Hydrogel nanocomposite based on alginate/zeolite for burn wound healing: In vitro and in vivo study

Document Type : Original Article

Authors

1 Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

2 Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran

3 Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

4 Sexual Health and Fertility Research center, Shahroud University of Medical Sciences, Shahroud, Iran

5 Tissue Engineering and Stem Cells Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

6 Department of Microbiology and Virology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

7 Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran

8 Department of Hematology and Laboratory Sciences, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran

9 Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

10 Radiation Biology Research Center Iran University of Medical Sciences (IUMS) Tehran, Iran

11 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

12 Department of Medical Nanotechnology, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Objective(s): The main objective of the current assay was to evaluate the antibacterial and regenerative effects of hydrogel nanocomposite containing pure natural zeolite (clinoptilolite) integrated with alginate (Alg) as wound healing/dressing biomaterials.
Materials and Methods: The zeolites were size excluded, characterized by SEM, DLS, XRD, FTIR, and XRF, and then integrated into Alg hydrogel followed by calcium chloride crosslinking. The Alg and alginate zeolite (Alg/Zeo) hydrogel was characterized by swelling and weight loss tests, also the antibacterial, hemocompatibility, and cell viability tests were performed. In animal studies, the burn wound was induced on the back of rats and treated with the following groups: control, Alg hydrogel, and Alg/Zeo hydrogel.
Results: The results showed that the hydrodynamic diameter of zeolites was 367 ± 0.2 nm. Zeolites did not show any significant antibacterial effect, however, the hydrogel nanocomposite containing zeolite had proper swelling as well as hemocompatibility and no cytotoxicity was observed. Following the creation of a third-degree burn wound on the back of rats, the results indicated that the Alg hydrogel and Alg/Zeo nanocomposite accelerated the wound healing process compared with the control group. Re-epithelialization, granulation tissue thickness, collagenization, inflammatory cell recruitment, and angiogenesis level were not significantly different between Alg and Alg/Zeo nanocomposite.
Conclusion: These findings revealed that although the incorporation of zeolites did not induce a significant beneficial effect in comparison with Alg hydrogel, using zeolite capacity in hydrogel for loading the antibiotics or other effective compounds can be considered a promising wound dressing.

