Time and dose-dependent effects of chondroitinase ABC on growth of engineered cartilage.
Tissue engineering techniques have been effective in developing cartilage-like tissues in vitro. However, many scaffold-based approaches to cultivating engineered cartilage have been limited by low collagen production, an impediment for attaining native functional load-bearing tensile mechanical properties. Enzymatic digestion of glycosaminoglycans (GAG) with chondroitinase ABC (chABC) temporarily suppresses the construct's GAG content and compressive modulus and increases collagen content. Based on the promising results of these early studies, the aim of this study was to further promote collagen deposition through more frequent chABC treatments. Weekly dosing of chABC at a concentration of 0.15 U/mL resulted in a significant cell death, which impacted the ability of the engineered cartilage to fully recover GAG and compressive mechanical properties. In light of these findings, the influence of lower chABC dosage on engineered tissue (0.004 and 0.015 U/mL) over a longer duration (one week) was investigated. Treatment with 0.004 U/mL reduced cell death, decreased the recovery time needed to achieve native compressive mechanical properties and GAG content, and resulted in a collagen content that was 65 % greater than the control. In conclusion, the results of this study demonstrate that longer chABC treatment (one week) at low concentrations can be used to improve collagen content in developing engineered cartilage more expediently than standard chABC treatments of higher chABC doses administered over brief durations.
Columbia University, Biomedical Engineering Department, 351 Engineering Terrace, New York, NY 10027, USA.cth6@columbia.edu.
G D
GD
O'Connell
R J
RJ
Nims
J
J
Green
A D
AD
Cigan
G A
GA
Ateshian
C T
CT
Hung
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D019765:Chondroitin ABC Lyase / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006025:Glycosaminoglycans / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods
D006025:Glycosaminoglycans; D003094:Collagen; D019765:Chondroitin ABC Lyase