Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 408, Issue 2, Pages 246-254Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0003-9861(02)00562-3
Keywords
cartilage; mathematical model; tissue engineering; extracellular matrix; biosynthesis; biodegradable polymers
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Funding
- NIDCR NIH HHS [R03 DE014288, DE014288, R03 DE014288-01A1] Funding Source: Medline
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Mathematical models to describe extracellular matrix (ECM) deposition and scaffold degradation in cell-polymer constructs for the design of engineered cartilage were developed and validated. The ECM deposition model characterized a product-inhibition mechanism in the concentration of cartilage molecules, collagen and glycosaminoglycans (GAG). The scaffold degradation model used first-order kinetics to describe hydrolysis (not limited by diffusion) of biodegradable polyesters, polyglycolic acid and polylactic acid. Each model was fit to published accumulation and degradation data. As experimental validation, cell-polymer constructs (n=24) and unseeded scaffolds (n=24) were cultured in vitro. Biochemical assays for ECM content and measurements of scaffold mass were performed at 1, 2, 4, 6, 8, or 10 weeks (n=8 per time point). The models demonstrated a strong fit with published data and experimental results (R-2=0.75 to 0.99) and predicted the temporal total construct mass with reasonable accuracy (30% RMS error). This approach can elucidate mechanisms governing accumulation/degradation and may be coupled with structure-function relationships to describe time-dependent changes in construct elastic properties. (C) 2002 Elsevier Science (USA). All rights reserved.
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