Skip to main content

Advertisement

SpringerLink
Log in

LiCl Containing Thermosensitive Formulation Improves Hemostasis, Wound Healing, and Hair Regrowth

  • ORIGINAL RESEARCH
  • Published:
Regenerative Engineering and Translational Medicine Aims and scope Submit manuscript

Abstract

Lithium is clinically used for the treatment of the bipolar manic disorder. In this study, we have evaluated its role in the wound healing process on the basis of our previous microarray studies where many genes related to wound healing were upregulated. Formulations containing LiCl, poloxamer 407 (P407), alginate, and serum were prepared so as to make them “active” thermosensitive preparation, which may participate in different phases of wound healing. The formulations were analyzed for their physical properties, hemostasis, healing, hair regrowth, and expression of genes related to wound healing. The formulations showed a thermoreversible property, improved hemostasis in a liver laceration, and improved healing of full-thickness skin wound and hair regrowth in BALB/c mice and Sprague Dawley rat model. Further, we found genes which facilitate repair of the wound, e.g., TGFβ, COX2, and Col1a1, were also upregulated in RT-PCR assay. Particularly, we have detected the potential role of KRTAP10-2 gene in LiCl-induced hair regrowth. These formulations are likely to have application in the treatment of various injuries including accidents, trauma, diabetic wound, radiotherapy, war injuries, etc., where facilitated wound healing is essential.

Lay Summary

Our studies on microarray data analysis of LiCl-treated cells showed upregulation of wound healing genes. A formulation containing LiCl was evaluated in vitro and in vivo, which facilitated various stages of wound healing. The temperature-dependent phase changing property of this formulation makes it effective at places where the temperature remains subzero. The formulation may be prepared with other ingredients such as analgesics and antibiotics and could be packed as per the requirement such as spray, cream, gel, etc.

Future Studies

The formulation may further be evaluated in the GLP (Good Laboratory Practice) setting; this may help in the repurposing of LiCl and other constituents for wound healing purpose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007;25:9–18.

    Article  CAS  Google Scholar 

  2. Monaco JL, Lawrence T. Acute wound healing. An overview. Clin Plast Surg. 2003;30:1–2.

    Article  Google Scholar 

  3. Devi DR, Sandhya P, Hari BNV. Poloxamer: a novel functional molecule for drug delivery and gene therapy. J Pharm Sci Res. 2013;5:159–65.

    Google Scholar 

  4. Yeoman RR, Fox A. Polymers and hydrogels. United States Patent No. US8821933B2. 2014.

  5. Wang S, Yang H, Tang Z, Long G, Huang W. Wound dressing model of human umbilical cord mesenchymal stem cells alginate complex promotes skin wound healing by paracrine signaling. Stem Cells Int. 2016;3269267:1–8.

    Google Scholar 

  6. Shi Y, Shu B, Yang R, Xu Y, Xing B, Liu J, et al. Wnt and notch signaling pathway involved in wound healing by targeting c-Myc and Hes1 separately. Stem Cell Res Ther. 2015;6:120.

    Article  Google Scholar 

  7. Guo S, Arai K, Stins MF, Chuang D, Lo EH. Lithium upregulates vascular endothelial growth factor in brain endothelial cells and astrocytes. Stroke. 2009;40:652–5.

    Article  CAS  Google Scholar 

  8. Focosi D, Azzara A, Kasy RE, Carulli G, Petrini M. Lithium and hematology: established and proposed use. J Leukoc Biol. 2009;85:20–8.

    Article  CAS  Google Scholar 

  9. Petrini M, Vaglini M, Carulli G, Azzara A, Ambrogi F, Bertelli F, et al. Effects of lithium and rubidium on the differentiation of mononuclear cells. Int J Tissue React. 1986;8:391–2.

    CAS  Google Scholar 

  10. Verma YK, Raghav PK, Raj HG, Tripathi RP, Gangenahalli GU. Enhanced heterodimerization of Bax by Bcl-2 mutants improves irradiated cell survival. Apoptosis. 2013;18:212–25.

    Article  CAS  Google Scholar 

  11. Gurudutta GU, Verma YK, Tripathi RP. Novel Bax Antagonist Peptides (Bap) in conjunction with LiCl for decreasing cellular radiation injury. Indian Patent Office application no: 201611006832. 2016.

  12. Satija NK, Sharma D, Afrin F, Tripathi RP. High throughput transcriptome profiling of lithium stimulated human mesenchymal stem cells reveals priming towards osteoblastic lineage. PLoS One. 2013;8:e55769.

    Article  CAS  Google Scholar 

  13. Freshney RI. Culture of animal cells. A manual of basic technique. 3rd ed: Wiley Liss Publication; 1994.

  14. Singh V, Khullar P, Dave PN, Kaur N. Micelles, mixed micelles, and applications of polyoxypropylene (PPO) – polyoxyethylene (PEO) – polyoxypropylene (PPO) triblock polymers. Int J Ind Chem. 2013;4:12.

    Article  CAS  Google Scholar 

  15. Farrar D. Advanced wound repair therapies. A volume in Woodhead Publishing Series in Biomaterials: Woodhead Publishing Limited. 2011;21.

  16. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.

    Article  CAS  Google Scholar 

  17. Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, et al. Integration of biological networks and gene expression data using Cytoscape. Nat Protoc. 2007;2:2366–82.

    Article  CAS  Google Scholar 

  18. Montojo J, Zuberi K, Rodriguez H, Kazi F, Wright G, Donaldson SL, et al. GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop. Bioinformatics. 2010;26:2927–8.

    Article  CAS  Google Scholar 

  19. Bader GD, Hogue CWV. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics. 2003;4:2.

    Article  Google Scholar 

  20. Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology annotation networks. Bioinformatics. 2009;25:1091–3.

    Article  CAS  Google Scholar 

  21. Saxena V, Hussain MD. Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer. Int J Nanomedicine. 2012;7:713–21.

    CAS  Google Scholar 

  22. Khan AW, Kotta S, Ansari SH, Sharma RK, Kumar A, Ali J. Formulation, development, optimization and evaluation of Aloe vera gel for wound healing. Pharmacogn Mag. 2013;9:S6–S10.

    Article  Google Scholar 

  23. Sharma N, Ojha H, Pathak DP, Goel R, Sharma RK. Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity studies of p-tertbutylcalix[4]arene nanoemulsion for radiation decontamination. Life Sci. 2017;168:65–76.

    Article  CAS  Google Scholar 

  24. Murakami Y, Yokoyama M, Nishida H, Tomizawa Y, Kurosawa H. A simple hemostasis model for the quantitative evaluation of hydrogel-based local hemostatic biomaterials on tissue surface. Colloids Surf B: Biointerfaces. 2008;65:186–9.

    Article  CAS  Google Scholar 

  25. Kiran KC, Regis C, Patrick BM, Bernard U, Anne des R, Gaelle V, et al. Combined effect of PLGA and curcumin in wound healing activity. J Control Release. 2013;171:208–15.

    Article  Google Scholar 

  26. Mesri M, Altieri DC. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem. 1991;274:23111–8.

    Article  Google Scholar 

  27. Liang C, Park AY, Guan J. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007;2:329–33.

    Article  CAS  Google Scholar 

  28. Caetano GF, Fronza M, Leite MN, Gomes A, Frade MA. Comparison of collagen content in skin wounds evaluated by biochemical assay and by computer-aided histomorphometric analysis. Pharm Biol. 2016;54:2555–9.

    Article  CAS  Google Scholar 

  29. Shibuya K, Obayashi I, Asakawa S, Minoshima S, Kudoh J, Shimizu N. A cluster if 21 keratin-associated protein genes within introns of another gene on human chromosome 21q22.3. Genomics. 2004;83:679–93.

    Article  CAS  Google Scholar 

  30. Gaisford S, Beezer AE, Mitchell JC, Loh W, Finnie JK, Williams SJ. Diode-array UV spectrometric evidence for a concentration dependent phase transition in dilute aqueous solutions for pluronic F87 (Poloxamer 237). ChemComm. 1995;18:1843–4.

  31. Grissom TE, Fang R. Topical hemostatic agents and dressings in the prehospital setting. Curr Opin Anaesthesiol. 2015;28:210–6.

    Article  CAS  Google Scholar 

  32. Kind GM, Bincs SD, Staren ED, Templeton AJ, Economou SG. Chitosan: evaluation of a new hemostatic agent. Curr Surg. 1990;47:37–9.

    CAS  Google Scholar 

  33. Rhett JM, Ghatnekar GS, Palatinus JA, O’Quinn M, Yost MJ, Gourdie R. Novel therapies for scar reduction and regenerative healing of skin wounds. Trends Biotechnol. 2008;26:173–80.

    Article  CAS  Google Scholar 

  34. Varon D, Shai E. Platelets and their microparticles as key players in pathophysiological responses. J Thromb Haemost. 2015;13:S40–6.

    Article  CAS  Google Scholar 

  35. Cervantes J, Perper M, Wong LL, Eber AE, Fricke ACV, Wikramanayake TC, et al. Effectiveness of platelet-rich plasma doe androgenic alopecia: a review of the literature. Skin Appendage Disord. 2017;4:1–11.

    Article  Google Scholar 

  36. Delaey B, De Waele PGMC. Wound healing compositions and uses. US patent no. US 2005/0079147 A1. 2015.

  37. Grau L. Medical implications of high altitude combat. US Army Med Dep. 2003;1–8.

  38. Shi C, Zhu Y, Su Y, Cheng T. Stem cells and their application in skin-cell therapy. Trends Biotechnol. 2006;24:48–52.

    Article  CAS  Google Scholar 

Download references

Funding

We thank Director, INMAS, for his continuous support. This work was funded by the Defence Research Development Organisation, India, project no. ST/P1/2008/INM/311/1.6.

Author information

Authors and Affiliations

  1. Division of Stem Cell & Gene Therapy Research, Institute of Nuclear Medicine & Allied Sciences, 110054, Delhi, India

    Yogesh Kumar Verma, Ranjan Verma, Ajay Kumar Singh & Gurudutta Gangenahalli

Authors
  1. Yogesh Kumar Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ranjan Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ajay Kumar Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gurudutta Gangenahalli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gurudutta Gangenahalli.

Ethics declarations

Declaration of Interest

This work has been filed for the patent in Indian Patent Office with application number, 201811022395, entitled “Composition for hemostasis and wound healing and implementation thereof.”

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

ESM 1

(DOCX 2732 kb).

ESM 2

(DOCX 13 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Verma, Y.K., Verma, R., Singh, A.K. et al. LiCl Containing Thermosensitive Formulation Improves Hemostasis, Wound Healing, and Hair Regrowth. Regen. Eng. Transl. Med. 7, 362–378 (2021). https://doi.org/10.1007/s40883-020-00148-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40883-020-00148-0

Keywords

Search

Navigation