10.61186/jcc.6.4.3 1 Review of bredigite-based 3D-printed bone scaffolds in biomedical applications 1 The use of three-dimensional (3D) bio-scaffolds for bone regeneration has gained significant attention due to the increasing demand for effective bone graft substitutes. Among various bioceramics, bredigite (Ca₇MgSi₄O₁₆) has emerged as a promising candidate due to its excellent bioactivity, suitable mechanical properties, and controlled biodegradability. Recent advancements in 3D printing technologies have enabled the fabrication of porous bredigite-based scaffolds with tunable structural and biological characteristics, facilitating improved cell adhesion, proliferation, and osteogenic differentiation. This review provides a comprehensive analysis of the latest developments in bredigite-based 3D-printed scaffolds, focusing on their fabrication techniques, mechanical behavior, and potential biomedical applications. Additionally, the key future directions for optimizing these scaffolds are discussed 1 13 Fatemeh Sharifjafari School of Science and Health, The University of Georgia, Tbilisi. Georgia info@jourcc.com Aramis Moradii Zand Institute of Higher Education, Shiraz, Fars Iran info@jourcc.com Reyhaneh Nasr Azadani Department of Biomaterials and Tissue Engineering, School of Advanced Technologies in Medicine, Isfahan University of MedicalSciences, Isfahan Iran info@jourcc.com Sana Radmehr School of Science and Health, The University of Georgia, Tbilisi. Georgia info@jourcc.com Saeid Gholizadeh Department of Pharmaceutical Chemistry, School of Science and Technology, The University of Georgia, Tbilisi Georgia info@jourcc.com Aida Mahdian Faculty of Medicine, Kashan University of Medical Sciences, Kashan Iran info@jourcc.com Bredigite 3D-printed Bone scaffolds Biomedical application Article.pdf [1] G. Fernandez de Grado, L. Keller, Y. Idoux-Gillet, Q. Wagner, A.-M. Musset, N. Benkirane-Jessel, F. Bornert, D. Offner, Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management, Journal of Tissue Engineering 9 (2018) 2041731418776819 .##[2] W. Schlickewei, C. Schlickewei, The use of bone substitutes in the treatment of bone defects–the clinical view and history, Macromolecular symposia, Wiley Online Library, 2007, pp. 10-23.##[3] A. Shirbacheh, K. Shirbache, PMMA Bone Cement: Properties, Applications, and Innovations, Journal of Composites and Compounds 5(17) (2023) .##[4] S. Bose, M. Roy, A. Bandyopadhyay, Recent advances in bone tissue engineering scaffolds, Trends Biotechnol 30(10) (2012) 546-54.##[5] S.S. Lee, X. Du, I. Kim, S.J. Ferguson, Scaffolds for bone-tissue engineering, Matter 5(9) (2022) 2722-2759.##[6] S. Bose, M. Roy, A. Bandyopadhyay, Recent advances in bone tissue engineering scaffolds, Trends in Biotechnology 30(10) (2012) 546-554 .##[7] Y. Khan, M.J. Yaszemski, A.G. Mikos, C.T. Laurencin, Tissue engineering of bone: material and matrix considerations, Jbjs 90(Supplement_1) (2008) 36-42 .##[8] D.F. Williams, On the mechanisms of biocompatibility, Biomaterials 29(20) (2008) 2941-2953 .##[9] M. Chen, Y. Li, W.-X. Hou, D.-Y. Peng, J.-K. Li, H.-X. Zhang, The antibacterial effect, biocompatibility, and osteogenesis of vancomycin-nanodiamond composite scaffold for infected bone defects, International Journal of Nanomedicine (2023) 1365-1380.##[10] M.J. Olszta, X. Cheng, S.S. Jee, R. Kumar, Y.