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The clinical standard of repairing bone defects using autografts or allografts has many drawbacks. A bioactive ceramic scaffold, strontium\u2010hardystonite\u2010gahnite or \u201cSr\u2010HT\u2010Gahnite\u201d (a multi\u2010component, calcium silicate\u2010based ceramic) is developed, which when 3D\u2010printed combines high strength with outstanding bone regeneration ability. In this study, the performance of purely synthetic, 3D\u2010printed Sr\u2010HT\u2010Gahnite scaffolds is assessed in repairing large and load\u2010bearing bone defects. The scaffolds are implanted into critical\u2010sized segmental defects in sheep tibia for 3 and 12 months, with bone autografts used for comparison. The scaffolds induce substantial bone formation and defect bridging after 12 months, as indicated by X\u2010ray, micro\u2010computed tomography, and histological and biomechanical analyses. Detailed analysis of the bone\u2010scaffold interface using focused ion beam scanning electron microscopy and multiphoton microscopy shows scaffold degradation and maturation of the newly formed bone. In silico modeling of strain energy distribution in the scaffolds reveal the importance of surgical fixation and mechanical loading on long\u2010term bone regeneration. The clinical application of 3D\u2010printed Sr\u2010HT\u2010Gahnite scaffolds as a synthetic bone substitute can potentially improve the repair of challenging bone defects and overcome the limitations of bone graft transplantation.<\/jats:p>","DOI":"10.1002\/adhm.201801298","type":"journal-article","created":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T04:03:16Z","timestamp":1550462596000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["A Novel Bone Substitute with High Bioactivity, Strength, and Porosity for Repairing Large and Load\u2010Bearing Bone Defects"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3584-6765","authenticated-orcid":false,"given":"Jiao Jiao","family":"Li","sequence":"first","affiliation":[{"name":"Biomaterials and Tissue Engineering Research Unit School of Aerospace, Mechanical and Mechatronic Engineering University of Sydney  Sydney NSW 2006 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