{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T18:40:29Z","timestamp":1775500829493,"version":"3.50.1"},"reference-count":80,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:00:00Z","timestamp":1748649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Beijing, China","award":["7232119"],"award-info":[{"award-number":["7232119"]}]},{"name":"Natural Science Foundation of Beijing, China","award":["82102582"],"award-info":[{"award-number":["82102582"]}]},{"name":"Natural Science Foundation of Beijing, China","award":["UHB11847"],"award-info":[{"award-number":["UHB11847"]}]},{"name":"Natural Science Foundation of Beijing, China","award":["2022-PUMCH-C-036"],"award-info":[{"award-number":["2022-PUMCH-C-036"]}]},{"name":"Natural Science Foundation of Beijing, China","award":["2023-I2M-C&T-B-002"],"award-info":[{"award-number":["2023-I2M-C&T-B-002"]}]},{"name":"National Natural Science Foundation Youth Fund","award":["7232119"],"award-info":[{"award-number":["7232119"]}]},{"name":"National Natural Science Foundation Youth Fund","award":["82102582"],"award-info":[{"award-number":["82102582"]}]},{"name":"National Natural Science Foundation Youth Fund","award":["UHB11847"],"award-info":[{"award-number":["UHB11847"]}]},{"name":"National Natural Science Foundation Youth Fund","award":["2022-PUMCH-C-036"],"award-info":[{"award-number":["2022-PUMCH-C-036"]}]},{"name":"National Natural Science Foundation Youth Fund","award":["2023-I2M-C&T-B-002"],"award-info":[{"award-number":["2023-I2M-C&T-B-002"]}]},{"name":"Peking Union Medical College Hospital Talent Cultivation Program","award":["7232119"],"award-info":[{"award-number":["7232119"]}]},{"name":"Peking Union Medical College Hospital Talent Cultivation Program","award":["82102582"],"award-info":[{"award-number":["82102582"]}]},{"name":"Peking Union Medical College Hospital Talent Cultivation Program","award":["UHB11847"],"award-info":[{"award-number":["UHB11847"]}]},{"name":"Peking Union Medical College Hospital Talent Cultivation Program","award":["2022-PUMCH-C-036"],"award-info":[{"award-number":["2022-PUMCH-C-036"]}]},{"name":"Peking Union Medical College Hospital Talent Cultivation Program","award":["2023-I2M-C&T-B-002"],"award-info":[{"award-number":["2023-I2M-C&T-B-002"]}]},{"name":"National High-Level Hospital Clinical Research Funding","award":["7232119"],"award-info":[{"award-number":["7232119"]}]},{"name":"National High-Level Hospital Clinical Research Funding","award":["82102582"],"award-info":[{"award-number":["82102582"]}]},{"name":"National High-Level Hospital Clinical Research Funding","award":["UHB11847"],"award-info":[{"award-number":["UHB11847"]}]},{"name":"National High-Level Hospital Clinical Research Funding","award":["2022-PUMCH-C-036"],"award-info":[{"award-number":["2022-PUMCH-C-036"]}]},{"name":"National High-Level Hospital Clinical Research Funding","award":["2023-I2M-C&T-B-002"],"award-info":[{"award-number":["2023-I2M-C&T-B-002"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["7232119"],"award-info":[{"award-number":["7232119"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["82102582"],"award-info":[{"award-number":["82102582"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["UHB11847"],"award-info":[{"award-number":["UHB11847"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2022-PUMCH-C-036"],"award-info":[{"award-number":["2022-PUMCH-C-036"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2023-I2M-C&T-B-002"],"award-info":[{"award-number":["2023-I2M-C&T-B-002"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering"],"abstract":"<jats:p>(1) Background: Osteonecrosis of the femoral head (ONFH), caused by insufficient blood supply, leads to bone tissue death. Current treatments lack effective bone regeneration materials to reverse disease progression. This study introduces an injectable and self-setting 3D porous bioceramic scaffold (Mg@Ca), combining MgO + SiO2 mixtures with \u03b1-hemihydrate calcium sulfate, designed to promote bone repair through in situ pore formation and osteoinduction. (2) Methods: In vitro experiments evaluated human bone marrow mesenchymal stem cell (h-BMSC) proliferation, differentiation, and osteogenic marker expression in Mg@Ca medium. Transcriptome sequencing identified bone development-related pathways. In vivo efficacy was assessed in a rabbit model of ONFH to evaluate bone repair. (3) Results: The Mg@Ca scaffold demonstrated excellent biocompatibility and supported h-BMSC proliferation and differentiation, with significant up-regulation of COL1A1 and BGLAP. Transcriptome analysis revealed activation of the PI3K-Akt signaling pathway, critical for osteogenesis. In vivo results confirmed enhanced trabecular density and bone volume compared to controls, indicating effective bone repair and regeneration. (4) Conclusions: The Mg@Ca scaffold offers a promising therapeutic approach for ONFH, providing a minimally invasive solution for bone defect repair while stimulating natural bone regeneration. Its injectable and self-setting properties ensure precise filling of bone defects, making it suitable for clinical applications.