{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:36:08Z","timestamp":1777887368053,"version":"3.51.4"},"reference-count":35,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Metabolic Engineering"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.ymben.2025.07.004","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T15:15:32Z","timestamp":1752592532000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Biomass accumulation in chondrocyte metabolic modelling: Incorporating extracellular matrix proxies to predict tissue engineering outcomes"],"prefix":"10.1016","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6644-8209","authenticated-orcid":false,"given":"Roberto","family":"Tarantino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Halie Mei","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-6973","authenticated-orcid":false,"given":"Stephen D.","family":"Waldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymben.2025.07.004_bib1","series-title":"A Guide to 13C Metabolic Flux Analysis for the Cancer Biologist","author":"Antoniewicz","year":"2018"},{"key":"10.1016\/j.ymben.2025.07.004_bib2","series-title":"Cross-Talk of Inflammation and Chondrocyte Intracellular Metabolism in Osteoarthritis","author":"Arra","year":"2023"},{"issue":"2","key":"10.1016\/j.ymben.2025.07.004_bib3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S1063-4584(05)80044-5","article-title":"Characterization of proteoglycan accumulation during formation of cartilagenous tissue in vitro","volume":"3","author":"Boyle","year":"1995","journal-title":"Osteoarthr. Cartil."},{"issue":"4","key":"10.1016\/j.ymben.2025.07.004_bib4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1089\/ten.tec.2017.0018","article-title":"A modified hydroxyproline assay based on hydrochloric acid in Ehrlich's solution accurately measures tissue collagen content","volume":"23","author":"Cissell","year":"2017","journal-title":"Tissue Eng. C Methods"},{"issue":"2","key":"10.1016\/j.ymben.2025.07.004_bib5","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ymben.2011.12.005","article-title":"Selection of tracers for 13C-Metabolic flux analysis using Elementary Metabolite Units (EMU) basis vector methodology","volume":"14","author":"Crown","year":"2012","journal-title":"Metab. Eng."},{"key":"10.1016\/j.ymben.2025.07.004_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.biosystems.2023.105004","article-title":"Control analysis of collagen synthesis by glycine, proline and lysine in bovine chondrocytes in vitro \u2013 its relevance for medicine and nutrition","volume":"232","author":"de Paz-Lugo","year":"2023","journal-title":"Biosystems"},{"issue":"Jun","key":"10.1016\/j.ymben.2025.07.004_bib7","article-title":"13C-metabolic flux analysis of Saccharomyces cerevisiae in complex media","volume":"20","author":"Fujiwara","year":"2025","journal-title":"Metab Eng Commun"},{"issue":"4","key":"10.1016\/j.ymben.2025.07.004_bib8","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00424-007-0310-7","article-title":"Oxygen and reactive oxygen species in articular cartilage: modulators of ionic homeostasis","volume":"455","author":"Gibson","year":"2007","journal-title":"Pfl\u00fcgers Archiv"},{"issue":"3\u20134","key":"10.1016\/j.ymben.2025.07.004_bib9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3109\/03008209009152154","article-title":"An improved method for determining Proteoglycans synthesized by chondrocytes in culture","volume":"24","author":"Goldberg","year":"1990","journal-title":"Connect. Tissue Res."},{"key":"10.1016\/j.ymben.2025.07.004_bib10","doi-asserted-by":"crossref","DOI":"10.1002\/term.211","article-title":"Effects of mechanical loading on collagen propeptides processing in cartilage repair","author":"Hardmeier","year":"2009","journal-title":"J. Tissue Eng. Regen. Med."