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Preparation, Characterization, and Wound Healing Assessment of Curcumin-Loaded M-MOF (M = Cu, Zn)@Polycaprolactone Nanocomposite Sponges

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Abstract

The fabrication of multifunctional scaffolds has attracted much attention in biological fields. In this research, some novel composites of Cu(II) or Zn(II) metal–organic framework (M-MOF) and polycaprolactone (PCL), M-MOF@PCL, have been fabricated as multifunctional scaffolds for application in the tissue engineering (TE) field. The porous three-dimensional sponges were prepared by the salt leaching method. Then, the M-MOF@PCL composite sponges have been prepared by in situ synthesis of M-MOF in the presence of the as-obtained PCL sponge to gain a new compound with proper features for biological applications. Finally, curcumin was attached to the M-MOF@PCL as a bioactive compound that can act as a wound-healing agent, anti-oxidant, and anti-inflammatory. The presence of the M-MOF in final composites was investigated by different methods such as FTIR (Fourier-transform infrared), XRD (X-ray diffraction), SEM (scanning electron microscope), EDS (energy-dispersive X-ray spectroscopy), and TEM (transmission electron microscope). SEM images confirmed the porous structure of the as-obtained composites. According to the EDS and TEM images, M-MOFs were uniformly incorporated throughout the PCL sponges. The water sorption capacities of the blank PCL, Cu-MOF@PCL, and Zn-MOF@PCL were determined as 56%, 155%, and 119%, respectively. In vivo investigation on a third-degree burn model in adult male Wistar rats exhibited an accelerated wound healing for Cu-MOF@PCL compared to with Zn-MOF@PCL and the control group.

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References

  1. Luo, H., Cha, R., Li, J., Hao, W., Zhang, Y., & Zhou, F. (2019). Advances in tissue engineering of nanocellulose-based scaffolds: A review. Carbohydrate Polymers, 224, 115144. https://doi.org/10.1016/j.carbpol.2019.115144

    Article  CAS  PubMed  Google Scholar 

  2. Annabi, N., Rana, D., Sani, E. S., Portillo-Lara, R., Gifford, J. L., Fares, M. M., et al. (2017). Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing. Biomaterials, 139, 229–243. https://doi.org/10.1016/j.biomaterials.2017.05.011

    Article  CAS  PubMed  Google Scholar 

  3. Sharma, K., Porat, Z. E., & Gedanken, A. (2021). Designing natural polymer-based capsules and spheres for biomedical applications—a review. Polymers, 13(24), 4307. https://doi.org/10.3390/polym13244307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Simionescu, B. C., & Ivanov, D. (2016). Natural and synthetic polymers for designing composite materials. In Handbook of bioceramics and biocomposites (pp. 233–286). Springer. https://doi.org/10.1007/978-3-319-12460-5_11

    Chapter  Google Scholar 

  5. Anwunobi, A. P., & Emeje, M. O. (2011). Recent applications of natural polymers in nanodrug delivery. Journal of Nanomedicine & Nanotechnology, 4(002). https://doi.org/10.4172/2157-7439.S4-002

  6. Fadaie, M., Mirzaei, E., Geramizadeh, B., & Asvar, Z. (2018). Incorporation of nanofibrillated chitosan into electrospun PCL nanofibers makes scaffolds with enhanced mechanical and biological properties. Carbohydrate Polymers, 199, 628–640. https://doi.org/10.1016/j.carbpol.2018.07.061

    Article  CAS  PubMed  Google Scholar 

  7. Chandika, P., Oh, G. W., Heo, S. Y., Kim, S. C., Kim, T. H., Kim, M. S., & Jung, W. K. (2021). Electrospun porous bilayer nano-fibrous fish collagen/PCL bio-composite scaffolds with covalently cross-linked chitooligosaccharides for full-thickness wound-healing applications. Materials Science and Engineering: C, 121, 111871. https://doi.org/10.1016/j.msec.2021.111871

    Article  CAS  PubMed  Google Scholar 

  8. Mohamed, R. M., & Yusoh, K. (2016). A review on the recent research of polycaprolactone (PCL). Advanced Materials Research, 1134, 249–255. https://doi.org/10.4028/www.scientific.net/AMR.1134.249

