1 Predictive drug release modeling of curcumin from Ag2O/SiO2-functionalized CS/PVA/SA hydrogels for enhanced wound healing 1 Chitosan/poly(vinyl alcohol)/sodium alginate (CS/PVA/SA) hydrogels have been established as a potential drug delivery vehicle for controlled drug release in wound healing applications when formulated with antimicrobial nanoparticles. In this research, we characterize the effect of particle loading (0–20 wt%) of mesoporous Ag2O/SiO2 nanoparticle addition on the curcumin drug release from CS/PVA/SA hydrogels. A first-order kinetic model was created to be able to predict drug release from CS/PVA/SA hydrogels with varying Ag2O/SiO2 NP composition fractions. The experimental results validated the model well (i.e., global RMSE = 0.0625), demonstrating that drug release is effectively slowed in a substantive manner depending on the nanoparticle loading added. Reliability of the system in the context of parametric uncertainty was evaluated through the use of Monte Carlo Simulations along with the kinetic model, where success probability was defined as the potential to achieve >80% cumulative drug release. Our results demonstrated a significant time-dependent increase in the success probability (R2 = 0.9822) toward nearly complete certainty after 20 hours, while nanoparticle loading exhibited an inverse relationship on drug release efficiency (R2 = 1), with the best drug release efficiency occurring at loading below 10wt%. Results offer a way to predictively design nanocomposite hydrogels for personalized drug release applications. 1 5 Kamran Shirbache Hôpital Robert Debré, Groupe Hospitalier Universitaire AP-HP Nord-Université Paris-Cité France Kamranshirbache@gmail.com Ali Shirbacheh Urgences de centre hospitalier de l'agglomération de Nevers France shirbacheh.a@ght58.fr Monte Carlo simulation Modeling Drug release behavior SiO2 Nanoparticle Ag2O Nanoparticle Wound healing [1] Y. Yang, H. Chen, X. Zou, X.-L. Shi, W.-D. Liu, L. Feng, G. Suo, X. Hou, X. Ye, L. Zhang, Flexible carbon-fiber/semimetal Bi nanosheet arrays as separable and recyclable plasmonic photocatalysts and photoelectrocatalysts, ACS applied materials and interfaces 12(22) (2020) 24845-24854.##[2] J. Guo, J. Gao, C. Xiao, L. Chen, L. Qian, Mechanochemical reactions of GaN-Al2O3 interface at the nanoasperity contact: Roles of crystallographic polarity and ambient humidity, Friction 10(7) (2022) 1005-1018.##[3] N. Gao, X. Guo, J. Deng, B. Cheng, H. Hou, Elastic wave modulation of double-leaf ABH beam embedded mass oscillator, Applied Acoustics 173 (2021) 107694.##[4] X. Zhu, F. Lin, Z. Zhang, X. Chen, H. Huang, D. Wang, J. Tang, X. Fang, D. Fang, J.C. Ho, Enhancing performance of a GaAs/AlGaAs/GaAs nanowire photodetector based on the two-dimensional electron–hole tube structure, Nano letters 20(4) (2020) 2654-2659.##[5] H. Zheng, B. Zuo, Functional silk fibroin hydrogels: preparation, properties and applications, Journal of Materials Chemistry B 9(5) (2021) 1238-1258.##[6] A.N. Tahneh, B. Dashtipour, A. Ghofrani, S.K. Nejad, Crosslinked natural hydrogels for drug delivery systems, Journal of Composites and Compounds 4(11) (2022) 109-123.##[7] X. Zhang, Y. Zhang, Heat transfer and flow characteristics of Fe3O4-water nanofluids under magnetic excitation, International Journal of Thermal Sciences 163 (2021) 106826.##[8] S. Mondal, S. Das, A.K. Nandi, A review on recent advances in polymer and peptide hydrogels, Soft Matter 16(6) (2020) 1404-1454.##[9] Y. Li, X. Ren, T. Zhao, D. Xiao, K. Liu, D. Fang, Dynamic response of stiffened plate under internal blast: Experimental and numerical investigation, Marine structures 77 (2021) 102957.