{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T07:08:03Z","timestamp":1784185683070,"version":"3.55.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.82302704"],"award-info":[{"award-number":["No.82302704"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Sports Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Rotator cuff repair (RCR) often fails because of poor tendon-bone interface (TBI) healing. Nerve growth factor (NGF) has been shown to regulate tenocyte function and promote regeneration, but it lacks sufficient systematic research, limiting its clinical translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To evaluate the therapeutic efficacy of NGF-encoding plasmid (pNGF) for TBI healing in a rat acute rotator cuff tear (RCT) model, delivered via nanosphere-hydrogel (NP-GEL) composites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design:<\/jats:title>\n                    <jats:p>Controlled laboratory study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We performed physicochemical characterization of pNGF-loaded NP-GEL (morphology, particle size\/zeta potential, and in vitro pNGF release) and assessed rat tenocyte responses (proliferation, migration, and protein expression) in vitro. For in vivo studies, 42 Sprague-Dawley rats were randomized into 3 groups after bilateral acute RCT model establishment: RCR alone (control group), RCR combined with local empty plasmid-loaded NP-GEL composites (pEmpty@NP\/GEL group), and RCR combined with local pNGF-loaded NP-GEL composites (pNGF@NP\/GEL group). Rats were euthanized at 4 and 8 weeks postoperatively (n = 7 rats per time point, 14 shoulders\/group). At 4 weeks, 8 shoulders\/group were allocated to biomechanical testing, and 6 shoulders\/group to histologic analysis. At 8 weeks, 8 shoulders\/group underwent pain threshold and gait analysis before biomechanical testing, while 6 shoulders\/group underwent micro-computed tomography imaging before histologic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In vitro, pNGF@NP\/GEL exhibited pH-responsive sustained release (88% at pH 5, 76% at pH 7 over 28 days), and pNGF maximized primary tenocyte proliferation\/migration (peak effect at 2.5 \u03bcg pNGF). In vivo, the pNGF@NP\/GEL group showed superior TBI healing: higher biomechanical strength (maximum load: 32.7 \u00b1 4.9 N vs 25.5 \u00b1 5.2 N in pEmpty@NP\/GEL;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .026 vs 21.6 \u00b1 5.1 N in control;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001 at 8 weeks), improved bone microarchitecture (higher bone mineral density at 8 weeks;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001), better histologic repair (Modified Histomorphometric Scoring System: 31.3 \u00b1 2.1 vs 25 \u00b1 1 in pEmpty@NP\/GEL;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .015 vs 22.67 \u00b1 2.31 in control;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .003 at 8 weeks), optimized collagen I\/III ratio, and enhanced functional recovery, with only mild neurotrophin-3 upregulation and increased heterotopic ossification (HO) although not in clinically concerning regions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>NGF gene delivery effectively enhances TBI healing in a rat model of acute RCT histologically, structurally, and functionally via NP-GEL composites, accompanied by mild upregulation of NT-3 and increased HO, although not in clinically concerning regions. Thus, this strategy holds translational potential to improve the clinical outcomes of RCTs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>The NGF has translational potential to improve clinical outcomes in RCTs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03635465261449709","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:16:26Z","timestamp":1783487786000},"page":"2286-2299","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Nerve Growth Factor Gene Delivery via Nanosphere-Hydrogel Composites and Tendon-Bone Interface Healing in a Rat Rotator Cuff Tear Model"],"prefix":"10.1177","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8205-2981","authenticated-orcid":false,"given":"Ye","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurou","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Second People's Hospital of Nantong, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Affiliated Hospital of Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxi","family":"Lu","sequence":"additional","affiliation":[{"name":"Medical School of Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Feng","sequence":"additional","affiliation":[{"name":"Medical School of Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Affiliated Hospital of Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Medical School of Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxin","family":"Hu","sequence":"additional","affiliation":[{"name":"Medical School of Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youlang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5899-2792","authenticated-orcid":false,"given":"Yucheng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, 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