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Alternative sterilization treatments, such as supercritical carbon dioxide (SCCO<jats:sub>2<\/jats:sub>), are gaining popularity due to advantages such as minimal exposure to denaturants, the lack of toxic residues, superior tissue penetration, and minor impacts on mechanical properties including strength and stiffness. The impact of SCCO<jats:sub>2<\/jats:sub> on the fracture toughness of bone tissue, however, remains unknown. Here, we evaluate crack initiation and growth toughness after 2, 6, and 24\u2009h SCCO<jats:sub>2<\/jats:sub>\u2010treatment using Novakill\u2122 and ethanol as additives on ~11 samples per group obtained from a pair of femur diaphyses of a canine. All mechanical testing was performed at ambient air after 24\u2009h soaking in Hanks' balanced salt solution (HBSS). Results show no statistically significant difference in the failure characteristics of the Novakill\u2122\u2010treated groups whereas crack growth toughness after 6 and 24\u2009h of treatment with ethanol significantly increases by 37% (<jats:italic>p<\/jats:italic>\u2009=\u2009.010) and 34% (<jats:italic>p<\/jats:italic>\u2009=\u2009.038), respectively, compared to an untreated control group. In contrast, standard 25\u2009kGy gamma irradiation causes significantly reduced crack growth resistance by 40% (<jats:italic>p<\/jats:italic>\u2009=\u2009.007) compared to untreated bone. FTIR vibrational spectroscopy, conducted after testing, reveals a consistent trend of statistically significant differences (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) with fracture toughness. These trends align with variations in the ratios of enzymatic mature to immature crosslinks in the collagen structure, suggesting a potential association with fracture toughness. Additional Raman spectroscopy after testing shows a similar trend with statistically significant differences (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.005), which further supports that collagen structural changes occur in the SCF\u2010treated groups with ethanol after 6 and 24\u2009h. Our work reveals the benefits of SCCO<jats:sub>2<\/jats:sub> sterilization compared to gamma irradiation.<\/jats:p>","DOI":"10.1002\/jbm.b.35356","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T02:40:05Z","timestamp":1703126405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of gamma irradiation and supercritical carbon dioxide sterilization with <scp>Novakill\u2122<\/scp> or ethanol on the fracture toughness of cortical bone"],"prefix":"10.1002","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-3690","authenticated-orcid":false,"given":"Mihee","family":"Shin","sequence":"first","affiliation":[{"name":"School of Mechanical and Manufacturing Engineering, University of New South Wales (UNSW Sydney)  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew H.","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Surgical and Orthopedic Research Laboratories Prince of Wales Clinical School, University of New South Wales (UNSW Sydney)  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vedran","family":"Lovric","sequence":"additional","affiliation":[{"name":"Surgical and Orthopedic Research Laboratories Prince of Wales Clinical School, University of New South Wales (UNSW Sydney)  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5023-6148","authenticated-orcid":false,"given":"William R.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Surgical and Orthopedic Research Laboratories Prince of Wales Clinical School, University of New South Wales (UNSW Sydney)  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3098-1420","authenticated-orcid":false,"given":"Penny J.","family":"Martens","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Engineering, University of New South Wales (UNSW Sydney)  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9695-1921","authenticated-orcid":false,"given":"Jamie J.","family":"Kruzic","sequence":"additional","affiliation":[{"name":"School of Mechanical and Manufacturing Engineering, University of New South Wales (UNSW Sydney)  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2420-3879","authenticated-orcid":false,"given":"Bernd","family":"Gludovatz","sequence":"additional","affiliation":[{"name":"School of Mechanical and Manufacturing Engineering, University of New South Wales (UNSW Sydney)  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-200006000-00026"},{"key":"e_1_2_12_3_1","volume-title":"Sterilization of Medical Devices\u2010Microbiological Methods. 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