{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:42:41Z","timestamp":1792172561035,"version":"4.4.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"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>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>During the healing process, the functional gradient attachment of the rotator cuff (RC) tendon-bone interface fails to regenerate, which severely impedes load transfer and stress dissipation, thereby increasing the risk of retears. As a result, the treatment of rotator cuff tears remains a significant clinical challenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, a dual-crosslinked hyaluronic acid\/polyethylene glycol (HA\/PEG) hydrogel scaffold was synthesized using hyaluronic acid and polyethylene glycol as base materials. Manganese-doped mesoporous silica nanoparticles (Mn-MSN) were incorporated into the hydrogel system to fabricate a manganese-based mesoporous silica nanoparticle-loaded dual-crosslinked hydrogel (Mn-MSN@Gel). The physicochemical properties of Mn-MSN@Gel, including porosity, elemental distribution, mechanical properties, biodegradability, and biocompatibility, were systematically characterized. The ion release profiles of Si\n                      <jats:sup>4+<\/jats:sup>\n                      and Mn\n                      <jats:sup>4+<\/jats:sup>\n                      were evaluated to assess sustained delivery. Rheological properties and self-healing capabilities were examined to determine injectability and in vivo stability. In vitro, the effects of Mn-MSN@Gel on cell migration, proliferation, and differentiation were assessed using rat bone marrow mesenchymal stem cells (rat-BMSCs) and tendon-derived stem cells (rat-TDSCs). The expression of osteogenic, tenogenic, oxidative stress-related, and inflammatory cytokine genes was analyzed. In vivo, a rat rotator cuff repair model was established to evaluate the biomechanical properties and tissue regeneration at the tendon-bone interface (TBI) following Mn-MSN@Gel injection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Characterization demonstrated that Mn-MSN@Gel possesses a porous three-dimensional structure with uniform distribution of silicon, oxygen, and manganese elements, enabling sustained and slow release of Si\n                      <jats:sup>4+<\/jats:sup>\n                      and Mn\n                      <jats:sup>4+<\/jats:sup>\n                      ions. Additionally, the composite material exhibited excellent mechanical properties, biodegradability, and biocompatibility, while promoting cell migration\/proliferation and accelerating regeneration of the tendon-bone interface. Mn-MSN@Gel enhanced the expression of osteogenic differentiation genes (Runx2, Alp, Sox9) in rat-BMSCs, upregulated tenogenic differentiation markers (Scx, Tnmd, Col3a1), and downregulated Mmp3 expression in rat-TDSCs. Furthermore, Mn-MSN@Gel modulated genes related to oxidative stress (Nrf2, Gpx4, Sod2) and inflammatory cytokines (IL-6, IL-10, Tnf-\u03b1), exhibiting anti-inflammatory effects and alleviating oxidative stress damage. In the rat rotator cuff repair model, Mn-MSN@Gel injection significantly improved postoperative biomechanical properties and promoted tissue regeneration at the TBI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The self-healing and injectable properties of Mn-MSN@Gel ensure precise delivery and stable integration in vivo. By combining mechanical support with sustained release of bioactive ions, Mn-MSN@Gel provides a comprehensive therapeutic strategy for regenerative repair of the tendon-bone interface. Its biocompatibility and bioactivity facilitate cell recruitment, migration, and lineage-specific differentiation, which are crucial for reconstructing the functional gradient structure of the TBI. The anti-inflammatory and antioxidant effects further contribute to a favorable healing microenvironment. Overall, these findings indicate that Mn-MSN@Gel is a foundational biomaterial with significant therapeutic potential for enhancing structural regeneration and functional recovery of the TBI following rotator cuff injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2025.1645970","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:17:42Z","timestamp":1755764262000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Enhanced rotator cuff tendon-bone interface regeneration with injectable manganese-based mesoporous silica nanoparticle-loaded dual crosslinked hydrogels"],"prefix":"10.3389","volume":"13","author":[{"given":"Zihang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyuan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haobo","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JinJin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riwang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huajun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.jare.2013.07.006","article-title":"Hydrogel: preparation, characterization, and applications: a review","volume":"6","author":"Ahmed","year":"2015","journal-title":"J. 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