{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:42:27Z","timestamp":1792791747531,"version":"4.5.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Mandibular defects pose significant challenges in reconstructive surgery, and scaffold materials are increasingly recognized for their potential to address these challenges. Among various scaffold materials, Beta-tricalcium phosphate (\u03b2-TCP) is noted for its exceptional osteogenic properties. However, improvements in its biodegradation rate and mechanical strength are essential for optimal performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we developed a novel \u03b2-TCP-based scaffold, CFBB, by calcining fetal bovine cancellous bone. To enhance its properties, we modified CFBB with Chitosan (CS) and Zinc (Zn), creating three additional scaffold materials: CFBB\/CS, CFBB\/Zn<jats:sup>2+<\/jats:sup>, and CFBB\/Zn<jats:sup>2+<\/jats:sup>\/CS. We conducted comprehensive assessments of their physicochemical and morphological properties, degradation rates, biocompatibility, osteogenic ability, new bone formation, and neovascularization both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings revealed that all four materials were biocompatible and safe for use. The modifications with CS and Zn<jats:sup>2+<\/jats:sup> significantly improved the mechanical strength, osteogenic, and angiogenic properties of CFBB, while concurrently decelerating its resorption rate. Among the tested materials, CFBB\/Zn<jats:sup>2+<\/jats:sup>\/CS demonstrated superior performance in promoting bone regeneration and vascularization, making it a particularly promising candidate for mandibular reconstruction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The CFBB\/Zn<jats:sup>2+<\/jats:sup>\/CS scaffold material, with its enhanced mechanical, osteogenic, and angiogenic properties, and a controlled resorption rate, emerges as a highly effective alternative for the repair of oral mandible defects. This study underscores the potential of combining multiple bioactive agents in scaffold materials to improve their functionality for specific clinical applications in bone tissue engineering.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbioe.2024.1355493","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T11:05:08Z","timestamp":1727694308000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Zinc and chitosan-enhanced \u03b2-tricalcium phosphate from calcined fetal bovine bone for mandible reconstruction"],"prefix":"10.3389","volume":"12","author":[{"given":"Jianye","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shennan","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3991","DOI":"10.1016\/j.biomaterials.2003.10.086","article-title":"Microcellular PolyHIPE polymer supports osteoblast growth and bone formation in vitro","volume":"25","author":"Akay","year":"2004","journal-title":"Biomaterials"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1002\/bab.2065","article-title":"Structural and chemical features of xenograft bone substitutes: a systematic review of in vitro studies","volume":"68","author":"Amid","year":"2021","journal-title":"Biotechnol. Appl. Biochem."},{"key":"B3","volume-title":"Astm F756-17: standard practice for assessment of hemolytic properties of materials","year":"2017"},{"key":"B4","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s10856-013-5062-7","article-title":"Mechanical properties and in vitro cellular behavior of zinc-containing nano-bioactive glass doped biphasic calcium phosphate bone substitutes","volume":"25","author":"Bad","year":"2014","journal-title":"J. Mater Sci. Mater Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.msec.2005.11.004","article-title":"Influence of ZnO doping in calcium phosphate ceramics","volume":"27","author":"Bandyopadhyay","year":"2007","journal-title":"Mater. Sci. Eng. C"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3026","DOI":"10.1002\/jbm.a.35438","article-title":"Osteoblast biocompatibility of novel chitosan crosslinker, hexamethylene-1,6-diaminocarboxysulfonate","volume":"103","author":"Beringer","year":"2015","journal-title":"J. Biomed. Mater Res. A"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/9365747","article-title":"Function, structure, and transport aspects of ZIP and ZnT zinc transporters in immune cells","volume":"2018","author":"Bin","year":"2018","journal-title":"J. Immunol. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.mattod.2017.02.002","article-title":"Characterization and distribution of mechanically competent mineralized tissue in micropores of \u03b2-tricalcium phosphate bone substitutes","volume":"20","author":"Bohner","year":"2017","journal-title":"Mater. Today"},{"key":"B9","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.actbio.2020.06.022","article-title":"\u03b2-tricalcium phosphate for bone substitution: synthesis and properties","volume":"113","author":"Bohner","year":"2020","journal-title":"Acta Biomater."