<\/jats:p>","DOI":"10.3390\/bioengineering12060599","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Injectable and Assembled Calcium Sulfate\/Magnesium Silicate 3D Scaffold Promotes Bone Repair by In Situ Osteoinduction"],"prefix":"10.3390","volume":"12","author":[{"given":"Wei","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Orthopedics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"Centro M\u00e9dico de Macau do Peking Union Medical College Hospital, Macau 999078, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0035-7563","authenticated-orcid":false,"given":"Tianhao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1834-8662","authenticated-orcid":false,"given":"Guangli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixin","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xia","sequence":"additional","affiliation":[{"name":"Applied Materials Science, Department of Materials Science and Engineering, Uppsala University, 752 37 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xisheng","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1054\/arth.2002.33300","article-title":"Osteonecrosis\u2014Avoiding total hip arthroplasty","volume":"17","author":"Hungeford","year":"2002","journal-title":"J. Arthroplast."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s11999-013-3220-3","article-title":"Treatment of Femoral Head Osteonecrosis in the United States: 16-year Analysis of the Nationwide Inpatient Sample","volume":"472","author":"Johnson","year":"2014","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3109\/14397595.2014.932038","article-title":"Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan","volume":"25","author":"Ikeuchi","year":"2015","journal-title":"Mod. Rheumatol."},{"key":"ref_4","first-page":"100","article-title":"Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version)","volume":"21","author":"Zhao","year":"2020","journal-title":"J. Orthop. Transl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"477","DOI":"10.2106\/JBJS.F.01582","article-title":"Fate of untreated asymptomatic osteonecrosis of the femoral head","volume":"90A","author":"Nam","year":"2008","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_6","first-page":"26","article-title":"Avascular Necrosis of the Hip","volume":"55","author":"Ozcakir","year":"2009","journal-title":"Turk. Fiz. Tip Ve Rehabil. Derg. Turk. J. Phys. Med. Rehabil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.2106\/JBJS.19.01271","article-title":"Nontraumatic Osteonecrosis of the Femoral Head: Where Do We Stand Today? A 5-Year Update","volume":"102","author":"Mont","year":"2020","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"54","DOI":"10.2106\/JBJS.20.00527","article-title":"Core Decompression and Bone Marrow Aspiration Concentrate Grafting for Osteonecrosis of the Femoral Head","volume":"104","author":"Hoogervorst","year":"2022","journal-title":"J. Bone Jt. Surg. Am. Vol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Thanh Ngoc, T., Wolf, M., Winter, P., and Landgraeber, S. (2022). Hip joint mechanics in patients with osteonecrosis of the femoral head following treatment by advanced core decompression. Clin. Biomech., 94.","DOI":"10.1016\/j.clinbiomech.2022.105635"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s002640000186","article-title":"Failure after core decompression in osteonecrosis of the femoral head","volume":"24","author":"Yoon","year":"2001","journal-title":"Int. Orthop."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/01.blo.0000069005.56218.57","article-title":"Osteonecrosis after powered core decompression","volume":"412","author":"Mihalko","year":"2003","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.12669\/pjms.36.6.2176","article-title":"Repair of non-traumatic femoral head necrosis by marrow core decompression with bone grafting and porous tantalum rod implantation","volume":"36","author":"Peng","year":"2020","journal-title":"Pak. J. Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1186\/s13018-020-01867-4","article-title":"Biomechanical analysis of fibular graft techniques for nontraumatic osteonecrosis of the femoral head: A finite element analysis","volume":"15","author":"Xu","year":"2020","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/micr.20837","article-title":"Femoral head osteonecrosis: Why choose free vascularized fibula grafting","volume":"31","author":"Korompilias","year":"2011","journal-title":"Microsurgery"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13018-021-02246-3","article-title":"Long-term survival and clinical outcomes of non-vascularized autologous and allogeneic fibular grafts are comparable for treating osteonecrosis of the femoral head","volume":"16","author":"Jie","year":"2021","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_16","first-page":"495","article-title":"Reconstructing avascular necrotic femoral head through a bioactive \u03b2-TCP system: From design to application","volume":"28","author":"Lu","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"110997","DOI":"10.1016\/j.eurpolymj.2022.110997","article-title":"New way to obtain the poly(L-lactide-co-D,L-lactide) blend filled with nanohydroxyapatite as biomaterial for 3D-printed bone-reconstruction implants","volume":"165","author":"Targonska","year":"2022","journal-title":"Eur. Polym. J."},{"key":"ref_18","first-page":"69","article-title":"Meticulously engineered three-dimensional-printed scaffold with microarchitecture and controlled peptide release for enhanced bone regeneration","volume":"5","author":"Yang","year":"2024","journal-title":"Biomater. Transl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jcis.2021.04.025","article-title":"3D printable magnesium-based cements towards the preparation of bioceramics","volume":"598","author":"Tonelli","year":"2021","journal-title":"J. Colloid Interface Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Han, Y., Wei, Q., Chang, P., Hu, K., Okoro, O.V., Shavandi, A., and Nie, L. (2021). Three-Dimensional Printing of Hydroxyapatite Composites for Biomedical Application. Crystals, 11.","DOI":"10.3390\/cryst11040353"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yue, X., Zhao, L., Yang, J., Jiao, X., Wu, F., Zhang, Y., Li, Y., Qiu, J., Ke, X., and Sun, X. (2023). Comparison of osteogenic capability of 3D-printed bioceramic scaffolds and granules with different porosities for clinical translation. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1260639"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s42242-019-00046-7","article-title":"3D printing of calcium phosphate bioceramic with tailored biodegradation rate for skull bone tissue reconstruction","volume":"2","author":"Zhang","year":"2019","journal-title":"Bio-Des. Manuf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/jbm.b.31269","article-title":"Calcium Sulfate: Properties and Clinical Applications","volume":"88B","author":"Thomas","year":"2009","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1615\/JLongTermEffMedImplants.v15.i6.30","article-title":"Calcium sulfate: A review","volume":"15","author":"Thomas","year":"2005","journal-title":"J. Long-Term Eff. Med. Implant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1563\/aaid-joi-D-18-00306","article-title":"Biphasic Calcium Sulfate as an Alternative Grafting Material in Various Dental Applications","volume":"45","author":"Baranes","year":"2019","journal-title":"J. Oral Implantol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nicoara, A.I., Voineagu, T.G., Alecu, A.E., Vasile, B.S., Maior, I., Cojocaru, A., Trusca, R., and Popescu, R.C. (2023). Fabrication and Characterisation of Calcium Sulphate Hemihydrate Enhanced with Zn- or B-Doped Hydroxyapatite Nanoparticles for Hard Tissue Restoration. Nanomaterials, 13.","DOI":"10.3390\/nano13152219"},{"key":"ref_27","first-page":"e24408","article-title":"Effectiveness of Calcium Sulfate and Hydroxyapatite Composite in Collapse Prevention in Osteonecrosis of Femoral Head","volume":"14","author":"Jameel","year":"2022","journal-title":"Cureus J. Med. Sci."},{"key":"ref_28","first-page":"2926","article-title":"Calcium sulfate as bone graft substitute in the treatment of osseous bone defects, a prospective study","volume":"7","author":"Kumar","year":"2013","journal-title":"J. Clin. Diagn. Res. JCDR"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Georgeanu, V.A., Gingu, O., Antoniac, I.V., and Manolea, H.O. (2023). Current Options and Future Perspectives on Bone Graft and Biomaterials Substitutes for Bone Repair, from Clinical Needs to Advanced Biomaterials Research. Appl. Sci., 13.","DOI":"10.3390\/app13148471"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chen, I.C., Su, C.-Y., Lai, C.-C., Tsou, Y.-S., Zheng, Y., and Fang, H.-W. (2021). Preparation and Characterization of Moldable Demineralized Bone Matrix\/Calcium Sulfate Composite Bone Graft Materials. J. Funct. Biomater., 12.","DOI":"10.3390\/jfb12040056"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1177\/0885328219849712","article-title":"Cerium-containing \u03b1-calcium sulfate hemihydrate bone substitute promotes osteogenesis","volume":"34","author":"Xiang","year":"2019","journal-title":"J. Biomater. Appl."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chiang, C.-C., Hsieh, M.-K., Wang, C.