},{"issue":"4","key":"10.1016\/j.ymben.2025.07.004_bib11","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00726-021-03056-x","article-title":"Hydroxyproline in animal metabolism, nutrition, and cell signaling","volume":"54","author":"Hu","year":"2022","journal-title":"Amino Acids"},{"key":"10.1016\/j.ymben.2025.07.004_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiomed.2023.107039","article-title":"Modeling of glycosaminoglycan biosynthesis in intervertebral disc cells","volume":"162","author":"Huang","year":"2023","journal-title":"Comput. Biol. Med."},{"key":"10.1016\/j.ymben.2025.07.004_bib13","unstructured":"Jazmin, L.J., Beckers, V., Young, J.D., 2014. User Manual for INC."},{"issue":"5","key":"10.1016\/j.ymben.2025.07.004_bib14","doi-asserted-by":"crossref","DOI":"10.3390\/metabo12050469","article-title":"Increased ammonium toxicity in response to exogenous glutamine in metastatic breast cancer cells","volume":"12","author":"Kiesel","year":"2022","journal-title":"Metabolites"},{"issue":"1","key":"10.1016\/j.ymben.2025.07.004_bib15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0014-4827(71)90584-2","article-title":"Kinetics of matrix synthesis in cartilage cell cultures","volume":"68","author":"Lavietes","year":"1971","journal-title":"Exp. Cell Res."},{"issue":"3","key":"10.1016\/j.ymben.2025.07.004_bib16","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/bit.20490","article-title":"Tissue engineering of human cartilage in bioreactors using single and composite cell-seeded scaffolds","volume":"91","author":"Mahmoudifar","year":"2005","journal-title":"Biotechnol. Bioeng."},{"issue":"2","key":"10.1016\/j.ymben.2025.07.004_bib17","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.berh.2008.02.001","article-title":"Cartilage in normal and osteoarthritis conditions","volume":"22","author":"Martel-Pelletier","year":"2008","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"issue":"8","key":"10.1016\/j.ymben.2025.07.004_bib18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11306-023-02031-9","article-title":"Monitoring and modelling the glutamine metabolic pathway: a review and future perspectives","volume":"19","author":"Mirveis","year":"2023","journal-title":"Metabolomics"},{"key":"10.1016\/j.ymben.2025.07.004_bib19","series-title":"Isotope-Assisted Metabolic Flux Analysis: a Powerful Technique to Gain New Insights into the Human Metabolome in Health and Disease","author":"Moiz","year":"2022"},{"key":"10.1016\/j.ymben.2025.07.004_bib20","series-title":"Fitting Models to Biological Data Using Linear and Nonlinear Regression: a Practical Guide to Curve Fitting","article-title":"Comparing models using the extra sum-of-squares F test introducing the extra sum-of-squares F test","author":"Motulsky","year":"2004"},{"key":"10.1016\/j.ymben.2025.07.004_bib21","series-title":"A Narrative Review,\u201d","article-title":"\u201cThe role of targeting glucose metabolism in chondrocytes in the pathogenesis and therapeutic mechanisms of osteoarthritis","author":"Pi","year":"2024"},{"issue":"2","key":"10.1016\/j.ymben.2025.07.004_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2020.100855","article-title":"Dynamic 13C flux analysis captures the reorganization of adipocyte glucose metabolism in response to insulin","volume":"23","author":"Quek","year":"2020","journal-title":"iScience"},{"key":"10.1016\/j.ymben.2025.07.004_bib23","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ymben.2021.12.009","article-title":"Inca 2.0: a tool for integrated, dynamic modeling of NMR- and MS-based isotopomer measurements and rigorous metabolic flux analysis","volume":"69","author":"Rahim","year":"2022","journal-title":"Metab. Eng."},{"issue":"1","key":"10.1016\/j.ymben.2025.07.004_bib24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10237-018-1068-x","article-title":"Physiological dynamic compression regulates central energy metabolism in primary human chondrocytes","volume":"18","author":"Salinas","year":"2019","journal-title":"Biomech. Model. Mechanobiol."