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<XML>
  <ISCJOURNAL>
    <YEAR>2025</YEAR>
    <VOL>7</VOL>
    <NO>24</NO>
    <MOSALSAL>24</MOSALSAL>
    <PAGE_NO>4</PAGE_NO>
    <ARTICLES>
      <DOI>10.61882/jcc.7.3.6</DOI>      
      <ARTICLE>
        <LANGUAGE_ID>1</LANGUAGE_ID>
        <TitleF/>
        <TitleE>Investigation of the biphasic effect of lithium ions on HUVEC proliferation in bioactive glass extracts for burn wound regeneration</TitleE>      
        <ABSTRACTS>
          <ABSTRACT>
            <LANGUAGE_ID>1</LANGUAGE_ID>
            <CONTENT>In the current work, we developed a simplified empirical formula to isolate and define the effect of lithium ions (Li+) released from Li-BG on the proliferation of human umbilical vein endothelial cells (HUVECs), based on experiments by Wei et al. We incorporate both culture time and concentration of Li+ (0–65.4 ppm), while providing a hormesis term to partition the characteristic biphasic (bell-shaped) cellular response to lithium. Nonlinear regression to discover best-fit parameters resulted in R2 = 0.8707, and RMSE = 0.0404. Models predict maximum stimulatory effects would occur at ~15 ppm Li⁺, which corresponds with our in vitro results that enhanced HUVEC viability occurred at 1/8–1/16 dilutions of 2.5Li-BG and 3.75Li-BG nanostructured glasses. Additionally, Monte Carlo simulation determined, for the probability of desired cellular outcomes (>80% probability HUVEC OD450 > 0.3), there exists a therapeutic window (10–15 ppm) with maximum likelihood of achieving desired cellular consequences for probabilistic models. Although the full bioactivity of Li-BG is derived from the combined expression of Li+ and Si4+ ions, as demonstrated in the original experimentation, this framework focused exclusively on Li+ allows some predictive modeling to optimize subsequent ion release profiles for next-generation wound dressings that will promote fast healing and sensory recovery.</CONTENT>
            </ABSTRACT>
        </ABSTRACTS>
        <PAGES>
          <PAGE>
            <FPAGE>1</FPAGE>
            <TPAGE>4</TPAGE>
          </PAGE>
        </PAGES>
        <AUTHORS>
          <AUTHOR>
            <Name/>
            <MidName/>
            <Family/>
            <NameE>Azadeh</NameE>
            <MidNameE/>
            <FamilyE>hasanzadeh</FamilyE>
            <Organizations>
              <Organization>Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz</Organization>
              <Organization>Department of Parasitology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz</Organization>
            </Organizations>
            <Countries>
              <Country>Iran</Country>
            </Countries>
            <EMAILS>
              <Email>hasanzadeh.azadeh@yahoo.com</Email>
            </EMAILS>
            <Name/>
            <MidName/>
            <Family/>
            <NameE>Mastafa</NameE>
            <MidNameE/>
            <FamilyE>H. Al-Musawi</FamilyE>
            <Organizations>
              <Organization>Department of Biology, College of Science, Mustansiriyah University, Baghdad</Organization>
            </Organizations>
            <Countries>
              <Country>Iraq</Country>
            </Countries>
            <EMAILS>
              <Email>mustafa.h.j@uomustansiriyah.edu.iq</Email>
            </EMAILS>
          </AUTHOR>
        </AUTHORS>
        <KEYWORDS>
          <KEYWORD>
            <KeyText>Monte Carlo Simulation</KeyText>
          </KEYWORD>
          <KEYWORD>
            <KeyText>Burn Wound</KeyText>
          </KEYWORD>
          <KEYWORD>
            <KeyText>Bioactive Glass</KeyText>                   
          </KEYWORD>
        </KEYWORDS>
        <PDFFileName></PDFFileName>
        <REFRENCES>
          <REFRENCE>