Keywords

Main Subjects


1. Shah SA, Sohail M, Khan S, Minhas MU, De Matas M, Sikstone V, et al. Biopolymer-based biomaterials for accelerated diabetic wound healing: a critical review. Int J Biol Macromol 2019; 139:975-993.
2.    Davison-Kotler E, Marshall WS, García-Gareta E. Sources of collagen for biomaterials in skin wound healing. Bioengineering 2019; 6:56-71.
3.    Bianchera A, Catanzano O, Boateng J, Elviri L. The place of biomaterials in wound healing. Ther Dress Wound Heal Appl 2020; 2020:337-366.
4.    Pourshahrestani S, Zeimaran E, Kadri NA, Mutlu N, Boccaccini AR. Polymeric hydrogel systems as emerging biomaterial platforms to enable hemostasis and wound healing. Adv Healthc Mater 2020; 9:1-52.
5.    Ding C, Tian M, Feng R, Dang Y, Zhang M. Novel self-healing hydrogel with injectable, pH-responsive, strain-sensitive, promoting wound-healing, and hemostatic properties based on collagen and chitosan. ACS Biomater Sci Eng 2020; 6:3855-3867.
6.    Salehi M, Zamiri S, Samadian H, Ai J, Foroutani L, Ai A, et al. Chitosan hydrogel loaded with aloe vera gel and tetrasodium ethylenediaminetetraacetic acid (EDTA) as the wound healing material: in vitro and in vivo study. J Appl Polym Sci 2021; 138:50225-50235.
7.    Samadian H, Khastar H, Ehterami A, Salehi M. Bioengineered 3D nanocomposite based on gold nanoparticles and gelatin nanofibers for bone regeneration: in vitro and in vivo study. Sci Rep 2021; 11:1-11.
8.    Murray RZ, West ZE, Cowin AJ, Farrugia BL. Development and use of biomaterials as wound healing therapies. Burns Trauma 2019; 7:2-20.
9.    Nazarnezhada S, Abbaszadeh-Goudarzi G, Samadian H, Khaksari M, Ghatar JM, Khastar H, et al. Alginate hydrogel containing hydrogen sulfide as the functional wound dressing material: in vitro and in vivo study. Int J Biol Macromol 2020; 164:3323-3331.
10.    Mohammadpour M, Samadian H, Moradi N, Izadi Z, Eftekhari M, Hamidi M, et al. Fabrication and characterization of nanocomposite hydrogel based on alginate/nano-hydroxyapatite loaded with linum usitatissimum extract as a bone tissue engineering scaffold. Mar Drugs 2022; 20:20-38.
11.    Kurakula M, Rao GK, Kiran V, Hasnain MS, Nayak AK. Alginate-based hydrogel systems for drug releasing in wound healing.  Alginates Drug Deliv 2020; :323-358.
12.    Liao J, Jia Y, Wang B, Shi K, Qian Z. Injectable hybrid poly (ε-caprolactone)-b-poly (ethylene glycol)-b-poly (ε-caprolactone) porous microspheres/alginate hydrogel cross-linked by calcium gluconate crystals deposited in the pores of microspheres improved skin wound healing. ACS Biomater Sci Eng 2018; 4:1029-1036.
13.    Thomas A, Harding K, Moore K. Alginates from wound dressings activate human macrophages to secrete tumour necrosis factor-α. Biomaterials 2000; 21:1797-1802.
14.    Yang D, Jones KS. Effect of alginate on innate immune activation of macrophages. J Biomed Mater Res A 2009; 90:411-418.
15.    Ninan N, Muthiah M, Park I-K, Wong TW, Thomas S, Grohens Y. Natural polymer/inorganic material based hybrid scaffolds for skin wound healing. Polym Rev 2015; 55:453-490.
16.    Iqbal N, Kadir MRA, Mahmood NHB, Yusoff MFM, Siddique JA, Salim N, et al. Microwave synthesis, characterization, bioactivity and in vitro biocompatibility of zeolite–hydroxyapatite (Zeo–HA) composite for bone tissue engineering applications. Ceram Int 2014; 40:16091-16097.
17.    McDonnell AM, Beving D, Wang A, Chen W, Yan Y. Hydrophilic and antimicrobial zeolite coatings for gravity‐independent water separation. Adv Func Mater 2005; 15:336-340.
18.    Tondar M, Parsa MJ, Yousefpour Y, Sharifi AM, Shetab-Boushehri SV. Feasibility of clinoptilolite application as a microporous carrier for pH-controlled oral delivery of aspirin. Acta Chimica Slovenica 2014; 61:688-693.
19.    Hovhannisyan VA, Dong C-Y, Lai F-J, Chang N-S, Chen S-J. Natural zeolite for adsorbing and release of functional materials. J Biomed Opt 2018; 23:1-7.
20.    Demirci S, Ustaoğlu Z, Yılmazer GA, Sahin F, Baç N. Antimicrobial properties of zeolite-X and zeolite-A ion-exchanged with silver, copper, and zinc against a broad range of microorganisms. Appl Biochem Biotechnol 2014; 172:1652-1662.
21.    Concepción-Rosabal B, Rodríguez-Fuentes G, Bogdanchikova N, Bosch P, Avalos M, Lara V. Comparative study of natural and synthetic clinoptilolites containing silver in different states. Microporous Mesoporous Mater 2005; 86:249-255.
22.    Cerri G, Farina M, Brundu A, Daković A, Giunchedi P, Gavini E, et al. Natural zeolites for pharmaceutical formulations: preparation and evaluation of a clinoptilolite-based material. Microporous Mesoporous Mater 2016; 223:58-67.
23.    Koyama K, Takeuchi Y. Clinoptilolite: the distribution of potassium atoms and its role in thermal stability. Zeitschrift für Kristallographie-Crystalline Materials 1977; 145:216-239.
24.    Zhang M, Sun L, Wang X, Chen S, Kong Y, Liu N, et al. Activin B promotes BMSC-mediated cutaneous wound healing by regulating cell migration via the JNK—ERK signaling pathway. Cell Transplant 2014; 23:1061-1073.
25.    Baghbanian SM, Rezaei N, Tashakkorian H. Nanozeolite clinoptilolite as a highly efficient heterogeneous catalyst for the synthesis of various 2-amino-4 H-chromene derivatives in aqueous media. Green Chemist 2013; 15:3446-3458.
