{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:01:03Z","timestamp":1790107263844,"version":"4.0.1"},"reference-count":30,"publisher":"American Chemical Society (ACS)","issue":"17","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG2K0021"],"award-info":[{"award-number":["CMRPG2K0021"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 109-2314-B-182A-022-MY2"],"award-info":[{"award-number":["MOST 109-2314-B-182A-022-MY2"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autologous iliac crest bone graft is widely used for spinal fusion, yet its application is limited by donor-site morbidity and finite graft volume. In this study, we developed a highly porous scaffold of magnesium (Mg) combined with \u03b2-tricalcium phosphate (\u03b2-TCP) and gelatin (Mg\/gelatin\/\u03b2-TCP), seeded with adipose-derived mesenchymal stem cells (AdMSCs), and evaluated the effect of Mg content on cell\u2013material responses and bone formation. Scaffolds containing 0, 0.5, 1, and 2% Mg (expressed as w\/v, g of Mg per 100 mL of gelatin solution) were fabricated and tested for Mg release and biological performance. In vitro, AdMSC viability, proliferation, and cytotoxicity were assessed using LIVE\/DEAD staining, Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays, and osteogenic differentiation by alkaline phosphatase (ALP) and osteocalcin immunofluorescence. In vivo, a rat L4\u2013L5 posterolateral fusion model was used with micro-computed tomography (micro-CT) and histology at 2, 4, and 8 weeks. All groups maintained high cell viability with only a small fraction of dead cells; however, at 2% Mg, the surviving cells showed reduced proliferation and elevated LDH release, indicating that a high Mg burden and the accompanying alkaline microenvironment suppress cellular function without causing wholesale cell death. The 1% Mg scaffold produced the strongest early osteogenic signal (peak ALP) while also supporting matrix mineralization and yielded the most favorable micro-CT bone formation, approaching autograft. These results demonstrate that the 1% Mg-modified scaffold maximizes AdMSC osteogenesis without the cytotoxicity seen at 2% Mg, offering a promising alternative for bone tissue engineering and spinal fusion applications.<\/jats:p>","DOI":"10.1021\/acsabm.6c01106","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T17:17:36Z","timestamp":1788196656000},"page":"8241-8253","source":"Crossref","is-referenced-by-count":0,"title":["Optimum Magnesium Enhances Osteogenesis of Adipose-Derived Mesenchymal Stem Cells Implanted in Tricalcium Phosphate-Gelatin Composite for Spine Fusion in Rats"],"prefix":"10.1021","volume":"9","author":[{"given":"Ngi Chiong","family":"Lau","sequence":"first","affiliation":[{"name":"Chang Gung Memorial Hospital , , Keelung Branch , ,","place":["Keelung, Taiwan, 204"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]},{"name":"Chang Gung Memorial Hospital , , Linkou Branch , ,","place":["Taoyuan, Taiwan, 333"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Chih","family":"Wang","sequence":"additional","affiliation":[{"name":"Chang Gung Memorial Hospital , , Keelung Branch , ,","place":["Keelung, Taiwan, 204"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wei","family":"Chang","sequence":"additional","affiliation":[{"name":"Chang Gung Memorial Hospital , , Keelung Branch , ,","place":["Keelung, Taiwan, 204"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tung-Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Chang Gung Memorial Hospital , , Keelung Branch , ,","place":["Keelung, Taiwan, 204"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chak-Bor","family":"Wong","sequence":"additional","affiliation":[{"name":"Chang Gung Memorial Hospital , , Keelung Branch , ,","place":["Keelung, Taiwan, 204"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9051-6045","authenticated-orcid":true,"given":"Tsai-Sheng","family":"Fu","sequence":"additional","affiliation":[{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]},{"name":"Chang Gung University , , ,","place":["Taoyuan, Taiwan, 333"]},{"name":"Chang Gung Memorial Hospital , , Linkou Branch , ,","place":["Taoyuan, Taiwan, 333"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"2026092215071156800_cit1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.jot.2021.11.001","article-title":"Therapeutics for Enhancement of Spinal Fusion: A Mini Review","volume":"31","author":"Zhang","year":"2021","journal-title":"J. Orthop. Translat."