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Current treatment modalities have several limitations and drawbacks, with limited capacity of restoration; however, tissue engineering shows promise in improving the clinical outcomes of osteochondral defects. In this study, a novel gradient scaffold has been fabricated, implementing a gradient structure in the design to mimic the anatomical, biological and physicochemical properties of bone and cartilage as closely as possible. Compared with the commonly studied multi-layer scaffolds, the gradient scaffold has the potential to induce a smooth transition between cartilage and bone and avoid any instability at the interface, mimicking the natural structure of the osteochondral tissue. The scaffold comprises a collagen matrix with a gradient distribution of low-crystalline hydroxyapatite particles. Physicochemical analyses confirmed phase and chemical compositions of the gradient scaffold and the distribution of the mineral phase along the gradient scaffold. Mechanical tests confirmed the gradient of stiffness throughout the scaffold, according to its mineral content. The gradient scaffold exhibited good biological performances both in vitro and in vivo. Biological evaluation of the scaffold, in combination with human bone-marrow\u2013derived mesenchymal stem cells, demonstrated that the gradient of composition and stiffness preferentially increased cell proliferation in different sub-regions of the scaffold, according to their high chondrogenic or osteogenic characteristics. The in vivo biocompatibility of the gradient scaffold was confirmed by its subcutaneous implantation in rats. The gradient scaffold was significantly colonised by host cells and minimal foreign body reaction was observed. The scaffold\u2019s favourable chemical, physical and biological properties demonstrated that it has good potential as an engineered osteochondral analogue for the regeneration of damaged tissue.<\/jats:p>","DOI":"10.1177\/2041731419896068","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T03:39:06Z","timestamp":1580441946000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":75,"title":["Biomimetic gradient scaffold of collagen\u2013hydroxyapatite for osteochondral regeneration"],"prefix":"10.1177","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6242-3784","authenticated-orcid":false,"given":"Cristian","family":"Parisi","sequence":"first","affiliation":[{"name":"Centre of Oral, Clinical & Translational Sciences, King\u2019s College London, London, UK"},{"name":"Department of Engineering for Innovation, University of Salento, Lecce, 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