-Y., Tuan, W.-H., and Lai, P.-L. (2021). Cytotoxicity and cell response of preosteoblast in calcium sulfate-augmented PMMA bone cement. Biomed. Mater., 16.","DOI":"10.1088\/1748-605X\/ac1ab5"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1166\/mex.2021.2060","article-title":"Assessment of \u03b1-calcium sulfate hemihydrate\/nanocellulose composite bone graft material for bone healing in a rabbit femoral condyle model","volume":"11","author":"Liu","year":"2021","journal-title":"Mater. Express"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.clinbiomech.2019.03.008","article-title":"Fracture strength of the proximal femur injected with a calcium sulfate\/hydroxyapatite bone substitute","volume":"63","author":"Kok","year":"2019","journal-title":"Clin. Biomech."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1002\/jbm.b.34671","article-title":"Calcium sulfate-containing glass polyalkenoate cement for revision total knee arthroplasty fixation","volume":"108","author":"Hasandoost","year":"2020","journal-title":"J. Biomed. Mater. Res. Part B-Appl. Biomater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e20563","DOI":"10.1097\/MD.0000000000020563","article-title":"Injectable calcium sulfate vs mixed bone graft of autologous iliac bone and allogeneic bone. Which is the better bone graft material for unicameral bone cyst in humerus?","volume":"99","author":"Li","year":"2020","journal-title":"Medicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s10856-020-06441-2","article-title":"The effects of oyster shell\/alpha-calcium sulfate hemihydrate\/platelet-rich plasma\/bone mesenchymal stem cells bioengineering scaffold on rat critical-sized calvarial defects","volume":"31","author":"Wang","year":"2020","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhang, T., Zou, J., Wang, B., Wu, Z., Jia, Y., and Cheeseman, C.R. (2018). Characterization of Magnesium Silicate Hydrate (MSH) Gel Formed by Reacting MgO and Silica Fume. Materials, 11.","DOI":"10.3390\/ma11060909"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yoo, K.-H., Kim, Y.-I., and Yoon, S.-Y. (2021). Physicochemical and Biological Properties of Mg-Doped Calcium Silicate Endodontic Cement. Materials, 14.","DOI":"10.3390\/ma14081843"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6299","DOI":"10.1016\/j.biomaterials.2014.04.044","article-title":"The effect of metallic magnesium degradation products on osteoclast-induced osteolysis and attenuation of NF-\u03baB and NFATc1 signaling","volume":"35","author":"Zhai","year":"2014","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1002\/jbm.b.35246","article-title":"Alkaline earth metals for osteogenic scaffolds: From mechanisms to applications","volume":"111","author":"Weng","year":"2023","journal-title":"J. Biomed. Mater. Res. Part B-Appl. Biomater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/prd.12533","article-title":"Ion incorporation into bone grafting materials","volume":"94","author":"Zhao","year":"2024","journal-title":"Periodontology 2000"},{"key":"ref_43","first-page":"3","article-title":"Advances in magnesium-containing bioceramics for bone repair","volume":"5","author":"Qi","year":"2024","journal-title":"Biomater. Transl."},{"key":"ref_44","first-page":"408","article-title":"Effects of bone-resorptive lesion on stress distribution of the femoral head and on progression in patients with osteonecrosis of the femoral head","volume":"40","author":"Liu","year":"2020","journal-title":"Chin. J. Orthop."},{"key":"ref_45","first-page":"159","article-title":"3-D microarchitectural properties and rod- and plate-like trabecular morphometric properties of femur head cancellous bones in patients with rheumatoid arthritis, osteoarthritis, and osteoporosis","volume":"28","author":"Ding","year":"2021","journal-title":"J. Orthop. Transl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100823","DOI":"10.1016\/j.apmt.2020.100823","article-title":"Injectable and assembled 3D solid structure for free-to-fixed shape in bone reconstruction","volume":"21","author":"Zhu","year":"2020","journal-title":"Appl. Mater. Today"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1016\/j.arth.2020.04.092","article-title":"Diagnosis of Osteonecrosis of the Femoral Head: Too Little, Too Late, and Independent of Etiology","volume":"35","author":"Boontanapibul","year":"2020","journal-title":"J. Arthroplast."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.arthro.2024.04.002","article-title":"The Principles of Hip Joint Preservation","volume":"40","author":"Kraeutler","year":"2024","journal-title":"Arthrosc. J. Arthrosc. Relat. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/j.arth.2016.12.049","article-title":"Evidence for the Use of Cell-Based Therapy for the Treatment of Osteonecrosis of the Femoral Head: A Systematic Review of the Literature","volume":"32","author":"Piuzzi","year":"2017","journal-title":"J. Arthroplast."