},{"issue":"8","key":"10.1016\/j.ymben.2025.07.004_bib25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0023119","article-title":"Strategies for enhancing the accumulation and retention of extracellular matrix in tissue-engineered cartilage cultured in bioreactors","volume":"6","author":"Shahin","year":"2011","journal-title":"PLoS One"},{"issue":"8","key":"10.1016\/j.ymben.2025.07.004_bib26","doi-asserted-by":"crossref","first-page":"3409","DOI":"10.1016\/j.actbio.2014.04.013","article-title":"Semi-interpenetrating networks of hyaluronic acid in degradable PEG hydrogels for cartilage tissue engineering","volume":"10","author":"Skaalure","year":"2014","journal-title":"Acta Biomater."},{"issue":"6","key":"10.1016\/j.ymben.2025.07.004_bib27","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/1941738109350438","article-title":"The basic science of articular cartilage: structure, composition, and function","volume":"1","author":"Sophia Fox","year":"2009","journal-title":"Sport Health"},{"issue":"5","key":"10.1016\/j.ymben.2025.07.004_bib28","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.devcel.2020.05.001","article-title":"Glutamine metabolism controls Chondrocyte identity and function","volume":"53","author":"Stegen","year":"2020","journal-title":"Dev. Cell"},{"issue":"10","key":"10.1016\/j.ymben.2025.07.004_bib29","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1002\/bit.27888","article-title":"Effect of nutrient metabolism on cartilaginous tissue formation","volume":"118","author":"Tarantino","year":"2021","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2025.07.004_bib30","doi-asserted-by":"crossref","DOI":"10.1089\/ten.tea.2023.0321","article-title":"13C metabolic flux analysis in chondrocytes reveals a novel switch in metabolic phenotype","author":"Tarantino","year":"2024","journal-title":"Tissue Eng Part A"},{"issue":"7","key":"10.1016\/j.ymben.2025.07.004_bib31","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.joca.2024.03.119","article-title":"Elevated nutrient availability enhances chondrocyte metabolism and biosynthesis in tissue-engineered cartilage","volume":"32","author":"Tarantino","year":"2024","journal-title":"Osteoarthr. Cartil."},{"issue":"3\u20134","key":"10.1016\/j.ymben.2025.07.004_bib32","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1089\/ten.tea.2014.0103","article-title":"Collagen type XII and versican are present in the early stages of cartilage tissue formation by both redifferentating passaged and primary chondrocytes","volume":"21","author":"Taylor","year":"2015","journal-title":"Tissue Eng Part A"},{"issue":"1","key":"10.1016\/j.ymben.2025.07.004_bib33","doi-asserted-by":"crossref","DOI":"10.1242\/bio.058895","article-title":"Effects of mechanical stimulation on metabolomic profiles of SW1353 chondrocytes: shear and compression","volume":"11","author":"Welhaven","year":"2022","journal-title":"Biol Open"},{"issue":"1","key":"10.1016\/j.ymben.2025.07.004_bib34","doi-asserted-by":"crossref","DOI":"10.1002\/0471140864.psa03fs13","article-title":"Protein precipitation using ammonium sulfate","volume":"13","author":"Wingfield","year":"1998","journal-title":"Curr Protoc Protein Sci"},{"key":"10.1016\/j.ymben.2025.07.004_bib35","series-title":"Proteoglycan Protocols","first-page":"3","article-title":"Isolation of proteoglycans from cell cultures and tissues","author":"Yanagishita","year":"2001"}],"container-title":["Metabolic Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096717625001089?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096717625001089?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:10:02Z","timestamp":1777608602000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1096717625001089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":35,"alternative-id":["S1096717625001089"],"URL":"https:\/\/doi.org\/10.1016\/j.ymben.2025.07.004","relation":{},"ISSN":["1096-7176"],"issn-type":[{"value":"1096-7176","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Biomass accumulation in chondrocyte metabolic modelling: Incorporating extracellular matrix proxies to predict tissue engineering outcomes","name":"articletitle","label":"Article Title"},{"value":"Metabolic Engineering","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymben.2025.07.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 International Metabolic Engineering Society. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}