{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:34:40Z","timestamp":1779136480016,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Efficient bone repair relies on both osteogenic and angiogenic signals, with growth factors playing a pivotal role. Despite decades of recognition of their therapeutic potential, the optimal dosages and delivery routes of growth factors still require extensive investigation. Previous research demonstrated the osteoinductive and angiogenic potential of growth factors. However, effective therapeutic outcomes depend on precise dosing and prolonged delivery. This study investigates the dual delivery of key growth factors, bone morphogenetic protein\u20102 (BMP\u20102) and vascular endothelial growth factor (VEGF), providing insights into their optimal dosages and delivery mechanisms. The combination of these growth factors may enhance scaffold\u2010mediated bone regeneration in the early stages of healing. This study employed a dual delivery system using BMP\u20102 and VEGF, comparing two methods to determine the optimal dosage and delivery strategy. The combined effect indicates that sustained delivery is a more efficient method. Osteogenesis and angiogenesis were examined in an interpenetrating network (IPN) hydrogel composed of alginate and polyethylene diacrylate (PEGDA), which encapsulated preosteoblast MC3T3 cells. The findings of this study reveal significant increases in alkaline phosphatase (ALP) activity and calcium content, emphasizing the effectiveness of this approach. Biomaterial characterization, including swelling measurements, Fourier transform infrared (FTIR) spectroscopy, confirmed growth factor encapsulation, and a release assay validated the delivery process. Compared to direct delivery, sustained delivery increased ALP activity and calcium release by up to 1.12\u2010 and 1.85\u2010fold, respectively. Molecular studies indicated that sustained delivery of both growth factors had a stronger osteoinductive and angiogenic effect than direct delivery. This research evaluates the effects of growth factor delivery in a 3D hydrogel\u2010based microenvironment using hydrogels and compares delivery methods to identify a more effective strategy for bone healing.<\/jats:p>","DOI":"10.1002\/jbm.a.37947","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T16:34:48Z","timestamp":1749659688000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Microsphere\u2010Mediated Sustained Delivery of Growth Factors Stimulates Osteogenesis in Target Cells in a Three\u2010Dimensional Microenvironment"],"prefix":"10.1002","volume":"113","author":[{"given":"Ketki","family":"Holkar","sequence":"first","affiliation":[{"name":"Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis School of Biological Sciences (SSBS) Symbiosis International (Deemed University)  Pune India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prasad","family":"Pethe","sequence":"additional","affiliation":[{"name":"Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis School of Biological Sciences (SSBS) Symbiosis International (Deemed University)  Pune India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaijayanti","family":"Kale","sequence":"additional","affiliation":[{"name":"Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis School of Biological Sciences (SSBS) Symbiosis International (Deemed University)  Pune India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ganesh","family":"Ingavle","sequence":"additional","affiliation":[{"name":"Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis School of Biological Sciences (SSBS) Symbiosis International (Deemed University)  Pune India"},{"name":"Clinical Research Facility, NIHR Biomedical Research Centre Guy's &amp; st Thomas' NHS Foundation Trust and King's College London, Guy's Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.04.004"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.6b01407"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.21-1-118"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2005.05.303"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.3.513"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano13152185"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/17435889.2025.2457317"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2014.08.011"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.07.058"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2013.12.023"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1BM01521D"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S423985"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121721"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152324099"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2006.02.039"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01657"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.200386"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v019a04"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1360"},{"issue":"10","key":"e_1_2_10_21_1","first-page":"1434","article-title":"Recombinant Human Vascular Endothelial Growth Factor Enhances Bone Healing in an Experimental Nonunion Model","volume":"87","author":"Eckardt H.","year":"2005","journal-title":"Journal of Bone and Joint Surgery. British Volume"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2010.0223"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.9790\/3013-24204448"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym3010571"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2014.11.021"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2021.1943056"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2024.12.006"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevBiomedEng.v40.i5.10"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-1041fje"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.3c00058"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2009.0761"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2012.0288"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/mps3020030"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01704-9"}],"container-title":["Journal of Biomedical Materials Research Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.37947","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T09:51:44Z","timestamp":1754905904000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.a.37947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":33,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jbm.a.37947"],"URL":"https:\/\/doi.org\/10.1002\/jbm.a.37947","archive":["Portico"],"relation":{},"ISSN":["1549-3296","1552-4965"],"issn-type":[{"value":"1549-3296","type":"print"},{"value":"1552-4965","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2025-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e37947"}}