{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:30:13Z","timestamp":1768469413849,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001460","name":"American Orthopaedic Foot and Ankle Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Non\u2010union remains a significant complication following ankle fusion procedures, underscoring the need for effective osteogenic adjuvants to improve boney healing and fusion outcomes. This study investigates the osteogenic potential of FK506 (Tacrolimus), both in vitro and in vivo, for enhanced ankle fusion. Known orthobiologics in the market, such as recombinant human platelet\u2010derived growth factor\u2010BB (rhPDGF\u2010BB), have been utilized to promote bone healing and were included in this study to assess their comparative and combinatory effects with FK506. Bovine marrow\u2010derived cells (MDCs) were cultured in 2D and 3D environments to assess temporal markers of osteogenesis: RUNX2 nuclear localization (early), Alizarin Red S staining (intermediate), and mineral deposition with micro\u2010computed tomography (late). A rabbit ankle fusion model (<jats:italic>t<\/jats:italic>\u2009=\u20094 weeks) was utilized to evaluate FK506's early in vivo efficacy. In 2D cultures, FK506 resulted in an increase, but rhPDGF\u2010BB and the combination of rhPDGF\u2010BB and FK506 yielded the highest mineral deposition. However, in 3D fibrin gel cultures, FK506 alone demonstrated the greatest bone volume and tissue mineralization. In vivo rabbit ankle studies revealed that while ankle joint fusion was not achieved, FK506\u2010treated animals consistently showed substantial bone formation anterior to the joint, indicating its potential for localized osteogenesis in the ankle environment. This study demonstrates FK506's osteogenic potential as a standalone or combinatorial therapy. These findings highlight the need for further optimization of FK506 delivery methods and fixation strategies to maximize its clinical utility in ankle fusion procedures.<\/jats:p><jats:p><jats:bold>Statement of Clinical Significance:<\/jats:bold> The investigation of FK506 represents a potential pharmacological strategy for enhancing fusion healing and improving patient outcomes.<\/jats:p>","DOI":"10.1002\/jor.70036","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T07:39:29Z","timestamp":1753083569000},"page":"1805-1812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Osteogenic Small Molecule FK506 for Enhanced Bone Formation in a Rabbit Ankle Fusion Model"],"prefix":"10.1002","volume":"43","author":[{"given":"Nicholas","family":"Huffman","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Emory University School of Medicine Atlanta Georgia 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