-Y. Kim, M.J. Kaufman, E.P. Douglas, L.B. Gower, Bone structure and formation: A new perspective, Materials Science and Engineering: R: Reports 58(3-5) (2007) 77-116 .##[11] P. Lichte, H. Pape, T. Pufe, P. Kobbe, H. Fischer, Scaffolds for bone healing: concepts, materials and evidence, Injury 42(6) (2011) 569-573 .##[12] Q. Zhang, J. Zhou, P. Zhi, L. Liu, C. Liu, A. Fang, Q. Zhang, 3D printing method for bone tissue engineering scaffold, Medicine in Novel Technology and Devices 17 (2023) 100205.##[13] C. Wu, J. Chang, Synthesis and in vitro bioactivity of bredigite powders, Journal of biomaterials applications 21(3) (2007) 251-263 .##[14] M. Eilbagi, R. Emadi, K. Raeissi, M. Kharaziha, A. Valiani, Mechanical and cytotoxicity evaluation of nanostructured hydroxyapatite-bredigite scaffolds for bone regeneration, Materials Science and Engineering: C 68 (2016) 603-612 .##[15] C. Wu, J. Chang, J. Wang, S. Ni, W. Zhai, Preparation and characteristics of a calcium magnesium silicate (bredigite) bioactive ceramic, Biomaterials 26(16) (2005) 2925-2931 .##[16] D. Yi, C. Wu, B. Ma, H. Ji, X. Zheng, J. Chang, Bioactive bredigite coating with improved bonding strength, rapid apatite mineralization and excellent cytocompatibility, Journal of biomaterials applications 28(9) (2014) 1343-1353 .##[17] Q. Gao, J.S. Lee, B.S. Kim, G. Gao, Three-dimensional printing of smart constructs using stimuli-responsive biomaterials: A future direction of precision medicine, Int J Bioprint 9(1) (2023) 638.##[18] Y. Xuan, Y. Guo, L. Li, Yuzhang, C. Zhang, RuiJin, X. Yin, Z. Zhang, 3D-printed bredigite scaffolds with ordered arrangement structures promote bone regeneration by inducing macrophage polarization in onlay grafts, Journal of Nanobiotechnology 22(1) (2024) 102 .##[19] Y. Xuan, L. Li, C. Zhang, M. Zhang, J. Cao, Z. Zhang, The 3D-printed ordered bredigite scaffold promotes pro-healing of critical-sized bone defects by regulating macrophage polarization, International Journal of Nanomedicine (2023) 917-932.##[20] A. Dussault, A.A. Pitaru, M.H. Weber, L. Haglund, D.H. Rosenzweig, I. Villemure, Optimizing design parameters of PLA 3D-printed scaffolds for bone defect repair, Surgeries 3(3) (2022) 162-174 .##[21] X. Sun, Y. Mao, B. Liu, K. Gu, H. Liu, W. Du, R. Li, J. Zhang, Mesenchymal stem cell-derived exosomes enhance 3D-printed scaffold functions and promote alveolar bone defect repair by enhancing angiogenesis, Journal of Personalized Medicine 13(2) (2023) 180 .##[22] M. Khodaei, A. Nadi, Bredigite bioceramic: A promising candidate for bone tissue engineering, Silicon 16(13) (2024) 5213-5230.##[23] M. Kouhi, M. Shamanian, M. Fathi, A. Samadikuchaksaraei, A. Mehdipour, Synthesis, characterization, in vitro bioactivity and biocompatibility evaluation of hydroxyapatite/bredigite (Ca 7 MgSi 4 O 16) composite nanoparticles, Jom 68 (2016) 1061-1070 .##[24] C. Wu, J. Chang, Degradation, bioactivity, and cytocompatibility of diopside, akermanite, and bredigite ceramics, Journal of Biomedical Materials Research Part B: Applied Biomaterials: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials 83(1) (2007) 153-160 .##[25] Y. Xuan, L. Li, C. Zhang, M. Zhang, J. Cao, Z. Zhang, The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization, Int J Nanomedicine 18 (2023) 917-932 .