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Abstract:
Osteoarthritis (OA) is a debilitating degenerative disease that
afflicts an estimated 27 million Americans age 25 and older. This
disease leads to the progressive degradation of the articular layers of
diarthrodial joints, significantly compromising the main function of
cartilage as a load bearing material, leading to pain and limiting
activities of daily living. Cartilage functional tissue engineering is
a highly promising technology that aims to provide a biological
replacement to worn articular layers, as a modality that considerably
expands the limited options in the treatment of this disease. Though
cartilage degeneration is occasionally limited to small focal areas
within articular layers, OA generally becomes symptomatic when
degradation has spread over much greater surface areas (such as greater
than 25 percent of the articular layer). Unfortunately, functional
tissue engineering of large cartilage constructs is significantly
constrained by the balance of nutrient transport and
consumption. Several studies have shown that matrix deposition and
elaboration of functional properties preferentially occurs near the
periphery of constructs, where nutrient supply from the surrounding
culture medium is most abundant, whereas cells in the interior receive
less nutrients and produce less matrix, with poorer functional
properties. In this presentation, we show that dynamic mechanical
loading can enhance
solute transport by up to an order of magnitude, and this enhancement
can be considerably accelerated by placing channels in the constructs.