},{"key":"B10","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/jbm.b.31807","article-title":"Increasing strut porosity in silicate-substituted calcium-phosphate bone graft substitutes enhances osteogenesis","volume":"97","author":"Campion","year":"2011","journal-title":"J. Biomed. Mater Res. B Appl. Biomater."},{"key":"B11","doi-asserted-by":"publisher","first-page":"101433","DOI":"10.1016\/j.apmt.2022.101433","article-title":"Bioadaptable bone regeneration of Zn-containing silicocarnotite bioceramics with moderate biodegradation and antibacterial activity","volume":"27","author":"Deng","year":"2022","journal-title":"Appl. Mater Today"},{"key":"B12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jhazmat.2006.11.061","article-title":"Mechanisms and kinetics of chelating reaction between novel chitosan derivatives and Zn(II)","volume":"146","author":"Ding","year":"2007","journal-title":"J. Hazard Mater"},{"key":"B13","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1111\/cid.12599","article-title":"In vivo evaluation of \u03b2\u2010CS\/n\u2010HA with different physical properties as a new bone graft material","volume":"20","author":"Elkholy","year":"2018","journal-title":"Clin. Implant Dent. Relat. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"650598","DOI":"10.3389\/fbioe.2021.650598","article-title":"Chitosan-based functional materials for skin wound repair: mechanisms and applications","volume":"9","author":"Feng","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e87755","DOI":"10.1371\/journal.pone.0087755","article-title":"Characterization of mechanical and biological properties of 3-D scaffolds reinforced with zinc oxide for bone tissue engineering","volume":"9","author":"Feng","year":"2014","journal-title":"PLoS One"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1177\/1081286520978516","article-title":"In-depth gaze at the astonishing mechanical behavior of bone: a review for designing bio-inspired hierarchical metamaterials","volume":"26","author":"Giorgio","year":"2021","journal-title":"Math. Mech. Solids"},{"key":"B17","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/jbm.a.10593","article-title":"Resorption patterns of calcium-phosphate cements in bone","volume":"66","author":"Gisep","year":"2003","journal-title":"J. Biomed. Mater Res. A"},{"key":"B18","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.jnutbio.2009.01.002","article-title":"Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation, matrix maturation, and mineralization in the long bones of growing rats","volume":"21","author":"Hadley","year":"2010","journal-title":"J. Nutr. Biochem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"106888","DOI":"10.1016\/j.jece.2021.106888","article-title":"Wound healing efficacy of biocompatible hydroxyapatite from bovine bone waste for bone tissue engineering application","volume":"10","author":"Han","year":"2022","journal-title":"J. Environ. Chem. Eng."},{"key":"B20","doi-asserted-by":"publisher","first-page":"S22","DOI":"10.1016\/j.injury.2011.06.008","article-title":"Porosity and mechanical strength of bone substitutes: what is optimal for bone regeneration?","volume":"42","author":"Hannink","year":"2011","journal-title":"Injury"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5014","DOI":"10.1016\/j.biomaterials.2006.05.039","article-title":"Effect of silicon level on rate, quality and progression of bone healing within silicate-substituted porous hydroxyapatite scaffolds","volume":"27","author":"Hing","year":"2006","journal-title":"Biomaterials"},{"key":"B22","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.spinee.2006.07.017","article-title":"Comparative performance of three ceramic bone graft substitutes","volume":"7","author":"Hing","year":"2007","journal-title":"Spine J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"9622","DOI":"10.1016\/j.biomaterials.2011.09.009","article-title":"Biomimetic nanofibrous scaffolds for bone tissue engineering","volume":"32","author":"Holzwarth","year":"2011","journal-title":"Biomaterials"},{"key":"B24","doi-asserted-by":"publisher","first-page":"101559","DOI":"10.1016\/j.jscs.2022.101559","article-title":"Crystallographic dependency of waste cow bone, hydroxyapatite, and \u03b2-tricalcium phosphate for biomedical application","volume":"26","author":"Hossain","year":"2022","journal-title":"J. Saudi Chem. Soc."},{"key":"B25","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1088\/1748-6041\/1\/3\/007","article-title":"Dissolution rate of zinc-containing \u03b2-tricalcium phosphate ceramics","volume":"1","author":"Ito","year":"2006","journal-title":"Biomed. Mater."