##[26] Y. Feng, S. Zhu, D. Mei, J. Li, J. Zhang, S. Yang, S. Guan, Application of 3D printing technology in bone tissue engineering: a review, Current Drug Delivery 18(7) (2021) 847-861 .##[27] R.C.d.A.G. Mota, E.O. da Silva, F.F. de Lima, L.R. de Menezes, A.C.S. Thiele, 3D printed scaffolds as a new perspective for bone tissue regeneration: literature review, Materials Sciences and Applications 7(8) (2016) 430-452.##[28] S.Y. Chin, V. Dikshit, B. Meera Priyadarshini, Y. Zhang, Powder-Based 3D Printing for the Fabrication of Device with Micro and Mesoscale Features, Micromachines, 2020.##[29] A. Becerro, B. Pardal-Peláez, N. Quispe-López, J.-F. Blanco, C. Gómez-Polo, Main 3D Manufacturing Techniques for Customized Bone Substitutes. A Systematic Review, Materials 14(10) (2021) 2524 .##[30] J. Montero, A. Becerro, B. Pardal-Peláez, N. Quispe-López, J.-F. Blanco, C. Gómez-Polo, Main 3D manufacturing techniques for customized bone substitutes. A systematic review, Materials 14(10) (2021) 2524 .##[31] S.C. Daminabo, S. Goel, S.A. Grammatikos, H.Y. Nezhad, V.K. Thakur, Fused deposition modeling-based additive manufacturing (3D printing): techniques for polymer material systems, Materials Today Chemistry 16 (2020) 100248 .##[32] J. Jensen, J.H.D. Rölfing, D.Q. Svend Le, A.A. Kristiansen, J.V. Nygaard, L.B. Hokland, M. Bendtsen, M. Kassem, H. Lysdahl, C.E. Bünger, Surface‐modified functionalized polycaprolactone scaffolds for bone repair: In vitro and in vivo experiments, Journal of biomedical materials research Part A 102(9) (2014) 2993-3003 .##[33] I.J. Solomon, P. Sevvel, J. Gunasekaran, A review on the various processing parameters in FDM, Materials Today: Proceedings 37 (2021) 509-514 .##[34] G. Chen, C. Dong, L. Yang, Y. Lv, 3D Scaffolds with Different Stiffness but the Same Microstructure for Bone Tissue Engineering, ACS Appl Mater Interfaces 7(29) (2015) 15790-802 .##[35] L. Liulan, R. Bin, H. Qingxi, F. Minglun, Microstructural comparison and analysis of bone scaffold prepared by FDM and SLS process, World Congress on Medical Physics and Biomedical Engineering, September 7-12, 2009, Munich, Germany: Vol. 25/10 Biomaterials, Cellular and Tussue Engineering, Artificial Organs, Springer, 2010, pp. 109-112.##[36] J.M. Williams, A. Adewunmi, R.M. Schek, C.L. Flanagan, P.H. Krebsbach, S.E. Feinberg, S.J. Hollister, S. Das, Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering, Biomaterials 26(23) (2005) 4817-4827 .##[37] A. Mazzoli, C. Ferretti, A. Gigante, E. Salvolini, M. Mattioli-Belmonte, Selective laser sintering manufacturing of polycaprolactone bone scaffolds for applications in bone tissue engineering, Rapid prototyping journal 21(4) (2015) 386-392 .##[38] P. Fiedor, J. Ortyl, A New Approach to Micromachining: High-Precision and Innovative Additive Manufacturing Solutions Based on Photopolymerization Technology, Materials, 2020.##[39] S. Tarafder, V.K. Balla, N.M. Davies, A. Bandyopadhyay, S. Bose, Microwave‐sintered 3D printed tricalcium phosphate scaffolds for bone tissue engineering, Journal of tissue engineering and regenerative medicine 7(8) (2013) 631-641 .##[40] B.V. Nolens, M.-C. De Pauw, F. Lambert, In vitro and in vivo biocompatibility of calcium-phosphate scaffolds 3D printed by stereolithography for bone regeneration, (2019).