    Article  Google Scholar 

  9. Jiao, Z., Luo, B., Xiang, S., Ma, H., Yu, Y., & Yang, W. (2019). 3D printing of HA/PCL composite tissue engineering scaffolds. Advanced Industrial and Engineering Polymer Research, 2(4), 196–202. https://doi.org/10.1016/j.aiepr.2019.09.003

    Article  Google Scholar 

  10. Fox, K., Ratwatte, R., Booth, M. A., Tran, H. M., & Tran, P. A. (2020). High nanodiamond content-PCL composite for tissue engineering scaffolds. Nanomaterials, 10(5), 948. https://doi.org/10.3390/nano10050948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Prahastuti, S., Hidayat, M., Hasianna, S. T., Widowati, W., Amalia, A., Yusepany, D. T., & Kusuma, H. S. W. (2019). Antioxidant potential ethanolic extract of Glycine max (l.) Merr. Var. Detam and daidzein. In Journal of Physics: Conference Series (Vol. 1374, No. 1, p. 012020). IOP Publishing. https://doi.org/10.1088/1742-6596/1374/1/012020

    Chapter  Google Scholar 

  12. Sani, I. S., Rezaei, M., Khoshfetrat, A. B., & Razzaghi, D. (2021). Preparation and characterization of polycaprolactone/chitosan-g-polycaprolactone/hydroxyapatite electrospun nanocomposite scaffolds for bone tissue engineering. International Journal of Biological Macromolecules, 182, 1638–1649. https://doi.org/10.1016/j.ijbiomac.2021.05.163

    Article  CAS  Google Scholar 

  13. Chen, L., Zhang, X., Cheng, X., Xie, Z., Kuang, Q., & Zheng, L. (2020). The function of metal–organic frameworks in the application of MOF-based composites. Nanoscale Advances, 2(7), 2628–2647. https://doi.org/10.1039/D0NA00184H

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Safaei, M., Foroughi, M. M., Ebrahimpoor, N., Jahani, S., Omidi, A., & Khatami, M. (2019). A review on metal-organic frameworks: Synthesis and applications. TrAC Trends in Analytical Chemistry, 118, 401–425. https://doi.org/10.1016/j.trac.2019.06.007

    Article  CAS  Google Scholar 

  15. Liu, B., Jiang, M., Zhu, D., Zhang, J., & Wei, G. (2022). Metal-organic frameworks functionalized with nucleic acids and amino acids for structure-and function-specific applications: A tutorial review. Chemical Engineering Journal, 428, 131118. https://doi.org/10.1016/j.cej.2021.131118

    Article  CAS  Google Scholar 

  16. Safdar Ali, R., Meng, H., & Li, Z. (2021). Zinc-based metal-organic frameworks in drug delivery, cell imaging, and sensing. Molecules, 27(1), 100. https://doi.org/10.3390/molecules27010100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Keskin, S., & Kızılel, S. (2011). Biomedical applications of metal organic frameworks. Industrial & Engineering Chemistry Research, 50(4), 1799–1812. https://doi.org/10.1021/ie101312k

    Article  CAS  Google Scholar 

  18. Singh, N., Qutub, S., & Khashab, N. M. (2021). Biocompatibility and biodegradability of metal organic frameworks for biomedical applications. Journal of Materials Chemistry B. https://doi.org/10.1039/D1TB01044A

  19. Nakhaei, M., Akhbari, K., Kalati, M., & Phuruangrat, A. (2021). Antibacterial activity of three zinc-terephthalate MOFs and its relation to their structural features. Inorganica Chimica Acta, 522, 120353. https://doi.org/10.1016/j.ica.2021.120353

    Article  CAS  Google Scholar 

  20. Li, Y., Liu, X., Tan, L., Cui, Z., Yang, X., Zheng, Y., et al. (2018). Rapid sterilization and accelerated wound healing using Zn2+ and graphene oxide modified g-C3N4 under dual light irradiation. Advanced Functional Materials, 28(30), 1800299. https://doi.org/10.1002/adfm.201800299