},{"key":"B26","doi-asserted-by":"publisher","first-page":"475","DOI":"10.13701\/j.cnki.kqyxyj.2017.05.003","article-title":"Preparation, Characterization and cytocompatibility of calcined bone Blocks from adult and fetal cattle","volume":"33","author":"Jianye","year":"2017","journal-title":"J. Stomatology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"15725","DOI":"10.1016\/j.ceramint.2020.03.192","article-title":"A review of bioceramic porous scaffolds for hard tissue applications: effects of structural features","volume":"46","author":"Jodati","year":"2020","journal-title":"Ceram. Int."},{"key":"B28","doi-asserted-by":"publisher","first-page":"5474","DOI":"10.1016\/j.biomaterials.2005.02.002","article-title":"Porosity of 3D biomaterial scaffolds and osteogenesis","volume":"26","author":"Karageorgiou","year":"2005","journal-title":"Biomaterials"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e10845","DOI":"10.1016\/j.heliyon.2022.e10845","article-title":"Intermittent compressive force regulates human periodontal ligament cell behavior via yes-associated protein","volume":"8","author":"Klincumhom","year":"2022","journal-title":"Heliyon"},{"key":"B30","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.ijfoodmicro.2010.09.012","article-title":"Antimicrobial properties of chitosan and mode of action: a state of the art review","volume":"144","author":"Kong","year":"2010","journal-title":"Int. J. Food Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1080\/03008200290001104","article-title":"Geometry of artificial ECM: sizes of pores controlling phenotype expression in BMP-induced osteogenesis and chondrogenesis","volume":"43","author":"Kuboki","year":"2002","journal-title":"Connect. Tissue Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"105","DOI":"10.2106\/00004623-200100002-00005","article-title":"Geometry of carriers controlling phenotypic expression in BMP-induced osteogenesis and chondrogenesis","volume":"83","author":"Kuboki","year":"2001","journal-title":"J. Bone Jt. Surg. Am."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1134\/S1027451010010015","article-title":"Vacuum ultraviolet smoothing of nanometer-scale asperities of poly(methyl methacrylate) surface","volume":"4","author":"Lapshin","year":"2010","journal-title":"J. Surf. Investigation"},{"key":"B34","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.seppur.2004.08.002","article-title":"Copper adsorption on chitosan-cellulose hydrogel beads: behaviors and mechanisms","volume":"42","author":"Li","year":"2005","journal-title":"Sep. Purif. Technol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1007\/s12011-013-9683-y","article-title":"Effects of zinc transporter on differentiation of bone marrow mesenchymal stem cells to osteoblasts","volume":"154","author":"Liu","year":"2013","journal-title":"Biol. Trace Elem. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"115736","DOI":"10.1016\/j.bone.2020.115736","article-title":"Do polyunsaturated fatty acids protect against bone loss in our aging and osteoporotic population?","volume":"143","author":"Martyniak","year":"2021","journal-title":"Bone"},{"key":"B37","doi-asserted-by":"publisher","first-page":"4186","DOI":"10.3390\/polym14194186","article-title":"Hydrogel: a potential material for bone tissue engineering repairing the segmental mandibular defect","volume":"14","author":"Maruf","year":"2022","journal-title":"Polymers"},{"key":"B38","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1080\/00914037.2022.2052729","article-title":"Current and future perspectives on biomaterials for segmental mandibular defect repair","volume":"72","author":"Maruf","year":"2023","journal-title":"Int. J. Polym. Mater. Polym. Biomaterials"},{"key":"B39","doi-asserted-by":"publisher","first-page":"104993","DOI":"10.1016\/J.MTCOMM.2022.104993","article-title":"Preparation and properties of porous biphasic calcium phosphate\/bioactive glass composite scaffolds for biomedical applications","volume":"33","author":"Monmaturapoj","year":"2022","journal-title":"Mater Today Commun."},{"key":"B40","doi-asserted-by":"publisher","first-page":"9806","DOI":"10.1038\/srep09806","article-title":"In vitro study of surface modified poly(ethylene glycol)-impregnated sintered bovine bone scaffolds on human fibroblast cells","volume":"5","author":"Pramanik","year":"2015","journal-title":"Sci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1039\/c2bm00012a","article-title":"Effects of zinc and strontium substitution in tricalcium phosphate on osteoclast differentiation and resorption","volume":"1","author":"Roy","year":"2013","journal-title":"Biomater. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.ijbiomac.2016.01.112","article-title":"Chitosan based biocomposite scaffolds for bone tissue engineering","volume":"93","author":"Saravanan","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.ijbiomac.2011.04.010","article-title":"Preparation, characterization and antimicrobial activity of a bio-composite scaffold containing chitosan\/nano-hydroxyapatite\/nano-silver for bone tissue engineering","volume":"49","author":"Saravanan","year":"2011","journal-title":"Int. J. Biol. Macromol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.1021\/acs.biochem.1c00415","article-title":"Formation of the metal-binding core of the ZRT\/IRT-like protein (ZIP) family zinc transporter","volume":"60","author":"Sharma","year":"2021","journal-title":"Biochemistry"},{"key":"B45","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.ijbiomac.2019.04.107","article-title":"Design and evaluation of chitosan\/chondroitin sulfate\/nano-bioglass based composite scaffold for bone tissue engineering","volume":"133","author":"Singh","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"7828","DOI":"10.1016\/j.biomaterials.2014.05.087","article-title":"The potential role of free chitosan in bone trauma and bone cancer management","volume":"35","author":"Tan","year":"2014","journal-title":"Biomaterials"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1016\/j.ijbiomac.2020.10.019","article-title":"Enhanced antifungal activity of novel cationic chitosan derivative bearing triphenylphosphonium salt via azide-alkyne click reaction","volume":"165","author":"Tan","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1002\/jbm.a.32532","article-title":"In vivo evaluation of highly macroporous ceramic scaffolds for bone tissue engineering","volume":"93","author":"Teixeira","year":"2010","journal-title":"J. Biomed. Mater Res. A"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2252","DOI":"10.3390\/md8082252","article-title":"Chitosan composites for bone tissue engineering - an overview","volume":"8","author":"Venkatesan","year":"2010","journal-title":"Mar. Drugs"},{"key":"B50","doi-asserted-by":"publisher","first-page":"7117","DOI":"10.3390\/ma15207117","article-title":"Modulation of osteogenesis and angiogenesis activities based on ionic release from Zn\u2013Mg alloys","volume":"15","author":"Wang","year":"2022","journal-title":"Materials"},{"key":"B51","doi-asserted-by":"publisher","first-page":"111372","DOI":"10.1016\/j.matdes.2022.111372","article-title":"Marine plankton exoskeleton-derived honeycombed hydroxyapatite bone granule for bone tissue engineering","volume":"224","author":"Won","year":"2022","journal-title":"Mater Des."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/8168943","article-title":"The possible roles of biological bone constructed with peripheral blood derived EPCs and BMSCs in osteogenesis and angiogenesis","volume":"2016","author":"Wu","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2669","DOI":"10.1007\/s10856-008-3395-4","article-title":"Synthesis and characterization of tricalcium phosphate with Zn and Mg based dopants","volume":"19","author":"Xue","year":"2008","journal-title":"Mater. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/iej.12777","article-title":"Physicochemical properties and cytotoxicity of an experimental resin-based pulp capping material containing the quaternary ammonium salt and portland cement","volume":"51","author":"Yang","year":"2018","journal-title":"Int. Endod. J."},{"key":"B55","doi-asserted-by":"publisher","first-page":"112087","DOI":"10.1016\/j.msec.2021.112087","article-title":"Alginate\/chitosan modified immunomodulatory titanium implants for promoting osteogenesis in vitro and in vivo","volume":"124","author":"Yin","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"B56","doi-asserted-by":"publisher","first-page":"17860","DOI":"10.1039\/c8ra00383a","article-title":"Enhanced bioactivity and osteoinductivity of carboxymethyl chitosan\/nanohydroxyapatite\/graphene oxide nanocomposites","volume":"8","author":"Yu","year":"2018","journal-title":"RSC Adv."},{"key":"B57","doi-asserted-by":"publisher","first-page":"13614","DOI":"10.1073\/pnas.1003600107","article-title":"Osteoinductive ceramics as a synthetic alternative to autologous bone grafting","volume":"107","author":"Yuan","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B58","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.bbrc.2011.07.082","article-title":"In vitro prominent bone regeneration by release zinc ion from Zn-modified implant","volume":"412","author":"Yusa","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B59","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1039\/C4BM00291A","article-title":"Bone tissue regeneration: the role of scaffold geometry","volume":"3","author":"Zadpoor","year":"2015","journal-title":"Biomater. Sci."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2024.1355493\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T11:05:12Z","timestamp":1727694312000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2024.1355493\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":59,"alternative-id":["10.3389\/fbioe.2024.1355493"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2024.1355493","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,27]]},"article-number":"1355493"}}