##[41] J. Lv, P. Xiu, J. Tan, Z. Jia, H. Cai, Z. Liu, Enhanced angiogenesis and osteogenesis in critical bone defects by the controlled release of BMP-2 and VEGF: implantation of electron beam melting-fabricated porous Ti6Al4V scaffolds incorporating growth factor-doped fibrin glue, Biomedical materials 10(3) (2015) 035013.##[42] Y. Zhang, L. Zhang, R. Sun, Y. Jia, X. Chen, Y. Liu, H. Oyang, L. Feng, A new 3D printed titanium metal trabecular bone reconstruction system for early osteonecrosis of the femoral head, Medicine 97(26) (2018) e11088.##[43] A. Palmquist, A. Snis, L. Emanuelsson, M. Browne, P. Thomsen, Long-term biocompatibility and osseointegration of electron beam melted, free-form–fabricated solid and porous titanium alloy: Experimental studies in sheep, Journal of biomaterials applications 27(8) (2013) 1003-1016.##[44] C. Wu, J. Chang, W. Zhai, S. Ni, A novel bioactive porous bredigite (Ca 7 MgSi 4 O 16) scaffold with biomimetic apatite layer for bone tissue engineering, Journal of Materials Science: Materials in Medicine 18 (2007) 857-864 .##[45] M. Rahmati, M. Fathi, M. Ahmadian, Preparation and structural characterization of bioactive bredigite (Ca7MgSi4O16) nanopowder, Journal of Alloys and Compounds 732 (2018) 9-15.##[46] Q. Fu, E. Saiz, M.N. Rahaman, A.P. Tomsia, Bioactive glass scaffolds for bone tissue engineering: state of the art and future perspectives, Materials science and engineering: C 31(7) (2011) 1245-1256 .##[47] H. Ghomi, R. Emadi, Fabrication of bioactive porous bredigite (Ca7MgSi4O16) scaffold via space holder method, International Journal of Materials Research 109(3) (2018) 257-264.##[48] M. Kouhi, M. Fathi, V.J. Reddy, S. Ramakrishna, Bredigite reinforced electrospun nanofibers for bone tissue engineering, Materials Today: Proceedings 7 (2019) 449-454 .##[49] T.D. Ngo, A. Kashani, G. Imbalzano, K.T. Nguyen, D. Hui, Additive manufacturing (3D printing): A review of materials, methods, applications and challenges, Composites Part B: Engineering 143 (2018) 172-196 .##[50] D. Liu, X. Zhou, F. Wang, Y. Feng, Y. Shi, Research and analysis of the properties of bredigite-based 3D-printed bone scaffolds, International Journal of Bioprinting 9(3) (2023) 708.##[51] C. Qin, D. Che, D. Liu, Z. Zhang, Y. Feng, Preparation and characterization of different micro/nano structures on the surface of bredigite scaffolds, Scientific Reports 13(1) (2023) 9072 .##[52] H. Zhang, Z. Zhao, C. Wu, Bioactive Inorganic Materials for Innervated Multi‐Tissue Regeneration, Advanced Science (2025) 2415344 .##[53] A. Khandan, N. Ozada, S. Saber-Samandari, M.G. Nejad, On the mechanical and biological properties of bredigite-magnetite (Ca7MgSi4O16-Fe3O4) nanocomposite scaffolds, Ceramics International 44(3) (2018) 3141-3148 .##[54] M.F. Ulum, A.K. Nasution, A.H. Yusop, A. Arafat, M.R.A. Kadir, V. Juniantito, D. Noviana, H. Hermawan, Evidences of in vivo bioactivity of Fe‐bioceramic composites for temporary bone implants, Journal of Biomedical Materials Research Part B: Applied Biomaterials 103(7) (2015) 1354-1365 .##[55] T. Huang, J. Cheng, Y. Zheng, In vitro degradation and biocompatibility of Fe–Pd and Fe–Pt composites fabricated by spark plasma sintering, Materials Science and Engineering: C 35 (2014) 43-53 .##[56] C. Gao, M. Yao, S. Li, P. Feng, S. Peng, C. Shuai, Highly biodegradable and bioactive Fe-Pd-bredigite biocomposites prepared by selective laser melting, Journal of advanced research 20 (2019) 91-104 .