##[10] N.B. Hoveizavi, F. Alihosseini, S. Lehner, P. Meier, S. Gaan, Colorimetric pH-responsive nanofibrous hydrogels for in vitro monitoring of wound infection, Journal of Materials Chemistry B (2025).##[11] T.S. Welles, J. Ahn, Investigation of the effects of electrochemical reactions on complex metal tribocorrosion within the human body, Heliyon 7(5) (2021).##[12] V. Kanikireddy, K. Varaprasad, T. Jayaramudu, C. Karthikeyan, R. Sadiku, Carboxymethyl cellulose-based materials for infection control and wound healing: A review, International Journal of Biological Macromolecules 164 (2020) 963-975.##[13] Y. Guo, S. Pan, F. Jiang, E. Wang, L. Miinea, N. Marchant, M. Cakmak, Anisotropic swelling wound dressings with vertically aligned water absorptive particles, RSC advances 8(15) (2018) 8173-8180.##[14] H.J. Choi, T. Thambi, Y.H. Yang, S.I. Bang, B.S. Kim, D.G. Pyun, D.S. Lee, AgNP and rhEGF-incorporating synergistic polyurethane foam as a dressing material for scar-free healing of diabetic wounds, RSC advances 7(23) (2017) 13714-13725.##[15] B.D. Texier, A. Ibarra, F. Melo, Optimal propulsion of an undulating slender body with anisotropic friction, Soft Matter 14(4) (2018) 635-642.##[16] A. Ghorbanpour Arani, N. Miralaei, A. Farazin, M. Mohammadimehr, An extensive review of the repair behavior of smart self-healing polymer matrix composites, Journal of Materials Research 38(3) (2023) 617-632.##[17] G. Avashthi, M. Singh, Ultrasound accelerated near-edge functionalized heterogeneous graphene oxide sonocatalyst for surface optical bandwidth efficacy and in situ sonothermocatalysis, New Journal of Chemistry 45(12) (2021) 5463-5483.##[18] Y.J. Kang, Simultaneous measurement of blood pressure and RBC aggregation by monitoring on–off blood flows supplied from a disposable air-compressed pump, Analyst 144(11) (2019) 3556-3566.##[19] L. Xiao, W. Ni, X. Zhao, Y. Guo, X. Li, F. Wang, G. Luo, R. Zhan, X. Xu, A moisture balanced antibacterial dressing loaded with lysozyme possesses antibacterial activity and promotes wound healing, Soft Matter 17(11) (2021) 3162-3173.##[20] J.L. Shamshina, Chitin in ionic liquids: historical insights into the polymer's dissolution and isolation. A review, Green Chemistry 21(15) (2019) 3974-3993.##[21] M. Salehi, M. Mirhaj, N.B. Hoveizavi, M. Tavakoli, N. Mahheidari, Advancements in Wound Dressings: The Role of Chitin/Chitosan-based Biocomposites, Journal of Composites and Compounds 7(23) (2025).##[22] F.L. Mi, Y.B. Wu, S.S. Shyu, J.Y. Schoung, Y.B. Huang, Y.H. Tsai, J.Y. Hao, Control of wound infections using a bilayer chitosan wound dressing with sustainable antibiotic delivery, Journal of Biomedical Materials Research: 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 59(3) (2002) 438-449.##[23] S. Lu, W. Gao, H.Y. Gu, Construction, application and biosafety of silver nanocrystalline chitosan wound dressing, Burns 34(5) (2008) 623-628.##[24] R. Jayakumar, M. Prabaharan, P.S. Kumar, S. Nair, H. Tamura, Biomaterials based on chitin and chitosan in wound dressing applications, Biotechnology advances 29(3) (2011) 322-337.##[25] H. Liu, C. Wang, C. Li, Y. Qin, Z. Wang, F. Yang, Z. Li, J. Wang, A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing, RSC advances 8(14) (2018) 7533-7549.##[26] D. Liang, Z. Lu, H. Yang, J. Gao, R. Chen, Novel asymmetric wettable AgNPs/chitosan wound dressing: in vitro and in vivo evaluation, ACS applied materials and interfaces 8(6) (2016) 3958-3968.