Composition/Functional Elasticity of Engineered Tissues

DESCRIPTION: (provided by applicant) Tissue engineering is an emerging field in
reconstructive surgery of dental and other craniofacial features consisting of
skin, bone, or cartilage. In one common approach to tissue repair, cells
capable of proliferating and synthesizing extracellular matrix (ECM) proteins
are seeded on three-dimensional biodegradable polymer scaffolds. The scaffolds
provide mechanical stability and geometric form to the construct until the
cellular and biochemical components develop into competent tissue. In the
design of engineered tissues, balancing the processes of biomaterial
degeneration with tissue synthesis is critical in the initial phases of healing
and long-term success. The combination of these two processes provides the mass
and volumetric balance of materials that are intended to maintain the
biological and mechanical health of repairing tissue. These complementary,
time-dependent processes are often defined only empirically due to the lack of
established parametric relationships. It is hypothesized that mathematical
models can be developed to describe the dynamic mass state of concomitant
scaffold degeneration and tissue synthesis. The model can be experimentally
validated to confirm constituent quality and predict functional elastic
parameters of the engineered tissue composite. The model will also provide
design criteria and performance specifications to optimize the development of
engineered tissues within the in vivo biologic and mechanical environment. It
is intended that the general relationships defined in this project can be
modified for all engineered tissue types. In the following proposal, two
dynamic mass models (polyrmer and ECM mass) will be developed to define a
construct elastic model of cartilage. These models will be directly validated
through cell-culture and mechanical experiments. Poly-glycolic acid (PGA)
scaffolds will be seeded with chondrocytes and cultured in vitro for up to 10
weeks. The polymer mass, ECM component masses (collagen and glycosaminoglycan),
and elastic modulus of the constructs will be quantified at regular intervals.
The results will be used to predict the time-dependent performance of
cell-polymer constructs, and to gain insight into the mechanisms of scaffold
degradation and ECM synthesis.