Enhancing Solute Transport in Immature Cartilage and Engineered Tissue Constructs

Abstract:

Osteoarthritis (OA) is a debilitating degenerative disease thatafflicts an estimated 27 million Americans age 25 and older.  Thisdisease leads to the progressive degradation of the articular layers ofdiarthrodial joints, significantly compromising the main function ofcartilage as a load bearing material, leading to pain and limitingactivities of daily living.  Cartilage functional tissue engineering isa highly promising technology that aims to provide a biologicalreplacement to worn articular layers, as a modality that considerablyexpands the limited options in the treatment of this disease.  Thoughcartilage degeneration is occasionally limited to small focal areaswithin articular layers, OA generally becomes symptomatic whendegradation has spread over much greater surface areas (such as greaterthan 25 percent of the articular layer). Unfortunately, functionaltissue engineering of large cartilage constructs is significantlyconstrained by the balance of nutrient transport and
consumption.  Several studies have shown that matrix deposition andelaboration of functional properties preferentially occurs near theperiphery of constructs, where nutrient supply from the surroundingculture medium is most abundant, whereas cells in the interior receiveless nutrients and produce less matrix, with poorer functionalproperties. In this presentation, we show that dynamic mechanicalloading can enhance
solute transport by up to an order of magnitude, and this enhancementcan be considerably accelerated by placing channels in the constructs.