##[27] A. Ehterami, M. Salehi, S. Farzamfar, A. Vaez, H. Samadian, H. Sahrapeyma, M. Mirzaii, S. Ghorbani, A. Goodarzi, In vitro and in vivo study of PCL/COLL wound dressing loaded with insulin-chitosan nanoparticles on cutaneous wound healing in rats model, International journal of biological macromolecules 117 (2018) 601-609.##[28] H. Adeli, M.T. Khorasani, M. Parvazinia, Wound dressing based on electrospun PVA/chitosan/starch nanofibrous mats: Fabrication, antibacterial and cytocompatibility evaluation and in vitro healing assay, International journal of biological macromolecules 122 (2019) 238-254.##[29] J. Amirian, Y. Zeng, M.I. Shekh, G. Sharma, F.J. Stadler, J. Song, B. Du, Y. Zhu, In-situ crosslinked hydrogel based on amidated pectin/oxidized chitosan as potential wound dressing for skin repairing, Carbohydrate Polymers 251 (2021) 117005.##[30] Y.-B. Hahn, R. Ahmad, N. Tripathy, Chemical and biological sensors based on metal oxide nanostructures, Chemical Communications 48(84) (2012) 10369-10385.##[31] N.B. Hoveizavi, M. Laghaei, S. Tavakoli, B. Javanmardi, Wearable biosensors incorporating nanocomposites: advancements, applications, and future directions, Journal of Composites and Compounds 6(21) (2024).##[32] L. Cheng, S. Shen, D. Jiang, Q. Jin, P.A. Ellison, E.B. Ehlerding, S. Goel, G. Song, P. Huang, T.E. Barnhart, Chelator-free labeling of metal oxide nanostructures with zirconium-89 for positron emission tomography imaging, ACS nano 11(12) (2017) 12193-12201.##[33] D.W. Moon, Y.H. Park, S.Y. Lee, H. Lim, S. Kwak, M.S. Kim, H. Kim, E. Kim, Y. Jung, H.-S. Hoe, Multiplex protein imaging with secondary ion mass spectrometry using metal oxide nanoparticle-conjugated antibodies, ACS Applied Materials and Interfaces 12(15) (2020) 18056-18064.##[34] H. Xu, Z.P. Aguilar, L. Yang, M. Kuang, H. Duan, Y. Xiong, H. Wei, A. Wang, Antibody conjugated magnetic iron oxide nanoparticles for cancer cell separation in fresh whole blood, Biomaterials 32(36) (2011) 9758-9765.##[35] M. Alavi, M. Rai, Topical delivery of growth factors and metal/metal oxide nanoparticles to infected wounds by polymeric nanoparticles: an overview, Expert Review of Anti-infective Therapy 18(10) (2020) 1021-1032.##[36] L. Chen, Z. Liu, Z. Guo, X.-J. Huang, Regulation of intrinsic physicochemical properties of metal oxide nanomaterials for energy conversion and environmental detection applications, Journal of Materials Chemistry A 8(34) (2020) 17326-17359.##[37] K. Mondal, A. Sharma, Recent advances in electrospun metal-oxide nanofiber based interfaces for electrochemical biosensing, RSC advances 6(97) (2016) 94595-94616.##[38] J. Deng, P. Ren, D. Deng, L. Yu, F. Yang, X. Bao, Highly active and durable non-precious-metal catalysts encapsulated in carbon nanotubes for hydrogen evolution reaction, Energy and Environmental Science 7(6) (2014) 1919-1923.##[39] P. Xiang, K. Petrie, M. Kontopoulou, Z. Ye, R. Subramanian, Tuning structural parameters of polyethylene brushes on silica nanoparticles in surface-initiated ethylene “living” polymerization and effects on silica dispersion in a polyolefin matrix, Polymer Chemistry 4(5) (2013) 1381-1395.##[40] A. Farazin, M. Mohammadimehr, A.H. Ghasemi, H. Naeimi, Design, preparation, and characterization of CS/PVA/SA hydrogels modified with mesoporous Ag 2 O/SiO 2 and curcumin nanoparticles for green, biocompatible, and antibacterial biopolymer film, RSC advances 11(52) (2021) 32775-32791.##[41] M. Mohammadi, M. Khamehchi, Y. Li, Modeling and Monte Carlo simulation of dye-sensitized solar cells based on TiO2/g-C3N4 nanocomposites, Journal of Power Sources 646 (2025) 237313.