            <REF>[1] Y.-I. Shen, H.-H.G. Song, A.E. Papa, J.A. Burke, S.W. Volk, S. Gerecht, Acellular hydrogels for regenerative burn wound healing: translation from a porcine model, Journal of Investigative Dermatology 135(10) (2015) 2519-2529.##[2] B.S. Atiyeh, S.W.A. Gunn, S.A. Dibo, Metabolic implications of severe burn injuries and their management: a systematic review of the literature, World journal of surgery 32(8) (2008) 1857-1869.##[3] W. Żwierełło, K. Piorun, M. Skórka-Majewicz, A. Maruszewska, J. Antoniewski, I. Gutowska, Burns: classification, pathophysiology, and treatment: a review, International journal of molecular sciences 24(4) (2023) 3749.##[4] W. Adidharma, A.N. Khouri, J.C. Lee, K. Vanderboll, T.A. Kung, P.S. Cederna, S.W. Kemp, Sensory nerve regeneration and reinnervation in muscle following peripheral nerve injury, Muscle and Nerve 66(4) (2022) 384-396.##[5] D. Girard, B. Laverdet, V. Buhé, M. Trouillas, K. Ghazi, M.M. Alexaline, C. Egles, L. Misery, B. Coulomb, J.-J. Lataillade, Biotechnological management of skin burn injuries: challenges and perspectives in wound healing and sensory recovery, Tissue Engineering Part B: Reviews 23(1) (2017) 59-82.##[6] T. Weng, P. Wu, W. Zhang, Y. Zheng, Q. Li, R. Jin, H. Chen, C. You, S. Guo, C. Han, Regeneration of skin appendages and nerves: current status and further challenges, Journal of translational medicine 18(1) (2020) 53.##[7] M. Blais, M. Grenier, F. Berthod, Improvement of nerve regeneration in tissue-engineered skin enriched with schwann cells, Journal of investigative dermatology 129(12) (2009) 2895-2900.##[8] M. Gingras, I. Paradis, F. Berthod, Nerve regeneration in a collagen–chitosan tissue-engineered skin transplanted on nude mice, Biomaterials 24(9) (2003) 1653-1661.##[9] S. Mohammadi, H.R. Rezaie, J. Javadpour, M. Kharaziha, A.R. Khavandi, Fabrication and Characterization of Porosity-Gradient Poly lactic Acid/Bredigite Composite Scaffolds via Fused Deposition Modeling for Bone Tissue Engineering, Revista Latinoamericana de la Papa 29(1) (2025) 540-565.##[10] I. Negut, C. Ristoscu, Bioactive glasses for soft and hard tissue healing applications—a short review, Applied sciences 13(10) (2023) 6151.##[11] T. Mehrabi, A.S. Mesgar, Z. Mohammadi, Bioactive glasses: a promising therapeutic ion release strategy for enhancing wound healing, ACS biomaterials science and engineering 6(10) (2020) 5399-5430.##[12] H. Hu, Y. Tang, L. Pang, C. Lin, W. Huang, D. Wang, W. Jia, Angiogenesis and full-thickness wound healing efficiency of a copper-doped borate bioactive glass/poly (lactic-co-glycolic acid) dressing loaded with vitamin E in vivo and in vitro, ACS applied materials and interfaces 10(27) (2018) 22939-22950.##[13] A.E. Kocman, I. Dag, T. Sengel, E. Soztutar, M. Canbek, The effect of lithium and lithium-loaded hyaluronic acid hydrogel applications on nerve regeneration and recovery of motor functions in peripheral nerve injury, Rendiconti Lincei. Scienze Fisiche e Naturali 31(3) (2020) 889-904.##[14] L.-Q. Zhang, W.-M. Zhang, L. Deng, Z.-X. Xu, W.-B. Lan, J.-H. Lin, Transplantation of a peripheral nerve with neural stem cells plus lithium chloride injection promote the recovery of rat spinal cord injury, Cell transplantation 27(3) (2018) 471-484.##[15] D.P. Kuffler, Can lithium enhance the extent of axon regeneration and neurological recovery following peripheral nerve trauma?, Neural Regeneration Research 17(5) (2022) 948-952.##[16] L. Qi, Y. Tang, W. He, H. Pan, W. Jiang, L. Wang, W. Deng, Lithium chloride promotes neuronal differentiation of rat neural stem cells and enhances neural regeneration in Parkinson’s disease model, Cytotechnology 69(2) (2017) 277-287.##[17] Y.-J. Zhao, H. Qiao, D.-F. Liu, J. Li, J.-X. Li, S.-E. Chang, T. Lu, F.-T. Li, D. Wang, H.-P. Li, Lithium promotes recovery after spinal cord injury, Neural regeneration research 17(6) (2022) 1324-1333.##[18] R. Wei, Z. Zhang, M. Xing, Y. Zhou, J. Chang, Preparation and in vitro evaluation of Lithium-doped bioactive glasses for wound healing with nerve repair potential, Materials Letters 292 (2021) 129629.</REF>
          </REFRENCE>
        </REFRENCES>
      </ARTICLE>
    </ARTICLES>
  </ISCJOURNAL>
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