{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:06:09Z","timestamp":1779426369342,"version":"3.53.1"},"reference-count":139,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interbody fusion cages are widely used to restore spinal stability, yet conventional designs often exhibit mechanical mismatch and limited biological integration. Functionally graded spinal cages incorporate spatial variations in composition and structure to better align mechanical properties with the surrounding bone environment. Although these designs have been extensively studied from an engineering perspective, their biological implications remain less clearly defined. This review examines how graded material composition, surface characteristics, porosity, and lattice architecture are associated with cellular and molecular responses relevant to bone regeneration. Reported biological responses include protein adsorption, immune modulation, angiogenesis, and osteogenic differentiation. Evidence from orthopaedic implants and tissue engineering systems suggests that such design features may influence mechanobiological pathways; however, direct experimental validation in spinal applications remains limited. Previous reviews primarily focus on material properties or mechanical performance of functionally graded spinal cages. This review presents a structured design-to-biology perspective linking graded implant features with biological responses relevant to spinal fusion. By integrating findings across biomaterials, mechanobiology, and implant design, this review presents a structured design-to-biology perspective and highlights current evidence, translational limitations, and key knowledge gaps in the field. Functionally graded spinal cages represent a promising but still evolving strategy, and further spine-specific mechanobiological and clinical studies are required to establish their impact on fusion outcomes.<\/jats:p>","DOI":"10.3390\/ijms27104531","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:35:43Z","timestamp":1779176143000},"page":"4531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Structures and Biology: Cellular and Molecular Interactions with Functionally Graded Spinal Cage Designs"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5779-6159","authenticated-orcid":false,"given":"Yuen Ho","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, School of Engineering, RMIT University, Melbourne 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8871-358X","authenticated-orcid":false,"given":"Amy Libing","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Engineering, RMIT University, Melbourne 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4919-5078","authenticated-orcid":false,"given":"Jessica","family":"Gaff","sequence":"additional","affiliation":[{"name":"Neurospine Institute, Murdoch, Perth 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-1660","authenticated-orcid":false,"given":"Gianluca","family":"Vadala","sequence":"additional","affiliation":[{"name":"Laboratory of Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Tavakoli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Engineering, RMIT University, Melbourne 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tavakoli, J., Diwan, A.D., and Tipper, J.L. 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