Formation of tissue-engineered cartilage is greatly enhanced by mechanical stimulation. However, direct mechanical stimulation is not always a suitable method, and the utilization of mechanisms underlying mechanotransduction might allow for a highly effective and less aggressive alternate means of stimulation. In particular, the purinergic, adenosine 5-triphosphate (ATP)-mediated signaling pathway is strongly implicated in mechanotransduction within the articular cartilage. We investigated the effects of transient and continuous exogenous ATP supplementation on mechanical properties of cartilaginous constructs engineered using bovine chondrocytes and human mesenchymal stem cells (hMSCs) encapsulated in an agarose hydrogel. For both cell types, we have observed significant increases in equilibrium and dynamic compressive moduli after transient ATP treatment applied in the fourth week of cultivation. Continuous ATP treatment over 4 weeks of culture only slightly improved the mechanical properties of the constructs, without major changes in the total glycosaminoglycan (GAG) and collagen content. Structure-function analyses showed that transiently ATP-treated constructs, and in particular those based on hMSCs, had the highest level of correlation between compositional and mechanical properties. Transiently treated groups showed intense staining of the territorial matrix for GAGs and collagen type II. These results indicate that transient ATP treatment can improve functional mechanical properties of cartilaginous constructs based on chondrogenic cells and agarose hydrogels, possibly by improving the structural organization of the bulk phase and territorial extracellular matrix (ECM), that is, by increasing correlation slopes between the content of the ECM components (GAG, collagen) and mechanical properties of the construct.
Supplementation of Exogenous Adenosine 5-Triphosphate Enhances Mechanical Properties of 3D Cell-Agarose Constructs for Cartilage Tissue Engineering
Creators
Ivana Gadjanski - Columbia University
Supansa Yodmuang - Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA
Kara Spiller - Columbia University
Sarindr Bhumiratana - Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA
Gordana Vunjak-Novakovic - Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA
Publication Details
Tissue engineering. Part A, v 19(19-20), pp 2188-2200
Publisher
Mary Ann Liebert, Inc
Number of pages
13
Grant note
P41EB002520 / NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)
Royal Thai Graduate Fellowship
R01DE016525 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR)
DE016525; EB002520; EB011869 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
R01AR061988 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
ON174028; III41007 / Ministry of education and science of Republic of Serbia; Ministry of Education, Science & Technological Development, Serbia
Resource Type
Journal article
Language
English
Academic Unit
School of Biomedical Engineering, Science, and Health Systems
Web of Science ID
WOS:000323933400011
Scopus ID
2-s2.0-84883709758
Other Identifier
991019176794004721
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