##[57] F.M. Nakhaee, M. Rajabi, H.R. Bakhsheshi-Rad, In-vitro assessment of β-tricalcium phosphate/bredigite-ciprofloxacin (CPFX) scaffolds for bone treatment applications, Biomedical Materials 16(4) (2021) 045038 .##[58] R. Rezaie Shahraki, H. Ghomi, Enhancing Bone Tissue Regeneration: Investigating the Role of Bredigite in Improving Osteoconductive Properties of Gelatin/Polylactic Acid Scaffolds, Polymers for Advanced Technologies 36(1) (2025) e70076 .##[59] S. Ghasemi, H. Ghomi, Investigation of applying chitosan coating on antibacterial and biocompatibility properties of bredigite/titanium dioxide composite scaffolds, Journal of Biomaterials Applications 36(3) (2021) 406-418 .##[60] J. Yang, Z. Zhan, X. Li, M. Hu, Y. Zhu, Y. Xiao, X. Xu, Fullerol-reinforced antioxidantive 3D-printed bredigite scaffold for accelerating bone healing, Materials Today Bio 27 (2024) 101120 .##[61] S. Askari, E. Yazdani, L. Arabuli, H. Goldadi, S.A. Shahidi Marnani, M. Emami, In-vitro and in-vivo examination for bioceramics degradation, Journal of Composites and Compounds 4(12) (2022) 169-177.##[62] D. Liu, X. Zhou, F. Wang, Y. Feng, Y. Shi, Research and analysis of the properties of bredigite-based 3D-printed bone scaffolds, IJB 9(3) (2023) .13F.Sharif Jafariet al /Journal of Composites and Compounds 6 (2024) 1-13.##[63] E. García-Gareta, M.J. Coathup, G.W. Blunn, Osteoinduction of bone grafting materials for bone repair and regeneration, Bone 81 (2015) 112-121.##[64] A. Shahbaz, N. Tajbakhsh, A. Doroudi, F. Bakhshi, S. Ranjbar, Bredigite-containing materials for regenerative medicine applications: A rapid review, Journal of Composites and Compounds 5(16) (2023) 190-199.##[65] I.-H. Jo, K.-H. Shin, Y.-M. Soon, Y.-H. Koh, J.-H. Lee, H.-E. Kim, Highly porous hydroxyapatite scaffolds with elongated pores using stretched polymeric sponges as novel template, Materials Letters 63(20) (2009) 1702-1704 .[66] A. Nauth, E. Schemitsch, B. Norris, Z. Nollin, J.T. Watson, Critical-Size Bone Defects: Is There a Consensus for Diagnosis and Treatment?, Journal of Orthopaedic Trauma 32 (2018).##[67] H. Bakhsheshi-Rad, E. Hamzah, N. Abbasizadeh, A. Najafinezhad, M. Kashefian, Synthesis of novel nanostructured bredigite–amoxicillin scaffolds for bone defect treatment: cytocompatibility and antibacterial activity, Journal of Sol-Gel Science and Technology 86 (2018) 83-93 .##[68] T. Sopcak, L. Medvecky, P. Jevinova, M. Giretova, A. Mahun, L. Kobera, R. Stulajterova, F. Kromka, V. Girman, M. Balaz, Physico-chemical, mechanical and antibacterial properties of the boron modified biphasic larnite/bredigite cements for potential use in dentistry, Ceramics International 49(4) (2023) 6531-6544 .##[69] Y. Xuan, L. Lin, Z. Chenping, Z. Min, C. Junkai, Z. and Zhang, The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization, International Journal of Nanomedicine 18(null) (2023) 917-932 .##[70] R. Keihan, A. Ghorbani, E. Salahinejad, E. Sharifi, L. Tayebi, Biomineralization, strength and cytocompatibility improvement of bredigite scaffolds through doping/coating, Ceramics International 46(13) (2020) 21056-21063 .##[71] L. Chen, L. Liu, C. Wu, R. Yang, J. Chang, X. Wei, The extracts of bredigite bioceramics enhanced the pluripotency of human dental pulp cells, Journal of Biomedical Materials Research Part A 105(12) (2017) 3465-3474.