{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:47:16Z","timestamp":1788382036772,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education","doi-asserted-by":"publisher","award":["FRGS\/1\/2022\/SKK10\/UKM\/01\/2"],"award-info":[{"award-number":["FRGS\/1\/2022\/SKK10\/UKM\/01\/2"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oral administration of tocotrienol has poor systemic distribution due to poor selectivity by the \u03b1-tocopherol transfer protein at the liver. Local injection of tocotrienols with appropriate drug delivery systems is significant to ensure that the drug is delivered directly to the site of injury or fracture. This paper presents a tocotrienol-loaded gelatin hydrogel crosslinked with genipin for bone regeneration. This innovative method improves the incorporation and sustained delivery of tocotrienol while overcoming its incompatibility with hydrophilic biomaterials. It establishes a novel platform for targeted therapeutic applications in bone treatment. The cytotoxicity and physicochemical properties of tocotrienol were examined using the genipin-crosslinked gelatin hydrogel. A 10% tocotrienol nanoemulsion (TTE) was prepared using a sonicator and characterized with a zeta sizer and FTIR. A dose\u2013response analysis was conducted to determine the appropriate tocotrienol concentration for hydrogel integration with gelatin (7% or 10% w\/v) and crosslinked with genipin (0.1% or 0.3% w\/v). The dose\u2013response study\u2019s tocotrienol nanoemulsion was added to gelatin before polymerization. With 141.9 nm particles and 0.150 PDI, the nanoemulsion was homogeneous and stable. The 1% tocotrienol nanoemulsion was chosen due to its viability. Formulations 1% TTE_0.1% GNP_7% GEL and 1%TTE_0.3% GNP_7% GEL had superior physicochemical properties compared to other groups. The 1% TTE_0.3% GNP_7% GEL had outstanding hydrophilicity, low weight loss, and a suitable swelling ratio for bone application. SEM scans of the surface and cross-section showed that 1% TTE_0. 3% GNP_7% GEL had interconnected pores with an optimal average pore size of 292 \u00b1 37 \u03bcm. Adding tocotrienol to the gelatin hydrogel matrix did not affect FTIR, XRD, or EDX. In vitro cytotoxicity studies indicated &gt;90% cell viability of hFOB 1.19 cells cultured on 1% TTE_0.1% GNP_7% GEL and 1% TTE_0.3% GNP_7% GEL (105 \u00b1 4.36% and 95.36 \u00b1 9.78%). Combining tocotrienol with a genipin-crosslinked gelatin hydrogel demonstrated superior physicochemical properties and no in vitro toxicity.<\/jats:p>","DOI":"10.3390\/ijms27041659","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T08:15:54Z","timestamp":1770624954000},"page":"1659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tocotrienol-Incorporated Gelatin Hydrogel Crosslinked with Genipin for Future Bone Tissue Engineering Applications: Physiochemical Characterization and Biocompatibility"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7069-5045","authenticated-orcid":false,"given":"Alhareth Abdulraheem","family":"Al-Ajalein","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2486-9486","authenticated-orcid":false,"given":"Nurul \u2018Izzah","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6449-639X","authenticated-orcid":false,"given":"Mh Busra","family":"Fauzi","sequence":"additional","affiliation":[{"name":"Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia"},{"name":"Advance Bioactive Materials-Cells (Adv-BioMaC) UKM Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2480-0224","authenticated-orcid":false,"given":"Norazlina","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1900020","DOI":"10.1002\/mabi.201900020","article-title":"Precisely Controlled Delivery of Abaloparatide through Injectable Hydrogel to Promote Bone Regeneration","volume":"19","author":"Ning","year":"2019","journal-title":"Macromol. 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