Zinc oxide nanoparticle-reinforced sodium alginate/hydroxyapatite scaffolds for osteoporosis treatment in fragility fracture patients: Development and characterization using artificial neural networks (ANNs) modeling

Document Type : Original Article

Authors

Department of Orthopedics, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu, China

Abstract

Objective(s): Osteoporosis is a significant public health concern due to its association with fragility fractures. Despite experiencing such fractures, many patients remain at high risk of future fractures due to inadequate management and treatment of their underlying osteoporosis. This research presents a comprehensive intervention to enhance osteoporosis management in patients with fragility fractures. The intervention involves a thorough personalized assessment of fracture risk using clinical factors and bone density testing, followed by customized treatment based on the individual’s fracture risk level. It also addresses non-compliance through patient education, counseling, reminders, and improved care coordination among acute, primary, and specialty providers. 
Materials and Methods: The aim is to create and characterize sodium alginate/hydroxyapatite (HA) scaffolds reinforced with zinc oxide nanoparticles (ZnO-NP) for bone tissue engineering. Freeze-drying was used to produce scaffolds with 0–15% ZnO-NP. Analyses confirmed the composite structure, uniform ZnO-NP distribution, and decreasing pore size with higher ZnO-NP content. Mechanical testing showed increased compressive strength with greater ZnO-NP. 
Results: The scaffolds exhibited over 70% porosity, neutral pH, and increased apatite deposition and bioactivity with higher ZnO-NP. They also demonstrated decreased swelling and strong antibacterial activity against Escherichia coli and Staphylococcus aureus, making them a promising candidate for bone regeneration. 
Conclusion: Additionally, the researchers used an artificial neural network (ANN) to better understand the relationships between various scaffold properties, and the ANN-based predictions showed that changes in pore size and porosity affect the other properties, with acceptable error compared to experimental results.