    Article  CAS  Google Scholar 

  21. Ramezani, M. R., Ansari-Asl, Z., Hoveizi, E., & Kiasat, A. R. (2020). Fabrication and characterization of Fe (III) metal-organic frameworks incorporating polycaprolactone nanofibers: potential scaffolds for tissue engineering. Fibers and Polymers, 21(5), 1013–1022. https://doi.org/10.1007/s12221-020-9523-6

    Article  CAS  Google Scholar 

  22. Zheng, Q., Li, J., Yuan, W., Liu, X., Tan, L., Zheng, Y., et al. (2019). Metal–organic frameworks incorporated polycaprolactone film for enhanced corrosion resistance and biocompatibility of Mg Alloy. ACS Sustainable Chemistry & Engineering, 7(21), 18114–18124. https://doi.org/10.1021/acssuschemeng.9b05196

    Article  CAS  Google Scholar 

  23. Liu, M., Wang, L., Zheng, X., & Xie, Z. (2017). Zirconium-based nanoscale metal–organic framework/poly (ε-caprolactone) mixed-matrix membranes as effective antimicrobials. ACS Applied Materials & Interfaces, 9(47), 41512–41520. https://doi.org/10.1021/acsami.7b15826

    Article  CAS  Google Scholar 

  24. Maiti, P., & Dunbar, G. L. (2018). Use of curcumin, a natural polyphenol for targeting molecular pathways in treating age-related neurodegenerative diseases. International Journal of Molecular Sciences, 19(6), 1637. https://doi.org/10.3390/ijms19061637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Urošević, M., Nikolić, L., Gajić, I., Nikolić, V., Dinić, A., & Miljković, V. (2022). Curcumin: Biological activities and modern pharmaceutical forms. Antibiotics, 11(2), 135. https://doi.org/10.3390/antibiotics11020135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lestari, W. W., Arvinawati, M., Martien, R., & Kusumaningsih, T. (2018). Green and facile synthesis of MOF and nano MOF containing zinc (II) and benzen 1, 3, 5-tri carboxylate and its study in ibuprofen slow-release. Materials Chemistry and Physics, 204, 141–146. https://doi.org/10.1016/j.matchemphys.2017.10.034

    Article  CAS  Google Scholar 

  27. Emam, H. E., Darwesh, O. M., & Abdelhameed, R. M. (2018). In-growth metal organic framework/synthetic hybrids as antimicrobial fabrics and its toxicity. Colloids and Surfaces B: Biointerfaces, 165, 219–228. https://doi.org/10.1016/j.colsurfb.2018.02.028

    Article  CAS  PubMed  Google Scholar 

  28. Gandara-Loe, J., Souza, B. E., Missyul, A., Giraldo, G., Tan, J. C., & Silvestre-Albero, J. (2020). MOF-based polymeric nanocomposite films as potential materials for drug delivery devices in ocular therapeutics. ACS Applied Materials & Interfaces, 12(27), 30189–30197. https://doi.org/10.1021/acsami.0c07517

    Article  CAS  Google Scholar 

  29. Sanjeevi, S., Shanmugam, V., Kumar, S., Ganesan, V., Sas, G., Johnson, D. J., et al. (2021). Effects of water absorption on the mechanical properties of hybrid natural fibre/phenol formaldehyde composites. Scientific Reports, 11(1), 1–11. https://doi.org/10.1038/s41598-021-92457-9

    Article  CAS  Google Scholar 

  30. Haghshenas, M., Hoveizi, E., Mohammadi, T., & Kazemi Nezhad, S. R. (2019). Use of embryonic fibroblasts associated with graphene quantum dots for burn wound healing in Wistar rats. In Vitro Cellular & Developmental Biology-Animal, 55(4), 312–322. https://doi.org/10.1007/s11626-019-00331-w

    Article  CAS  Google Scholar 

  31. Ren, G., He, Y., Liu, C., Ni, F., Luo, X., Shi, J., et al. (2022). Encapsulation of curcumin in ZEIN-HTCC complexes: Physicochemical characterization, in vitro sustained release behavior and encapsulation mechanism. LWT, 155, 112909. https://doi.org/10.1016/j.lwt.2021.112909

