{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:40:00Z","timestamp":1792795200828,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Nonunion following fracture treatment remains a significant clinical challenge, adversely affecting the patient\u2019s quality of life and imposing a substantial economic burden. The emergence of bone morphogenetic protein 2 (BMP-2) for bone regeneration represents a promising avenue, albeit limited by side effects such as inflammatory reactions primarily due to suboptimal drug delivery systems. This study focuses on NOVOSIS putty (NP), a novel biomaterial designed for the sustained release of BMP-2, aiming to mitigate these limitations and enhance bone healing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This research aimed to evaluate the effectiveness of NP, a hydroxyapatite granules\/\u03b2-tricalcium phosphate hydrogel composite (HA\/\u03b2-TCP\/hydrogel), as a BMP-2 carrier for promoting bone regeneration in a new rat nonunion model of long bone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using Sprague Dawley rats, a 2-mm silicone disk was interposed at the femoral fracture site, and intramedullary fixation with K-wire was performed to create a nonunion with a 2-mm bone defect. After 3\u00a0weeks, internal fixation with a plate, removal of the silicon disk, and refreshing the nonunion site were performed by implanting three different materials into the nonunion sites: allogenic iliac bone (IB), collagen sponge (CS) containing 10\u00a0\u03bcg of BMP-2, or NP containing 10\u00a0\u03bcg of BMP-2. Bone healing was evaluated weekly using micro-computed tomography (CT); <jats:italic>ex vivo<\/jats:italic> micro-Ct and histological evaluation were conducted at 6\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At 6\u00a0weeks, NP demonstrated a significantly higher bone union rate (76.5%) compared with the CS group (35.3%, <jats:italic>p<\/jats:italic> = 0.037), and the IB group (6.3%, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001). Bone mineral density (BMD) and bone volume\/tissue volume (BV\/TV) were also significantly higher in the NP group compared with the CS group (BMD, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001; BV\/TV, <jats:italic>p<\/jats:italic> = 0.031). Histological analysis showed the fracture gap in the NP group was filled with more trabecular bone and less fibrous tissue compared with the CS group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The study confirms NP is a highly effective BMP-2 carrier, significantly improving bone union rates and new bone formation in nonunion fractures. The sustained release of BMP-2 from the hydrogel component reduced inflammatory responses and enhanced bone regeneration. NP can be a promising alternative to collagen-based BMP-2 delivery systems.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbioe.2024.1461260","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T13:58:36Z","timestamp":1728309516000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["rhBMP-2-loaded hydroxyapatite\/beta-tricalcium phosphate microsphere\/hydrogel composite promotes bone regeneration in a novel rat femoral nonunion model"],"prefix":"10.3389","volume":"12","author":[{"given":"Takayuki","family":"Kitahara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Tateiwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Hirai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Ikuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Furuichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Bun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Ukon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Kanie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Furuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahito","family":"Fujimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kaito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1097\/00003086-199608000-00037","article-title":"Complications of iliac crest bone graft harvesting","volume":"329","author":"Arrington","year":"1996","journal-title":"Clin. 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