivo implantation. Some of these bioreactors have used mechanical stimulation to enhance the synthetic activity of the cells [1] while others have used perfusion fluid flow to enhance nutrient transport and produce homogenous constructs [2]. To date, however, recapitulation of the zonal organization of native cartilage and the associated anisotropy in structure and mechanical properties in engineered constructs remains elusive [3]. We hypothesize that in addition to improving nutrients’ transport via convection, interstitial fluid flow induces frictional drag and shear stress that can affect the alignment of fibrillar collagen in the constructs. To test this hypothesis, we investigated the effects of Poiseuille flow-induced interstitial flow fields on ECM production and collagen alignment and spatial heterogeneity in chondrocyte-seeded agarose hydrogel in a parallel plate bioreactor.