},{"key":"ref_50","first-page":"846","article-title":"Cartilage-on-chip for osteoarthritis drug screening","volume":"1","author":"Zhao","year":"2025","journal-title":"Orig. Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wu, D.Y., Wang, S.S., and Wu, C.S. (2023). A new composite fabricated from hydroxyapatite, gelatin-MgO microparticles, and compatibilized poly(butylene succinate) with osteogenic functionality. Biomater. Adv., 154.","DOI":"10.1016\/j.bioadv.2023.213586"},{"key":"ref_52","first-page":"280","article-title":"Fabrication of magnesium-doped porous polylactic acid microsphere for bone regeneration","volume":"4","author":"Tao","year":"2023","journal-title":"Biomater. Transl."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"368","DOI":"10.2109\/jcersj2.22144","article-title":"Effects of magnesium ion supplement on physicochemical properties and bioactivities of medical bone materials converted from oyster shell","volume":"131","author":"Lin","year":"2023","journal-title":"J. Ceram. Soc. Jpn."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Liu, X.S., Pei, J., Zhao, D.C., and Yan, Y.G. (2024). A novel strategy for calcium magnesium phosphate\/carboxymethyl chitosan composite bone cements with enhanced physicochemical properties, excellent cytocompatibility and osteogenic differentiation. Biomed. Mater., 19.","DOI":"10.1088\/1748-605X\/ad5e2a"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1684\/mrh.2023.0518","article-title":"Short-term dietary magnesium deficiency downregulates the expression of bone formation-related genes in rats","volume":"36","author":"Katsumata","year":"2023","journal-title":"Magnes. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Duan, H., Cao, C., Wang, X., Tao, J., Li, C., Xin, H., Yang, J., Song, Y., and Ai, F. (2020). Magnesium-alloy rods reinforced bioglass bone cement composite scaffolds with cortical bone-matching mechanical properties and excellent osteoconductivity for load-bearing bone in vivo regeneration. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-75328-7"},{"key":"ref_57","first-page":"171","article-title":"Morphological and Molecular Analysis of Osteoblasts Differentiated from Mesenchymal Stem Cells in Polycaprolactone\/Magnesium Oxide\/Graphene Oxide Scaffold","volume":"10","author":"Niknam","year":"2019","journal-title":"Int. J. Organ Transplant. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wu, Q., Xu, S., Wang, F., He, B., Wang, X., Sun, Y., Ning, C., and Dai, K. (2021). Double-edged effects caused by magnesium ions and alkaline environment regulate bioactivities of magnesium-incorporated silicocarnotite in vitro. Regen. Biomater., 8.","DOI":"10.1093\/rb\/rbab016"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"621","DOI":"10.33549\/physiolres.932973","article-title":"Polymorphisms Associated With Low Bone Mass and High Risk of Atraumatic Fracture","volume":"64","author":"Zofkova","year":"2015","journal-title":"Physiol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"100757","DOI":"10.1016\/j.diff.2024.100757","article-title":"Type 1 collagen: Synthesis, structure and key functions in bone mineralization","volume":"136","author":"Selvaraj","year":"2024","journal-title":"Differentiation"},{"key":"ref_61","first-page":"2432","article-title":"The Role of Osteocalcin in Patients with Osteoporosis: A Systematic Review","volume":"53","author":"Mohammadi","year":"2024","journal-title":"Iran. J. Public Health"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"117238","DOI":"10.1016\/j.bone.2024.117238","article-title":"The role of bone in energy metabolism: A focus on osteocalcin","volume":"188","author":"Smith","year":"2024","journal-title":"Bone"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"399","DOI":"10.3803\/EnM.2023.1895","article-title":"Osteocalcin: Beyond Bones","volume":"39","author":"Nowicki","year":"2024","journal-title":"Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1177\/1535370215625471","article-title":"BDKRB2+9\/\u22129 bp polymorphisms influence BDKRB2 expression levels and NO production in knee osteoarthritis","volume":"242","author":"Chen","year":"2017","journal-title":"Exp. Biol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chen, S., Zhou, Y., Li, J., Shan, L.Q., and Fan, Q.Y. (2012). The Effect of Bradykinin B2 Receptor Polymorphisms on the Susceptibility and Severity of Osteoarthritis in a Chinese Cohort. J. Biomed. Biotechnol., 2012.","DOI":"10.1155\/2012\/597637"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"116200","DOI":"10.1016\/j.bone.2021.116200","article-title":"Macrophages are requisite for angiogenesis of type H vessels during bone regeneration in mice","volume":"154","author":"Kohara","year":"2022","journal-title":"Bone"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Toor, S.M., Wani, S., and Albagha, O.M.E. (2021). Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.781272"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"179","DOI":"10.5603\/FHC.a2022.0012","article-title":"Identification of candidate genes simultaneously shared by adipogenesis and osteoblastogenesis from human mesenchymal stem cells","volume":"60","author":"Yi","year":"2022","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e22530","DOI":"10.1096\/fj.202200339RRR","article-title":"Controlled mechanical loading improves bone regeneration by regulating type H vessels in a S1Pr1-dependent manner","volume":"36","author":"Yang","year":"2022","journal-title":"Faseb J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e70011","DOI":"10.1096\/fj.202400991R","article-title":"SCUBE3 promotes osteogenic differentiation and mitophagy in human bone marrow mesenchymal stem cells through the BMP2\/TGF-\u03b2 signaling pathway","volume":"38","author":"Chen","year":"2024","journal-title":"Faseb J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"104888","DOI":"10.1016\/j.arabjc.2023.104888","article-title":"A functional polymorphism at the miR-25-3p binding site in the 30-untranslated region of the S1PR1 gene decreases the risk of osteoporosis in Chinese postmenopausal women","volume":"16","author":"Yang","year":"2023","journal-title":"Arab. J. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"918","DOI":"10.5114\/aoms\/171785","article-title":"Enhancing postmenopausal osteoporosis: A study of KLF2 transcription factor secretion and PI3K-Akt signaling pathway activation by PIK3CA in bone marrow mesenchymal stem cells","volume":"20","author":"Ma","year":"2024","journal-title":"Arch. Med. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1177\/15353702231191117","article-title":"Fluoride induces osteoblast autophagy by inhibiting the PI3K\/AKT\/mTOR signaling pathway in vivo and in vitro","volume":"248","author":"Yan","year":"2023","journal-title":"Exp. Biol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1186\/s13018-025-05670-x","article-title":"miR-374-5p inhibits osteogenesis by targeting PTEN\/PI3K\/AKT signaling pathway","volume":"20","author":"Long","year":"2025","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5081","DOI":"10.1007\/s11033-023-08404-6","article-title":"Betaine regulates adipogenic and osteogenic differentiation of hAD-MSCs","volume":"50","author":"Jing","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1266\/ggs.22-00068","article-title":"Time series clustering analysis of genes during osteogenic differentiation of human mesenchymal stem cells","volume":"97","author":"Li","year":"2022","journal-title":"Genes Genet. Syst."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"110668","DOI":"10.1016\/j.ygeno.2023.110668","article-title":"Multi-omics analysis of bone marrow mesenchymal stem cell differentiation differences in osteoporosis","volume":"115","author":"Feng","year":"2023","journal-title":"Genomics"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jmst.2022.07.016","article-title":"Biomimetic hydroxyapatite coating on the 3D-printed bioactive porous composite ceramic scaffolds promoted osteogenic differentiation via PI3K\/AKT\/mTOR signaling pathways and facilitated bone regeneration in vivo","volume":"136","author":"Tan","year":"2023","journal-title":"J. Mater. Sci. Technol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Gong, C., Yang, J., Zhang, X., Wang, X., Wei, Z., Huang, X., and Guo, W. (2024). Surface functionalization of calcium magnesium phosphate cements with alginate sodium for enhanced bone regeneration via TRPM7\/PI3K\/Akt signaling pathway. Int. J. Biol. Macromol., 266.","DOI":"10.1016\/j.ijbiomac.2024.130998"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Yang, H., Zhang, F., Sun, S., Li, H., Li, L., Xu, H., Wang, J., Shao, M., Li, C., and Wang, H. (2023). Brushite-coated Mg-Nd-Zn-Zr alloy promotes the osteogenesis of vertebral laminae through IGF2\/PI3K\/AKT signaling pathway. Biomater. Adv., 152.","DOI":"10.1016\/j.bioadv.2023.213505"}],"updated-by":[{"DOI":"10.3390\/bioengineering12121375","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:00:00Z","timestamp":1748649600000}}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/6\/599\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:57:14Z","timestamp":1766051834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/12\/6\/599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,31]]},"references-count":80,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["bioengineering12060599"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering12060599","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,31]]}}}