},{"key":"2026092215071156800_cit2","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1002\/term.1503","article-title":"Inflammatory Response of Intervertebral Disc Cells Is Reduced by Fibrin Sealant Scaffold in Vitro","volume":"8","author":"Buser","year":"2014","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"2026092215071156800_cit3","doi-asserted-by":"publisher","first-page":"9353","DOI":"10.1021\/nn304773b","article-title":"Designing Biomaterials to Direct Stem Cell Fate","volume":"6","author":"Cha","year":"2012","journal-title":"ACS Nano"},{"key":"2026092215071156800_cit4","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1016\/j.joca.2013.07.016","article-title":"Transplantation of Autologous Endothelial Progenitor Cells in Porous PLGA Scaffolds Create a Microenvironment for the Regeneration of Hyaline Cartilage in Rabbits","volume":"21","author":"Chang","year":"2013","journal-title":"Osteoarthritis Cartilage"},{"issue":"Suppl 2","key":"2026092215071156800_cit5","doi-asserted-by":"publisher","first-page":"289","DOI":"10.2174\/1874325001105010289","article-title":"Tissue Engineering for Bone Production\u2013 Stem Cells, Gene Therapy and Scaffolds","volume":"5","author":"Khaled","year":"2011","journal-title":"Open Orthop. J."},{"key":"2026092215071156800_cit6","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1002\/jbm.b.33016","article-title":"Effect of a \u03b2-TCP Collagen Composite Bone Substitute on Healing of Drilled Bone Voids in the Distal Femoral Condyle of Rabbits","volume":"102","author":"Zheng","year":"2014","journal-title":"J. Biomed. Mater. Res., Part B"},{"key":"2026092215071156800_cit7","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.actbio.2008.09.020","article-title":"Effect of Pore Size on ECM Secretion and Cell Growth in Gelatin Scaffold for Articular Cartilage Tissue Engineering","volume":"5","author":"Lien","year":"2009","journal-title":"Acta Biomater."},{"key":"2026092215071156800_cit8","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1007\/s10439-014-1207-1","article-title":"Biomaterials for Integration with 3-D Bioprinting","volume":"43","author":"Skardal","year":"2015","journal-title":"Ann. Biomed. Eng."},{"key":"2026092215071156800_cit9","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.jfma.2017.01.005","article-title":"Bone Morphogenetic Protein-2 Loaded Poly(D,L-lactide-co-glycolide) Microspheres Enhance Osteogenic Potential of Gelatin\/Hydroxyapatite\/\u03b2-Tricalcium Phosphate Cryogel Composite for Alveolar Ridge Augmentation","volume":"116","author":"Chang","year":"2017","journal-title":"J. Formos. Med. Assoc."},{"key":"2026092215071156800_cit10","doi-asserted-by":"publisher","first-page":"427","DOI":"10.3233\/BME-181000","article-title":"Magnesium Doping on TiN Coatings Affects Mesenchymal Stem Cell Differentiation and Proliferation Positively in a Dose-Dependent Manner","volume":"29","author":"Onder","year":"2018","journal-title":"Biomed. Mater. Eng."},{"key":"2026092215071156800_cit11","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1002\/jbm.b.33113","article-title":"Magnesium Biomaterials for Orthopedic Application: A Review from a Biological Perspective","volume":"102","author":"Walker","year":"2014","journal-title":"J. Biomed. Mater. Res., Part B"},{"key":"2026092215071156800_cit12","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.msec.2016.11.027","article-title":"Porous Magnesium-Based Scaffolds for Tissue Engineering","volume":"71","author":"Yazdimamaghani","year":"2017","journal-title":"Mater. Sci. Eng., C"},{"key":"2026092215071156800_cit13","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1097\/SCS.0000000000005447","article-title":"Review of the Pathways Involved in the Osteogenic Differentiation of Adipose-Derived Stem Cells","volume":"30","author":"Asserson","year":"2019","journal-title":"J. Craniofac. Surg."},{"key":"2026092215071156800_cit14","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.tibtech.2006.01.010","article-title":"Fat Tissue: An Underappreciated Source of Stem Cells for Biotechnology","volume":"24","author":"Fraser","year":"2006","journal-title":"Trends Biotechnol."},{"key":"2026092215071156800_cit15","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.bbrc.2005.04.135","article-title":"Human Adipose Tissue-Derived Stem Cells Differentiate into Endothelial Cells in Vitro and Improve Postnatal Neovascularization in Vivo","volume":"332","author":"Cao","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026092215071156800_cit16","doi-asserted-by":"publisher","first-page":"360","DOI":"10.3390\/ijms19020360","article-title":"Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment","volume":"19","author":"Hu","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2026092215071156800_cit17","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1161\/01.CIR.0000121425.42966.F1","article-title":"Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells","volume":"109","author":"Rehman","year":"2004","journal-title":"Circulation"},{"key":"2026092215071156800_cit18","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jss.2009.07.021","article-title":"A Novel Cell-Based Therapy in Segmental Bone Defect: Using Adipose Derived Stromal Cells","volume":"168","author":"Zou","year":"2011","journal-title":"J. Surg. Res."