{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:34:13Z","timestamp":1792787653981,"version":"4.5.0"},"reference-count":39,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Grant of Peak Climbing Project of Foshan Hospital of Traditional Chinese Medicine","award":["202000190"],"award-info":[{"award-number":["202000190"]}],"id":[{"id":"https:\/\/ror.org\/01dw0ab98","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Biomater Appl"],"abstract":"<jats:p>Critical-sized bone defects exceed bone\u2019s regenerative capacity and require space-maintaining implants that support vascular and bone-tissue ingrowth. Three-dimensional (3D)-printed polycaprolactone (PCL) scaffolds are widely investigated for bone repair owing to controllable geometry, interconnected macropores, and structural stability. However, uniform-pore designs cannot recapitulate heterogeneous bone porosity, while hydrophobic PCL has limited bioactivity. Inspired by the transition from dense cortical to porous cancellous bone, we designed a stepwise gradient-pore PCL framework combining compact regions for structural support with progressively more open regions, providing multiple cell- and tissue-relevant environments. An in situ photocrosslinked methacrylated chondroitin sulfate (CSMA) hydrogel containing bone morphogenetic protein-2 (BMP-2) and the vascular endothelial growth factor-mimetic QK peptide was formed within the printed pores as a hydrated delivery phase. The scaffold retained sequential dense, intermediate, and loose regions; CSMA improved wettability; and PCL confinement slowed the release of both factors relative to hydrogel alone, with QK reaching approximately 80% cumulative release by day 14 and BMP-2 approximately 65% by day 28. Relative to PCL and PCL-CSMA, PCL-CSMA-QK-BMP enhanced endothelial responses, rat bone marrow mesenchymal stem cell proliferation and migration, and osteogenic differentiation and mineralization. Single-factor comparisons supported QK-related endothelial and BMP-2-related osteogenic effects. In rat calvarial defects, PCL-CSMA-QK-BMP increased bone volume fraction, trabecular number, bone mineral density, collagen-rich matrix deposition, and osteogenic and angiogenesis-associated marker expression at 4 and 8\u00a0weeks relative to PCL and PCL-CSMA. These findings support coupling graded macroporosity with a hydrated delivery phase for vascularized bone regeneration.<\/jats:p>","DOI":"10.1177\/08853282261492945","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:55:13Z","timestamp":1790704513000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Revitalizing bioinert PCL: A biomimetic 3D-Printed gradient-pore scaffold with CSMA hydrogel-mediated BMP-2\/QK delivery for vascularized bone regeneration"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4561-7470","authenticated-orcid":false,"given":"Zekun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Stomatology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China"},{"name":"College of Chemistry and Materials Science","place":["China"]},{"name":"Jinan University","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5811-967X","authenticated-orcid":false,"given":"Chunjiao","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science","place":["China"]},{"name":"Jinan University","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8136-3471","authenticated-orcid":false,"given":"Wenbin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-0928","authenticated-orcid":false,"given":"Shikun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25116012"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-021-00180-y"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12938-025-01381-w"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2025.1707406"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/jfb15090243"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jobcr.2019.10.003"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1168504"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-15602-y"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2006.11.024"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.09.063"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2018.0119"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2024.1444986"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1252636"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep22898"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.4c06820"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.37235"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.18-0141"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25040978"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8TB03020K"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2017.00068"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093242"},{"key":"e_1_3_6_23_2","first-page":"123","article-title":"BMP-2 promotes osteogenic differentiation of mesenchymal stem cells by enhancing mitochondrial activity","volume":"22","author":"Li Y","year":"2022","unstructured":"Li Y, Fu G, Gong Y, et al. 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