26.    Treacy MM, Higgins JB. Collection of simulated XRD powder patterns for zeolites fifth (5th) revised edition: Elsevier; 2007.
27.    Olad A, Doustdar F, Gharekhani H. Starch-based semi-IPN hydrogel nanocomposite integrated with clinoptilolite: preparation and swelling kinetic study. Carbohydr polym 2018; 200:516-528.
28.    Dinu MV, Lazar MM, Dragan ES. Dual ionic cross-linked alginate/clinoptilolite composite microbeads with improved stability and enhanced sorption properties for methylene blue. React Funct Polym 2017; 116:31-40.
29.    Rashidzadeh A, Olad A, Salari D. The effective removal of methylene blue dye from aqueous solutions by NaAlg-g-poly (acrylic acid-co-acryl amide)/clinoptilolite hydrogel nanocomposite. Fibers Polym 2015; 16:354-362.
30.    Khalid I, Ahmad M, Minhas MU, Barkat K. Preparation and characterization of alginate-PVA-based semi-IPN: controlled release pH-responsive composites. Polym Bull 2018; 75:1075-1099.
31.    Iqbal B, Muhammad N, Jamal A, Ahmad P, Khan ZUH, Rahim A, et al. An application of ionic liquid for preparation of homogeneous collagen and alginate hydrogels for skin dressing. J Mol Liq 2017; 243:720-725.
32.    Manjula B, Varaprasad K, Sadiku R, Raju KM. Preparation and characterization of sodium alginate–based hydrogels and their in vitro release studies. Adv Polym Technol 2013; 32:1-12.
33.    Kobayashi I, Muraoka H, Saika T, Nishida M, Fujioka T, Nasu M. Micro-broth dilution method with air-dried microplate for determining MICs of clarithromycin and amoxycillin for Helicobacter pylori isolates. J Med Microbiol 2004; 53:403-406.
34.    Liang Y, Xu C, Liu F, Du S, Li G, Wang X. Eliminating heat injury of zeolite in hemostasis via thermal conductivity of graphene sponge. ACS Appl Mater Interfaces 2019; 11:23848-23857.
35.    Sang Y, Li W, Liu H, Zhang L, Wang H, Liu Z, et al. Construction of nanozyme‐hydrogel for enhanced capture and elimination of bacteria. Adv Funct Mater 2019; 29:1900518-1900528.
36.    Taaca KLM, Olegario EM, Vasquez MR. Impregnation of silver in zeolite–chitosan composite: thermal stability and sterility study. Clay Miner 2019; 54:145-151.
37.    Tavakolian M, Munguia-Lopez JG, Valiei A, Islam MS, Kinsella JM, et al. Highly absorbent antibacterial and biofilm-disrupting hydrogels from cellulose for wound dressing applications. ACS Appl Mater Interfaces 2020; 12:39991-40001.
38.    Fan Z, Liu B, Wang J, Zhang S, Lin Q, Gong P, et al. A novel wound dressing based on Ag/graphene polymer hydrogel: effectively kill bacteria and accelerate wound healing. Adv Funct Mater 2014; 24:3933-3943.
39.    Hubner P, Donati N, de Menezes Quines LK, Tessaro IC, Marcilio NR. Gelatin-based films containing clinoptilolite-Ag for application as wound dressing. Mater Sci Eng C 2020; 107:110215-110230.
40. Karoyo AH, Wilson LD. A review on the design and hydration properties of natural polymer-based hydrogels. Materials 2021; 14:1095-1130.
41. Ahmed EM. Hydrogel: preparation, characterization, and applications: a review. J Adv Res 2015; 6:105-1021.
42. Mahon R, Balogun Y, Oluyemi G, Njuguna J. Swelling performance of sodium polyacrylate and poly (acrylamide-co-acrylic acid) potassium salt. SN Appl Sci 2020; 2:1-15.
43.    Zhang J, Wang Q, Wang A. In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices. Acta Biomater 2010; 6:445-454.
44.    Fan L, Zhang J, Wang A. In situ generation of sodium alginate/hydroxyapatite/halloysite nanotubes nanocomposite hydrogel beads as drug-controlled release matrices. J Mater Chem B 2013; 1:6261-6270.
45.    Bajpai S, Sharma S. Investigation of swelling/degradation behaviour of alginate beads crosslinked with Ca2+ and Ba2+ ions. React Funct Polym 2004; 59:129-140.
46.    Milyovich S, Pantyo V, Danko E, Pogodin A, Filep M, Fizer O, et al. Antibacterial application of carpathian clinoptilolite as cetylpyridinium carrier. 2022; .
47.    Ninan N, Muthiah M, Yahaya NAB, Park I-K, Elain A, Wong TW, et al. Antibacterial and wound healing analysis of gelatin/zeolite scaffolds. Colloids Surf B 2014; 115:244-252.
48.    de Gennaro B, Catalanotti L, Cappelletti P, Langella A, Mercurio M, Serri C, et al. Surface modified natural zeolite as a carrier for sustained diclofenac release: a preliminary feasibility study. Colloids Surf B 2015; 130:101-109.
49.    Taaca KLM, Vasquez Jr MR. Fabrication of ag-exchanged zeolite/chitosan composites and effects of plasma treatment. Microporous Mesoporous Mater 2017; 241:383-391.
50.    Montallana ADS, Cruz CEV, Vasquez Jr MR. Antibacterial activity of copper-loaded plasma-treated natural zeolites. Plasma Med 2018; 8:1-10.
51.    Serati-Nouri H, Jafari A, Roshangar L, Dadashpour M, Pilehvar-Soltanahmadi Y, Zarghami N. Biomedical applications of zeolite-based materials: a review. Mater Sci Eng C 2020; 116:111225-111238.
52.    Kocaaga B, Kurkcuoglu O, Tatlier M, Batirel S, Guner FS. Low‐methoxyl pectin–zeolite hydrogels controlling drug release promote in vitro wound healing. J Appl Polym Sci 2019; 136:47640-47656.
53. Bacakova L, Vandrovcova M, Kopova I, Jirka I. Applications of zeolites in biotechnology and medicine–a review. Biomater Sci 2018; 6:974-989.
54. Salehi H, Mehrasa M, Nasri-Nasrabadi B, Doostmohammadi M, Seyedebrahimi R, Davari N, et al. Effects of nanozeolite/starch thermoplastic hydrogels on wound healing. J Res Med Sci 2017; 22:110-119.