},{"key":"2026092215071156800_cit19","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1089\/107632701300062859","article-title":"Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies","volume":"7","author":"Zuk","year":"2001","journal-title":"Tissue Eng."},{"key":"2026092215071156800_cit20","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s40824-020-00196-1","article-title":"In Vivo Bone Regeneration Assessment of Offset and Gradient Melt Electrowritten (MEW) PCL Scaffolds","volume":"24","author":"Abbasi","year":"2020","journal-title":"Biomater. Res."},{"key":"2026092215071156800_cit21","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jot.2019.04.007","article-title":"Surface Degradation-Enabled Osseointegrative, Angiogenic and Antiinfective Properties of Magnesium-Modified Acrylic Bone Cement","volume":"17","author":"Lin","year":"2019","journal-title":"J. Orthop. Translat."},{"key":"2026092215071156800_cit22","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1089\/ten.TEA.2020.0350","article-title":"Recent Advances on Bioprinted Gelatin Methacrylate-Based Hydrogels for Tissue Repair","volume":"27","author":"Rajabi","year":"2021","journal-title":"Tissue Eng., Part A"},{"key":"2026092215071156800_cit23","doi-asserted-by":"publisher","DOI":"10.1088\/2752-5724\/ad9493","article-title":"Overview of Porous Magnesium-Based Scaffolds: Development, Properties and Biomedical Applications","volume":"4","author":"Motaharinia","year":"2025","journal-title":"Mater. Futures"},{"key":"2026092215071156800_cit24","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1007\/s10529-015-1907-0","article-title":"Recent Advances in the Use of Gelatin in Biomedical Research","volume":"37","author":"Su","year":"2015","journal-title":"Biotechnol. Lett."},{"key":"2026092215071156800_cit25","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1007\/s10856-016-5763-9","article-title":"Evaluation of Cell Binding to Collagen and Gelatin: A Study of the Effect of 2D and 3D Architecture and Surface Chemistry","volume":"27","author":"Davidenko","year":"2016","journal-title":"J. Mater. Sci.: Mater. Med."},{"key":"2026092215071156800_cit26","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s13770-019-00192-0","article-title":"Three-Dimensional Printed Mg-Doped \u03b2-TCP Bone Tissue Engineering Scaffolds: Effects of Magnesium Ion Concentration on Osteogenesis and Angiogenesis In Vitro","volume":"16","author":"Gu","year":"2019","journal-title":"Tissue Eng. Regen. Med."},{"key":"2026092215071156800_cit27","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1089\/ten.TEA.2011.0310","article-title":"Magnesium Calcium Phosphate as a Novel Component Enhances Mechanical\/Physical Properties of Gelatin Scaffold and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells","volume":"18","author":"Hussain","year":"2012","journal-title":"Tissue Eng., Part A"},{"key":"2026092215071156800_cit28","doi-asserted-by":"publisher","first-page":"7758","DOI":"10.1021\/acsabm.4c01420","article-title":"Biphasic Calcium Phosphate Ceramic Scaffold Composed of Zinc Doped \u03b2-Tricalcium Phosphate and Silicon Doped Hydroxyapatite for Bone Tissue Engineering","volume":"7","author":"Fan","year":"2024","journal-title":"ACS Appl. Bio Mater."},{"key":"2026092215071156800_cit29","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1021\/acsbiomaterials.0c01719","article-title":"Effect of Dual Pore Size Architecture on In Vitro Osteogenic Differentiation in Additively Manufactured Hierarchical Scaffolds","volume":"7","author":"Ratheesh","year":"2021","journal-title":"ACS Biomater. Sci. Eng."},{"key":"2026092215071156800_cit30","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1210\/edrv-14-4-424","article-title":"Molecular Mechanisms Mediating Proliferation\/Differentiation Interrelationships During Progressive Development of the Osteoblast Phenotype","volume":"14","author":"Stein","year":"1993","journal-title":"Endocr. Rev."}],"container-title":["ACS Applied Bio Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsabm.6c01106","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/9\/17\/8241\/67377084\/mt-2026-01106t.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/9\/17\/8241\/67377084\/mt-2026-01106t.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:09:11Z","timestamp":1790104151000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article\/9\/17\/8241\/5326692\/Optimum-Magnesium-Enhances-Osteogenesis-of-Adipose"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":30,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,8,24]]},"published-print":{"date-parts":[[2026,9,7]]}},"URL":"https:\/\/doi.org\/10.1021\/acsabm.6c01106","relation":{},"ISSN":["2576-6422"],"issn-type":[{"value":"2576-6422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]}}}