    Article  CAS  Google Scholar 

  32. Balu, R., Kumar, T. S., Ramalingam, M., & Ramakrishna, S. (2011). Electrospun Polycaprolactone/Poly (1, 4-butylene adipate-co-polycaprolactam) blends: Potential biodegradable scaffold for bone tissue regeneration. Journal of Biomaterials and Tissue Engineering, 1(1), 30–39. https://doi.org/10.1166/jbt.2011.1004

    Article  Google Scholar 

  33. Kemala, T., Budianto, E., & Soegiyono, B. (2012). Preparation and characterization of microspheres based on blend of poly (lactic acid) and poly (ɛ-caprolactone) with poly (vinyl alcohol) as emulsifier. Arabian Journal of Chemistry, 5(1), 103–108. https://doi.org/10.1016/j.arabjc.2010.08.003

    Article  CAS  Google Scholar 

  34. Hosseini, M. S., Zeinali, S., & Sheikhi, M. H. (2016). Fabrication of capacitive sensor based on Cu-BTC (MOF-199) nanoporous film for detection of ethanol and methanol vapors. Sensors and Actuators B: Chemical, 230, 9–16. https://doi.org/10.1016/j.snb.2016.02.008

    Article  CAS  Google Scholar 

  35. Loera-Serna, S., Oliver-Tolentino, M. A., de Lourdes López-Núñez, M., Santana-Cruz, A., Guzmán-Vargas, A., Cabrera-Sierra, R., et al. (2012). Electrochemical behavior of [Cu3 (BTC) 2] metal–organic framework: the effect of the method of synthesis. Journal of Alloys and Compounds, 540, 113–120. https://doi.org/10.1016/j.jallcom.2012.06.030

    Article  CAS  Google Scholar 

  36. Homayoonnia, S., & Zeinali, S. (2016). Design and fabrication of capacitive nanosensor based on MOF nanoparticles as sensing layer for VOCs detection. Sensors and Actuators B: Chemical, 237, 776–786. https://doi.org/10.1016/j.snb.2016.06.152

    Article  CAS  Google Scholar 

  37. Wang, X., Ma, X., Wang, H., Huang, P., Du, X., & Lu, X. (2017). A zinc (II) benzenetricarboxylate metal organic framework with unusual adsorption properties, and its application to the preconcentration of pesticides. Microchimica Acta, 184(10), 3681–3687. https://doi.org/10.1007/s00604-017-2382-1

    Article  CAS  Google Scholar 

  38. Sindhu, K., Rajaram, A., Sreeram, K. J., & Rajaram, R. (2014). Curcumin conjugated gold nanoparticle synthesis and its biocompatibility. RSC Advances, 4(4), 1808–1818. https://doi.org/10.1039/C3RA45345F

    Article  Google Scholar 

  39. Singh, P. K., Wani, K., Kaul-Ghanekar, R., Prabhune, A., & Ogale, S. (2014). From micron to nano-curcumin by sophorolipid co-processing: highly enhanced bioavailability, fluorescence, and anti-cancer efficacy. RSC Advances, 4(104), 60334–60341. https://doi.org/10.1039/C4RA07300B

    Article  CAS  Google Scholar 

  40. Kundu, S., & Nithiyanantham, U. (2013). In situ formation of curcumin stabilized shape-selective Ag nanostructures in aqueous solution and their pronounced SERS activity. RSC Advances, 3(47), 25278–25290. https://doi.org/10.1039/C3RA44471F

    Article  CAS  Google Scholar 

  41. Gotthardt, M. A., Schoch, R., Wolf, S., Bauer, M., & Kleist, W. (2015). Synthesis and characterization of bimetallic metal–organic framework Cu–Ru-BTC with HKUST-1 structure. Dalton Transactions, 44(5), 2052–2056. https://doi.org/10.1039/C4DT02491E

    Article  CAS  PubMed  Google Scholar 

  42. Fadaie, M., & Mirzaei, E. (2018). Nanofibrillated chitosan/polycaprolactone bionanocomposite scaffold with improved tensile strength and cellular behavior. Nanomedicine Journal, 5(2), 77–89. https://doi.org/10.22038/nmj.2018.005.004

