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Currently, arthroscopic techniques and autologous transplantation are the most used clinical procedures. However, rather than restoring cartilage integrity, these methods only postpone further cartilage deterioration. Therefore, tissue engineering strategies aimed at selecting scaffolds that remarkably support the chondrogenic differentiation of human mesenchymal stem cells (hMSCs) could represent a promising solution, but they are still challenging for researchers. In this study, the influence of two different genipin (<jats:sc>Gp<\/jats:sc>) crosslinking routes on collagen (<jats:sc>Coll<\/jats:sc>)\u2010based scaffolds in terms of hMSCs chondrogenic differentiation and biomechanical performances was investigated. Three\u2010dimensional (3D) porous <jats:sc>Coll<\/jats:sc> scaffolds were fabricated by freeze\u2010drying techniques and were crosslinked with <jats:sc>Gp<\/jats:sc> following a \u201c<jats:italic>two\u2010step<\/jats:italic>\u201d and an in \u201c<jats:italic>bulk<\/jats:italic>\u201d procedure, in order to increase the physico\u2010mechanical stability of the structure. Chondrogenic differentiation efficacy of hMSCs and biomechanical behavior under compression forces through unconfined stress\u2013strain tests were assessed. <jats:sc>Coll<\/jats:sc>\/<jats:sc>Gp<\/jats:sc> scaffolds revealed an isotropic and highly homogeneous pore distribution along with an increase in the stiffness, also supported by the increase in the <jats:sc>Coll<\/jats:sc> denaturation temperature (<jats:italic>T<\/jats:italic><jats:sub><jats:italic>d<\/jats:italic><\/jats:sub>\u00a0=\u00a057\u201363\u00b0C) and a significant amount of <jats:sc>Coll<\/jats:sc> and GAG deposition during the 3\u00a0weeks of chondrogenic culture. In particular, the presence of <jats:sc>Gp<\/jats:sc> in \u201c<jats:italic>bulk<\/jats:italic>\u201d led to a more uniform and homogenous chondral\u2010like matrix deposition by hMSCs if compared to the results obtained from the <jats:sc>Gp<\/jats:sc> \u201c<jats:italic>two\u2010step<\/jats:italic>\u201d functionalization procedure.<\/jats:p>","DOI":"10.1002\/jbm.a.37379","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T13:17:49Z","timestamp":1646831869000},"page":"1372-1385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genipin\u2010crosslinked collagen scaffolds inducing chondrogenesis: a mechanical and biological characterization"],"prefix":"10.1002","volume":"110","author":[{"given":"Stefania","family":"Scialla","sequence":"first","affiliation":[{"name":"Department of Engineering for Innovation University of Salento  Lecce Italy"},{"name":"Institute of Polymers, 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