1 Computational design of multifunctional bioactive glass nanoparticles: A multi-objective optimization approach to balance osteogenesis, anticancer activity, and antibacterial efficacy 1 Developing multifunctional biomaterials that can simultaneously support bone regeneration, suppress tumor growth, and prevent infection is still a major challenge in treating bone cancer. Naruphontjirakul et al. recently showed that bioactive glass nanoparticles co-doped with zinc and silver (Zn/Ag-BGNPs)-, specifically the 0.5Ag–1Zn and 1Ag–1Zn formulations-demonstrated encouraging triple functionality: osteogenic differentiation in hFOB 1.19 cells, selective cytotoxicity against MG-63 osteosarcoma cells, and broad-spectrum antibacterial properties while remaining non-toxic to hFOB 1.19 cells at a concentration of 125 µg/mL. The design of such materials has focused on empirical methods with little systematic consideration of the trade-offs between competing biological objectives. Therefore, in this study, we develop and implement an innovative data-driven multi-objective optimization framework that utilizes the entire experimental data set from the study noted above, to identify Pareto-optimal Ag/Zn compositions. By predicting an Ag-Zn effect that favored one composition over another, this study provides a rationale for the predictive design of multifunctional biomaterials—a study that demonstrates that high-performance therapeutic platforms can be optimized computationally without new experimentation, thereby increasing the speed for clinical translation to orthopedic applications in bone regeneration. 1 5 Michael Askari Department of Computer Engineering, Payame Noor University (PNU), Sari Branch Sari, Mazandaran Iran michaelaskari2002@gmail.com Lili Arabuli Department of Chemistry, School of Science and Technology, University of Georgia, Tbilisi 0171 Georgia l.arabuli@ug.edu.ge Bioactive glass nanoparticles (BGNPs) Zinc/silver co-doping Multi-objective optimization NSGA-II algorithm Bone tissue engineering Osteogenesis Antibacterial nanoparticles [1] L. Keil, Bone Tumors: Primary Bone Cancers, FP essentials 493 (2020) 22-26.##[2] R.W. Johnson, L.J. Suva, Hallmarks of bone metastasis, Calcified tissue international 102(2) (2018) 141-151.##[3] A.E. Bădilă, D.M. Rădulescu, A.-G. Niculescu, A.M. Grumezescu, M. Rădulescu, A.R. Rădulescu, Recent advances in the treatment of bone metastases and primary bone tumors: An up-to-date review, Cancers 13(16) (2021) 4229.##[4] M. Vallet‐Regí, D. Lozano, B. González, I. Izquierdo‐Barba, Biomaterials against bone infection, Advanced healthcare materials 9(13) (2020) 2000310.##[5] Y. Hui, X. Yi, F. Hou, D. Wibowo, F. Zhang, D. Zhao, H. Gao, C.-X. Zhao, Role of nanoparticle mechanical properties in cancer drug delivery, ACS nano 13(7) (2019) 7410-7424.##[6] F. Sharifjafari, D. Nejadkoorki, S. Bahadori, Biomedical applications of silica nanoparticle compounds, Journal of Composites and Compounds 6(20) (2024).##[7] Y. Lu, J. Zhang, Y. Chen, Y. Kang, Z. Liao, Y. He, C. Zhang, Novel immunotherapies for osteosarcoma, Frontiers in Oncology 12 (2022) 830546.##[8] S.K. Kapoor, R. Thiyam, Management of infection following reconstruction in bone tumors, Journal of clinical orthopaedics and trauma 6(4) (2015) 244-251.##[9] H. Wei, J. Cui, K. Lin, J. Xie, X. Wang, Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration, Bone research 10(1) (2022) 17.##[10] M. Yamaguchi, Role of nutritional zinc in the prevention of osteoporosis, Molecular and cellular biochemistry 338(1) (2010) 241-254.##[11] P. Thanasrisuebwong, J.R. Jones, S. Eiamboonsert, N. Ruangsawasdi, B. Jirajariyavej, P. Naruphontjirakul, Zinc-containing sol–gel glass nanoparticles to deliver therapeutic ions, Nanomaterials 12(10) (2022) 1691.##[12] K. Schuhladen, L. Stich, J. Schmidt, A. Steinkasserer, A.R. Boccaccini, E. Zinser, Cu, Zn doped borate bioactive glasses: antibacterial efficacy and dose-dependent in vitro modulation of murine dendritic cells, Biomaterials science 8(8) (2020) 2143-2155.##[13] C. Heras, J. Jiménez-Holguín, A. Doadrio, M. Vallet-Regí, S. Sánchez-Salcedo, A. Salinas, Multifunctional antibiotic-and zinc-containing mesoporous bioactive glass scaffolds to fight bone infection, Acta biomaterialia 114 (2020) 395-406.##[14] S. Chen, S. Greasley, Z. Ong, P. Naruphontjirakul, S. Page, J. Hanna, A. Redpath, O. Tsigkou, S. Rankin, M. Ryan, Biodegradable zinc-containing mesoporous silica nanoparticles for cancer therapy, Materials Today Advances 6 (2020) 100066.##[15] A.M. El-Kady, A.F. Ali, R.A. Rizk, M.M. Ahmed, Synthesis, characterization and microbiological response of silver doped bioactive glass nanoparticles, Ceramics International 38(1) (2012) 177-188.##[16] A. Balamurugan, G. Balossier, D. Laurent-Maquin, S. Pina, A. Rebelo, J. Faure, J. Ferreira, An in vitro biological and anti-bacterial study on a sol–gel derived silver-incorporated bioglass system, dental materials 24(10) (2008) 1343-1351.##[17] J.S. Fernandes, P. Gentile, R.A. Pires, R.L. Reis, P.V. Hatton, Multifunctional bioactive glass and glass-ceramic biomaterials with antibacterial properties for repair and regeneration of bone tissue, Acta biomaterialia 59 (2017) 2-11.##[18] A.A. El-Rashidy, G. Waly, A. Gad, A.A. Hashem, P. Balasubramanian, S. Kaya, A.R. Boccaccini, I. Sami, Preparation and in vitro characterization of silver-doped bioactive glass nanoparticles fabricated using a sol-gel process and modified Stöber method, Journal of Non-Crystalline Solids 483 (2018) 26-36.##[19] V.P.S. Sidhu, R. Borges, M. Yusuf, S. Mahmoudi, S.F. Ghorbani, M. Hosseinikia, P. Salahshour, F. Sadeghi, M. Arefian, A comprehensive review of bioactive glass: synthesis, ion substitution, application, challenges, and future perspectives, Journal of Composites and Compounds 3(9) (2021) 247-261.##[20] P. Naruphontjirakul, P. Kanchanadumkerng, P. Ruenraroengsak, Multifunctional Zn and Ag co-doped bioactive glass nanoparticles for bone therapeutic and regeneration, Scientific Reports 13(1) (2023) 6775.##[21] S. Kargozar, M. Montazerian, E. Fiume, F. Baino, Multiple and promising applications of strontium (Sr)-containing bioactive glasses in bone tissue engineering, Frontiers in bioengineering and biotechnology 7 (2019) 161.