    Article  CAS  Google Scholar 

  43. Hsu, K. H., Fang, S. P., Lin, C. L., Liao, Y. S., Yoon, Y. K., & Chauhan, A. (2016). Hybrid electrospun polycaprolactone mats consisting of nanofibers and microbeads for extended release of dexamethasone. Pharmaceutical Research, 33(6), 1509–1516. https://doi.org/10.1007/s11095-016-1894-4

    Article  CAS  PubMed  Google Scholar 

  44. Ma, D., Peh, S. B., Han, G., & Chen, S. B. (2017). Thin-film nanocomposite (TFN) membranes incorporated with super-hydrophilic metal–organic framework (MOF) UiO-66: toward enhancement of water flux and salt rejection. ACS Applied Materials & Interfaces, 9(8), 7523–7534. https://doi.org/10.1021/acsami.6b14223

    Article  CAS  Google Scholar 

  45. Heydari, P., Zargar Kharazi, A., Asgary, S., & Parham, S. (2022). Comparing the wound healing effect of a controlled release wound dressing containing curcumin/ciprofloxacin and simvastatin/ciprofloxacin in a rat model: A preclinical study. Journal of Biomedical Materials Research Part A, 110(2), 341–352. https://doi.org/10.1002/jbm.a.37292

    Article  CAS  PubMed  Google Scholar 

  46. Menon, V. P., & Sudheer, A. R. (2007). Antioxidant and anti-inflammatory properties of curcumin. In The molecular targets and therapeutic uses of curcumin in health and disease, pp. 105–125. https://doi.org/10.1007/978-0-387-46401-5_3

  47. Marzo, T., & La Mendola, D. (2021). The effects on angiogenesis of relevant inorganic chemotherapeutics. Current Topics In Medicinal Chemistry, 21(1), 73–86. https://doi.org/10.2174/1568026620666201126163436

    Article  CAS  PubMed  Google Scholar 

  48. Naletova, I., Greco, V., Sciuto, S., Attanasio, F., & Rizzarelli, E. (2021). Ionophore ability of carnosine and its trehalose conjugate assists copper signal in triggering brain-derived neurotrophic factor and vascular endothelial growth factor activation in vitro. International Journal of Molecular Sciences, 22(24), 13504. https://doi.org/10.3390/ijms222413504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cangul, I. T., Gul, N. Y., Topal, A., & Yilmaz, R. (2006). Evaluation of the effects of topical tripeptide-copper complex and zinc oxide on open-wound healing in rabbits. Veterinary Dermatology, 17(6), 417–423. https://doi.org/10.1111/j.1365-3164.2006.00551.x

    Article  PubMed  Google Scholar 

  50. Coger, V., Million, N., Rehbock, C., Sures, B., Nachev, M., Barcikowski, S., et al. (2019). Tissue concentrations of zinc, iron, copper, and magnesium during the phases of full thickness wound healing in a rodent model. Biological Trace Element Research, 191(1), 167–176. https://doi.org/10.1007/s12011-018-1600-y

    Article  CAS  PubMed  Google Scholar 

  51. Schwartz, J. R., Marsh, R. G., & Draelos, Z. D. (2005). Zinc and skin health: overview of physiology and pharmacology. Dermatologic Surgery, 31, 837–847. https://doi.org/10.1111/j.1524-4725.2005.31729

    Article  CAS  PubMed  Google Scholar 

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Funding

The authors received financial support (Grant No.: SCU.SC.98.20911) from the Shahid Chamran University of Ahvaz.

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Zeinab Ansari-Asl: writing original—draft, conceptualization, methodology, formal analysis, investigation, resources); Soghra Nikpour: conceptualization, methodology, formal analysis, investigation, resources, visualization; Tahereh Sedaghat: conceptualization, methodology, formal analysis, investigation; Elham Hoveizi: writing original—draft, conceptualization, methodology, formal analysis.

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Ansari-Asl, Z., Nikpour, S., Sedaghat, T. et al. Preparation, Characterization, and Wound Healing Assessment of Curcumin-Loaded M-MOF (M = Cu, Zn)@Polycaprolactone Nanocomposite Sponges. Appl Biochem Biotechnol 195, 4308–4320 (2023). https://doi.org/10.1007/s12010-023-04316-0

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