TY - JOUR
T1 - Modeling the dynamic composition of engineered cartilage
AU - Wilson, Christopher G.
AU - Bonassar, Lawrence J.
AU - Kohles, Sean S.
N1 - Funding Information:
The authors recognize the technical contributions of Dr. Amit Roy, Dr. Jill Rulfs, Nicholas Genes, Nichole Mercier, Morgan Hott, Brett Downing, and Dr. George Pins. Funding for this project was provided by the Center for Tissue Engineering, University of Massachusetts Medical School, the Office for Academic Affairs, Worcester Polytechnic Institute, and Grant DE014288 from the National Institute for Dental and Craniofacial Research.
PY - 2002
Y1 - 2002
N2 - 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 (R2 = 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.
AB - 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 (R2 = 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.
KW - Biodegradable polymers
KW - Biosynthesis
KW - Cartilage
KW - Extracellular matrix
KW - Mathematical model
KW - Tissue engineering
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U2 - 10.1016/S0003-9861(02)00562-3
DO - 10.1016/S0003-9861(02)00562-3
M3 - Article
C2 - 12464278
AN - SCOPUS:0036910980
SN - 0003-9861
VL - 408
SP - 246
EP - 254
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -