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Application of combined photobiomodulation and curcumin-loaded iron oxide nanoparticles considerably enhanced repair in an infected, delayed-repair wound model in diabetic rats compared to either treatment alone

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Abstract

Herein, we attempted to evaluate the therapeutic potential of photobiomodulation (PBM) and curcumin-loaded iron nanoparticles (CUR), alone and in combination, on wound closure rate (WCR), microbial flora by measuring colony-forming units (CFUs), the stereological and biomechanical properties of repairing wounds in the maturation stage of the wound healing course in an ischemic infected delayed healing wound model (IIDHWM) of type I diabetic (TIDM) rats. There were four groups: group 1 was the control, group 2 received CUR, rats in group 3 were exposed to PBM (80 Hz, 890 nm, and 0.2 J/cm2), and rats in group 4 received both PBM and CUR (PBM + CUR). We found CFU was decreased in groups 2, 3, and 4 compared to group 1 (p = 0.000 for all). Groups 2, 3, and 4 showed a considerable escalation in WCR compared to group 1 (p = 0.000 for all). In terms of wound strength parameters, substantial increases in bending stiffness and high-stress load were observed in groups 2, 3, and 4 compared to group 1 (p = 0.000 for all). Stereological examinations revealed decreases in neutrophil and macrophage counts and increases in fibroblast counts in groups 2, 3, and 4compared  to group 1 (p = 0.000 for all). Blood vessel counts were more dominant in the PBM and PBM + CUR groups over group 1 (p = 0.000 for all). CFU and wound strength as well as macrophage, neutrophil, and fibroblast counts were found to be improved in the PBM + CUR and PBM groups compared to the CUR group (ranging from p = 0.000 to p < 0.05). Better results were achieved in the PBM + CUR  treatment  over the PBM therapy. We determined therapy with PBM + CUR, PBM alone, and CUR alone substantially accelerated diabetic wound healing in an IIDHWM of TIDM rats compared to control  group. Concomitantly, the PBM + CUR and PBM groups attained significantly enhanced results for WCR, stereological parameters, and wound strength than the CUR group, with the PBM + CUR results being superior to those of the PBM group.

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Statistical analysis of our work was available as a supplementary file.

References

  1. Baynes, H. W. (2015). Classification, pathophysiology, diagnosis and management of diabetes mellitus. Journal of Diabetes Metabolism, 6(5), 1–9.

    Google Scholar 

  2. Gary Sibbald, R., & Woo, K. Y. (2008). The biology of chronic foot ulcers in persons with diabetes. Diabetes/metabolism research and reviews., 24(S1), S25–S30.

    Article  PubMed  Google Scholar 

  3. Steel, A., Reece, J., & Daw, A.-M. (2016). Understanding the relationship between depression and diabetic foot ulcers. Journal of Social Health and Diabetes., 4(01), 017–024.

    Article  Google Scholar 

  4. Armstrong, D. G., Boulton, A. J. M., & Bus, S. A. (2017). Diabetic Foot Ulcers and Their Recurrence. New England Journal of Medicine, 376(24), 2367–2375.

    Article  PubMed  Google Scholar 

  5. Rastogi, A., Goyal, G., Rajesh Kesavan, R., Arun Bal, A., Mangalanadanam, K. H., et al. (2020). Long term outcomes after incident diabetic foot ulcer: multicenter large cohort prospective study (EDI-FOCUS investigators) epidemiology of diabetic foot complications study. Diabetes Research and Clinical Practice, 162, 108–113.

    Article  Google Scholar 

  6. Demirdal, T., & Sen, P. (2018). The significance of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and lymphocyte-monocyte ratio in predicting peripheral arterial disease, peripheral neuropathy, osteomyelitis and amputation in diabetic foot infection. Diabetes research and clinical practice., 144, 118–125.

    Article  PubMed  Google Scholar 

  7. Weiss, U. (2008). Inflammation. Nature, 454(7203), 427.

    Article  CAS  PubMed  Google Scholar 

  8. Oliver, E., McGillicuddy, F., Phillips, C., Toomey, S., & Roche, H. M. (2010). The role of inflammation and macrophage accumulation in the development of obesity-induced type 2 diabetes mellitus and the possible therapeutic effects of long-chain n-3 PUFA. Proceedings of the Nutrition Society., 69(2), 232–243.

    Article  CAS  PubMed  Google Scholar 

  9. Nethi, S. K., Das, S., Patra, C. R., & Mukherjee, S. (2019). Recent advances in inorganic nanomaterials for wound-healing applications. Biomaterials science., 7(7), 2652–2674.

    Article  CAS  PubMed  Google Scholar 

  10. Chopra, H., Dey, P. S., Das, D., Bhattacharya, T., Shah, M., Mubin, S., et al. (2021). Curcumin nanoparticles as promising therapeutic agents for drug targets. Molecules, 26(16), 4998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Karri, V. V. S. R., Kuppusamy, G., Talluri, S. V., Mannemala, S. S., Kollipara, R., Wadhwani, A. D., et al. (2016). Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing. International journal of biological macromolecules., 93, 1519–1529.

    Article  CAS  PubMed  Google Scholar 

  12. Anand, P., Kunnumakkara, A. B., Newman, R. A., & Aggarwal, B. B. (2007). Bioavailability of curcumin: problems and promises. Molecular pharmaceutics., 4(6), 807–818.

    Article  CAS  PubMed  Google Scholar 

  13. Justin, C., Samrot, A. V., Sahithya, C. S., Bhavya, K. S., & Saipriya, C. (2018). Preparation, characterization and utilization of coreshell super paramagnetic iron oxide nanoparticles for curcumin delivery. PLoS ONE, 13(7), e0200440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Naserzadeh, P., Hafez, A. A., Abdorahim, M., Abdollahifar, M. A., Shabani, R., Peirovi, H., et al. (2018). Curcumin loading potentiates the neuroprotective efficacy of Fe3O4 magnetic nanoparticles in cerebellum cells of schizophrenic rats. Biomedicine & Pharmacotherapy., 108, 1244–1252.

    Article  CAS  Google Scholar 

  15. Moradi, A., Kheirollahkhani, Y., Fatahi, P., Abdollahifar, M.-A., Amini, A., Naserzadeh, P., et al. (2019). An improvement in acute wound healing in mice by the combined application of photobiomodulation and curcumin-loaded iron particles. Lasers in Medical Science., 34(4), 779–791.

    Article  PubMed  Google Scholar 

  16. Abhari, S. M. F., Khanbabaei, R., Roodbari, N. H., Parivar, K., & Yaghmaei, P. (2020). Curcumin-loaded super-paramagnetic iron oxide nanoparticle affects on apoptotic factors expression and histological changes in a prepubertal mouse model of polycystic ovary syndrome-induced by dehydroepiandrosterone-A molecular and stereological study. Life sciences., 249, 117515.

    Article  Google Scholar 

  17. Saikia, C., Das, M. K., Ramteke, A., & Maji, T. K. (2016). Effect of crosslinker on drug delivery properties of curcumin loaded starch coated iron oxide nanoparticles. International journal of biological macromolecules., 93, 1121–1132.

    Article  CAS  PubMed  Google Scholar 

  18. Dayya, D., O’Neill, O., Habib, N., Moore, J., Iyer, K., & Huedo-Medina, T. B. (2022). Debridement of diabetic foot ulcers: public health and clinical implications–a systematic review, meta-analysis, and meta-regression. BMJ Surgery, Interventions, & Health Technologies. https://doi.org/10.1136/bmjsit-2021-000081.

    Article  Google Scholar 

  19. Fard, A. S., Esmaelzadeh, M., & Larijani, B. (2007). Assessment and treatment of diabetic foot ulcer. International journal of clinical practice., 61(11), 1931–1938.

    Article  CAS  PubMed  Google Scholar 

  20. Carroll, L., & Humphreys, T. R. (2006). LASER-tissue interactions. Clinics in dermatology, 24(1), 2–7.

    Article  PubMed  Google Scholar 

  21. Avci, P., Gupta, A., Sadasivam, M., Vecchio, D., Pam, Z., Pam, N., et al. (2013). Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring. Seminars in cutaneous medicine and surgery. UK: NIH Public Access.

    Google Scholar 

  22. Oyebode, O., Houreld, N. N., & Abrahamse, H. (2021). Photobiomodulation in diabetic wound healing: A review of red and near-infrared wavelength applications. Cell Biochemistry and Function., 39(5), 596–612.

    Article  CAS  PubMed  Google Scholar 

  23. Mostafavinia, A., Masteri Farahani, R., Abdollahifar, M.-A., Ghatrehsamani, M., Ghoreishi, S. K., Hajihossainlou, B., et al. (2018). Evaluation of the effects of photobiomodulation on partial osteotomy in streptozotocin-induced diabetes in rats. Photomedicine and Laser Surgery., 36(8), 406–414.

    Article  CAS  PubMed  Google Scholar 

  24. Mostafavinia, A., Farahani, R. M., Abbasian, M., Farahani, M. V., Fridoni, M., Zandpazandi, S., et al. (2015). Effect of pulsed wave low-level laser therapy on tibial complete osteotomy model of fracture healing with an intramedullary fixation. Iranian Red Crescent Medical Journal. https://doi.org/10.5812/ircmj.32076.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Khosravipour, A., Amini, A., Farahani, R. M., Zare, F., Mostafavinia, A., Fallahnezhad, S., et al. (2020). Preconditioning adipose-derived stem cells with photobiomodulation significantly increased bone healing in a critical size femoral defect in rats. Biochemical and biophysical research communications., 531(2), 105–111.

    Article  CAS  PubMed  Google Scholar 

  26. Gazor, R., Asgari, M., Abdollajhifar, M.-A., Kiani, P., Zare, F., Fathabady, F. F., et al. (2021). Simultaneous treatment of photobiomodulation and demineralized bone matrix with adipose-derived stem cells improve bone healing in an osteoporotic bone defect. Journal of Lasers in Medical Sciences, 12(1), E41.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Asgari, M., Abdollahifar, M.-A., Gazor, R., Salmani, T., Khosravipour, A., Mahmoudi, Y., et al. (2022). Photobiomodulation and stem cell on repair of osteoporotic bones. Photobiomodulation, Photomedicine, and Laser Surgery., 40(4), 261–272.

    Article  CAS  PubMed  Google Scholar 

  28. Khosravipour, A., Mostafavinia, A., Amini, A., Gazor, R., Zare, F., Fallahnezhad, S., et al. (2022). Different protocols of combined application of photobiomodulation in vitro and in vivo plus adipose-derived stem cells improve the healing of bones in critical size defects in rat models. Journal of Lasers in Medical Sciences. https://doi.org/10.34172/jlms.2022.10.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Amini, A., Soleimani, H., Abdollhifar, M. A., Moradi, A., Ghoreishi, S. K., Chien, S., et al. (2019). Stereological and gene expression examinations on the combined effects of photobiomodulation and curcumin on wound healing in type one diabetic rats. Journal of cellular biochemistry., 120(10), 17994–18004.

    Article  CAS  PubMed  Google Scholar 

  30. Moradi, A., Kheirollahkhani, Y., Fatahi, P., Abdollahifar, M. A., Amini, A., Naserzadeh, P., et al. (2019). An improvement in acute wound healing in mice by the combined application of photobiomodulation and curcumin-loaded iron particles. Lasers in Medical Science, 34(4), 779–791.

    Article  PubMed  Google Scholar 

  31. Ebrahimpour-Malekshah, R., Amini, A., Zare, F., Mostafavinia, A., Davoody, S., Deravi, N., et al. (2020). Combined therapy of photobiomodulation and adipose-derived stem cells synergistically improve healing in an ischemic, infected and delayed healing wound model in rats with type 1 diabetes mellitus. BMJ Open Diabetes Research & Care. https://doi.org/10.1136/bmjdrc-2019-001033.

    Article  Google Scholar 

  32. Kamar, S. S., Abdel-Kader, D. H., & Rashed, L. A. (2019). Beneficial effect of curcumin nanoparticles-hydrogel on excisional skin wound healing in type-i diabetic rat: histological and immunohistochemical studies. Annals of Anatomy—Anatomischer Anzeiger, 222, 94–102.

    Article  Google Scholar 

  33. Karri, V. V., Kuppusamy, G., Talluri, S. V., Mannemala, S. S., Kollipara, R., Wadhwani, A. D., et al. (2016). Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing. International Journal of Biological Macromolecules, 93(Pt B), 1519–1529.

    Article  CAS  PubMed  Google Scholar 

  34. Liu, J., Chen, Z., Wang, J., Li, R., Li, T., Chang, M., et al. (2018). Encapsulation of curcumin nanoparticles with MMP9-responsive and thermos-sensitive hydrogel improves diabetic wound healing. ACS Applied Materials and Interfaces., 10(19), 16315–16326.

    Article  CAS  PubMed  Google Scholar 

  35. Li, F., Shi, Y., Liang, J., & Zhao, L. (2019). Curcumin-loaded chitosan nanoparticles promote diabetic wound healing via attenuating inflammation in a diabetic rat model. Journal of biomaterials applications., 34(4), 476–486.

    Article  CAS  PubMed  Google Scholar 

  36. Taghavifar, S., Afroughi, F., & Saadati, K. M. (2022). Curcumin nanoparticles improved diabetic wounds infected with methicillin-resistant staphylococcus aureus sensitized with HAMLET. The International Journal of Lower Extremity Wounds., 21(2), 141–153.

    Article  CAS  PubMed  Google Scholar 

  37. Lee, S. Y., Jeon, S., Kwon, Y. W., Kwon, M., Kang, M. S., Seong, K. Y., et al. (2022). Combinatorial wound healing therapy using adhesive nanofibrous membrane equipped with wearable LED patches for photobiomodulation. Science Advances, 8(15), eabn1646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zaccaron, R. P., Barbieri, R. T., Mendes, C., Venturini, L. M., Alves, N., Mariano, S. S., et al. (2022). Photobiomodulation associated with lipid nanoparticles and hyaluronic acid accelerate the healing of excisional wounds. Journal of Biomaterials Applications., 15, 8853282221109344.

    Google Scholar 

  39. Lee, S. Y., Seong, I. W., Kim, J. S., Cheon, K. A., Gu, S. H., Kim, H. H., et al. (2011). Enhancement of cutaneous immune response to bacterial infection after low-level light therapy with 1072 nm infrared light: a preliminary study. Journal of Photochemistry and Photobiology B: Biology, 105(3), 175–182.

    Article  CAS  PubMed  Google Scholar 

  40. Karkada, G., Maiya, G. A., Houreld, N. N., Arany, P., Rao, K. G. M., Adiga, S., et al. (2020). Effect of photobiomodulation therapy on inflammatory cytokines in healing dynamics of diabetic wounds: a systematic review of preclinical studies. Archives of physiology and biochemistry. https://doi.org/10.1080/13813455.2020.1861025.

    Article  PubMed  Google Scholar 

  41. Moradi, A., Zare, F., Mostafavinia, A., Safaju, S., Shahbazi, A., Habibi, M., Abdollahifar, M. A., Hashemi, S. M., Amini, A., Ghoreishi, S. K., Chien, S., Hamblin, M. R., Kouhkheil, R., Bayat, M. (2020). Photobiomodulation plus adipose-derived stem cells improve healing of ischemic infected wounds in type 2 diabetic rats. Scientific Reports, 10(1), 1206. https://doi.org/10.1038/s41598-020-58099-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kim, H., Kim, D. E., Han, G., Lim, N. R., Kim, E. H., Jang, Y., et al. (2022). Harnessing the natural healing power of colostrum: bovine milk-derived extracellular vesicles from colostrum facilitating the transition from inflammation to tissue regeneration for accelerating cutaneous wound healing. Advanced Healthcare Materials., 11(6), 2102027.

    Article  CAS  Google Scholar 

  43. Glass, G. E. (2021). Photobiomodulation: a review of the molecular evidence for low level light therapy. Journal of Plastic, Reconstructive & Aesthetic Surgery., 74(5), 1050–1060.

    Article  Google Scholar 

  44. Jere, S. W., Houreld, N. N., & Abrahamse, H. (2018). Photobiomodulation at 660nm stimulates proliferation and migration of diabetic wounded cells via the expression of epidermal growth factor and the JAK/STAT pathway. Journal of Photochemicals and Photobiology B., 179, 74–83.

    Article  CAS  Google Scholar 

  45. Karkada, G., Maiya, G. A., Houreld, N. N., Arany, P., Rao Kg, M., Adiga, S., et al. (2020). Effect of photobiomodulation therapy on inflammatory cytokines in healing dynamics of diabetic wounds: a systematic review of preclinical studies. Archives of Physiology and Biochemistry., 23, 1–8.

    Google Scholar 

  46. Dadpay, M., Sharifian, Z., Bayat, M., Bayat, M., & Dabbagh, A. (2012). Effects of pulsed infra-red low level-laser irradiation on open skin wound healing of healthy and streptozotocin-induced diabetic rats by biomechanical evaluation. Journal of Photochemistry and Photobiology B: Biology., 111, 1–8.

    Article  CAS  PubMed  Google Scholar 

  47. Ma, H., Yang, J.-P., Tan, R. K., Lee, H.-W., & Han, S.-K. (2018). Effect of low-level laser therapy on proliferation and collagen synthesis of human fibroblasts in Vitro. Journal of wound management and research., 14(1), 1–6.

    Article  Google Scholar 

  48. George, S., Hamblin, M. R., & Abrahamse, H. (2018). Effect of red light and near infrared laser on the generation of reactive oxygen species in primary dermal fibroblasts. Journal of Photochemistry and Photobiology B: Biology., 188, 60–68.

    Article  CAS  PubMed  Google Scholar 

  49. Skopin, M. D., & Molitor, S. C. (2009). Effects of near-infrared laser exposure in a cellular model of wound healing. Photodermatology, photoimmunology & photomedicine., 25(2), 75–80.

    Article  Google Scholar 

  50. Zhu, Q., Xiao, S., Hua, Z., Yang, D., Hu, M., Zhu, Y.-T., et al. (2021). Near infrared (NIR) light therapy of eye diseases: A review. International Journal of Medical Sciences., 18(1), 109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ando, T., Xuan, W., Xu, T., Dai, T., Sharma, S. K., Kharkwal, G. B., et al. (2011). Comparison of therapeutic effects between pulsed and continuous wave 810-nm wavelength laser irradiation for traumatic brain injury in mice. PLoS ONE, 6(10), e26212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Dai, T., Tegos, G. P., Zhiyentayev, T., Mylonakis, E., & Hamblin, M. R. (2010). Photodynamic therapy for methicillin-resistant Staphylococcus aureus infection in a mouse skin abrasion model. Lasers in Surgery and Medicine: The Official Journal of the American Society for Laser Medicine and Surgery., 42(1), 38–44.

    Article  Google Scholar 

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Funding

Our research was economically supported by the Research Department of the medical faculty at SBMU (Grant No.: 30491, (IR.SBMU.MSP.REC.1400. 675,). This article was extracted from the thesis (IR.SBMU.AEC.1401.034) written by Mr. Hamidreza Omidi.

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Authors and Affiliations

  1. Department of Biology and Anatomical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hamidreza Omidi, Abdollah Amini, Fatemeh Fadaei Fathabady, Houssein Ahmadi, Fahimeh Ghasemi Moravej & Mohammad Bayat

  2. School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Kaysan Sohrabi & Mohammadali Asghari

  3. Department of Anatomical Sciences and Cognitive Neuroscience, School of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Atarodalsadat Mostafavinia

  4. Department of Anatomy, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Mansooreh Mirzaei

  5. College of Pharmacy, University of Kentucky, Lexington, KY, 40536, USA

    Fatemehalsadat Rezaei

  6. Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Latif Gachkar

  7. Department of Infectious Diseases, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Latif Gachkar

  8. Price Institute of Surgical Research, University of Louisville and Noveratech LLC, Louisville, KY, USA

    Sufan Chien & Mohammad Bayat

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  1. Hamidreza Omidi
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Contributions

MB wrote the manuscript. HO, KS, AM, HA, MM, FG, MA, and FR performed the experiments. AA, FF, LG, and SC added their comments. AM completed the statistical methods. All authors approved the manuscript.

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Correspondence to Abdollah Amini or Mohammad Bayat.

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This investigation was permitted by the Clinical Morals office of SBMU (IR.SBMU.MSP.REC.1400. 675, and IR.SBMU.AEC.1401.034).

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Omidi, H., Sohrabi, K., Amini, A. et al. Application of combined photobiomodulation and curcumin-loaded iron oxide nanoparticles considerably enhanced repair in an infected, delayed-repair wound model in diabetic rats compared to either treatment alone. Photochem Photobiol Sci 22, 1791–1807 (2023). https://doi.org/10.1007/s43630-023-00411-7

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