Keywords

Main Subjects

References

1. Salerno A, Oliviero M, Di Maio E, Netti PA, Rofani C, Colosimo A, et al. Design of novel three-phase PCL/TZ–HA biomaterials for use in bone regeneration applications. J Mater Sci Mater Med 2010; 21: 2569-2581.
2. Costa-Pinto AR, Correlo VM, Sol PC, Bhattacharya M, Charbord P, Delorme B, et al. Osteogenic differentiation of human bone marrow mesenchymal stem cells seeded on melt based chitosan scaffolds for bone tissue engineering applications. Biomacromolecules 2009; 10:2067-2073.
3. Butscher A, Bohner M, Hofmann S, Gauckler L, Müller R. Structural and material approaches to bone tissue engineering in powder-based three-dimensional printing. Acta Biomater 2011; 7:907-920.
4. Zhang L, Webster TJ. Nanotechnology and nanomaterials: promises for improved tissue regeneration. Nano Today 2009; 4:66-80.
5. Fatalla AA, Arzani S, Veseli E, Khademi A, Khandan A, Fahmy MD, et al. Revolutionizing systematic reviews and meta-analyses: the role of artificial intelligence in evidence synthesis. Dental Hypotheses 2023; 14:93-94. 
6. Khandan A, Khosravi M, Roustazadeh D, Aghadavoudi F. Impact of alumina and carbon nanotubes on mechanical properties of a composite: molecular dynamic (MD) simulation. Iran J Chemist Chem Eng 2024 (Articles in Press).
7. Moarrefzadeh A, Morovvati M R, Angili S N, Smaisim G F, Khandan A, Toghraie D. Fabrication and finite element simulation of 3D printed poly L-lactic acid scaffolds coated with alginate/carbon nanotubes for bone engineering applications. Int J Biol Macromol 2023; 224:1496-1508.
8. Lee M, Dunn J C, Wu B M. Scaffold fabrication by indirect three-dimensional printing. Biomaterials 2005; 26:4281-4289.
9. Heydary H A, Karamian E, Poorazizi E, Khandan A, Heydaripour J. A novel nano-fiber of Iranian gum tragacanth-polyvinyl alcohol/nanoclay composite for wound healing applications. Proced Mater Sci 2015; 11:176-182.
10. Karamian E, Motamedi M R K, Khandan A, Soltani P, Maghsoudi S. An in vitro evaluation of novel NHA/zircon plasma coating on 316L stainless steel dental implant. Prog Nat Sci Mater Int 2014; 24:150-156.
11. Rahman F F, Bonfield W, Cameron R, Patel M P, Braden M, Pearson G, et al. Water uptake of poly (ethylmethacrylate)/tetrahydrofurfuryl methacrylate polymer systems modified with tricalcium phosphate and hydroxyapatite. Key Eng Mater 2004; 254: 513-516.
12. Wang L, Shelton R M, Cooper P R, Lawson M, Triffitt J T, Barralet J E. Evaluation of sodium alginate for bone marrow cell tissue engineering. Biomaterials 2003; 24:3475-3481.
13. Kanasan N, Adzila S, Mustaffa N A, Sidi S M, Rahman M N A, Nasir N F, et al. The effects of sintering temperature on densification and mechanical properties of hydroxyapatite/sodium alginate biocomposites. MATEC Web Conf 2017; 135:63-71.
14. Rajkumar M, Meenakshisundaram N, Rajendran V. Development of nanocomposites based on hydroxyapatite/sodium alginate: synthesis and characterisation. Mater Charact 2011; 62:469-479.
15. Kanasan N, Adzila S, AzimahMustaffa N, Gurubaran P. The effect of sodium alginate on the properties of hydroxyapatite. Procedia Eng 2017; 184:442-448.
16. Liao J, Li Y, Li H, Liu J, Xie Y, Wang J, et al. Preparation, bioactivity and mechanism of nano-hydroxyapatite/sodium alginate/chitosan bone repair material. J Appl Biomater Funct Mater 2018; 16:28-35.
17. Safaei M M, Abedinzadeh R, Khandan A, Barbaz-Isfahani R, Toghraie D. Synergistic effect of graphene nanosheets and copper oxide nanoparticles on mechanical and thermal properties of composites: experimental and simulation investigations. Mater Sci Eng 2023; 289:116248.
18. Andrade FAC. Desenvolvimento de hidroxiapatita contendo nanopartículas de prata com propriedades antibacterianas. 2013; 119.
19. Chen W, Liu Y, Courtney H S, Bettenga M, Agrawal C M, Bumgardner, et al. In vitro anti-bacterial and biological properties of magnetron co-sputtered silver-containing hydroxyapatite coating. Biomaterials 2016; 27:5512-5517
20. Salmani M M, Hashemian M, Khandan A. Therapeutic effect of magnetic nanoparticles on calcium silicate bioceramic in alternating field for biomedical application. Ceram Int 2020; 46:27299-27307.
21. Mohandas A, Sudheesh Kumar P T, Raja B, Lakshmanan V K, Jayakumar R. Exploration of alginate hydrogel/nano zinc oxide composite bandages for infected wounds. Int J Nanomed 2015; 10:53-66.
22. Khandan A, Jazayeri H, Fahmy M D, Razavi M. Hydrogels: types, structure, properties, and applications. Biomat Tiss Eng 2017; 4:143-169.
23. Zhang R, Ma P X. Poly (α‐hydroxyl acids)/hydroxyapatite porous composites for bone‐tissue engineering. I. Preparation and morphology. J Biomed Mater 1999; 44:446-455.
24.Kokubo T, Takadama H. How useful is SBF in predicting in vivo bone bioactivity?. Biomaterials 2006; 291:2907-2927.
25. Khandan A, Esmaeili S. Fabrication of polycaprolactone and polylactic acid shapeless scaffolds via fused deposition modelling technology. J Adv Mater Process 2019; 7:16-29.
26. Rajaei A, Kazemian M, Khandan A. Investigation of mechanical stability of lithium disilicate ceramic reinforced with titanium nanoparticles. Nanomed Res J 2022; 7:350-359.
27. Zadeh Dadashi M, Kazemian M, Malekipour Esfahani M. Color match of porcelain veneer light-cure resin cements with their respective try-in pastes: chemical stability. Nanochemist Res 2023; 8:205-214.
28. Heydary H A, Karamian E, Poorazizi E, Heydaripour J, Khandan A. Electrospun of polymer/bioceramic nanocomposite as a new soft tissue for biomedical applications. J Asian Ceram Soc 2015; 3:417-425.
29. Lee S, Porter M, Wasko S, Lau G, Chen P Y, Novitskaya E E, et al. Potential bone replacement materials prepared by two methods. MRS-OPL 2012; 1418:.
30. Khandan A, Karamian E, Bonakdarchian M. Mechanochemical synthesis evaluation of nanocrystalline bone-derived bioceramic powder using for bone tissue engineering. Dent Hypotheses 2014; 5:155-161.
31. Ghayour H, Abdellahi M, Ozada N, Jabbrzare S, Khandan A. Hyperthermia application of zinc doped nickel ferrite nanoparticles. J Phys Chem Solids 2017; 111:464-472.
32. Khandan A, Ozada N. Bredigite-magnetite (Ca7MgSi4O16-Fe3O4) nanoparticles: A study on their magnetic properties. J Alloys Compd 2017; 726:729-736.
33. Shayan A, Abdellahi M, Shahmohammadian F, Jabbarzare S, Khandan A, Ghayour H. Mechanochemically aided sintering process for the synthesis of barium ferrite: effect of aluminum substitution on microstructure, magnetic properties and microwave absorption. J Alloys Compd 2017; 708:538-546.
34. Kazemi A, Abdellahi M, Khajeh-Sharafabadi A, Khandan A, Ozada N. Study of in vitro bioactivity and mechanical properties of diopside nano-bioceramic synthesized by a facile method using eggshell as raw material. Mater Sci Eng 2017; 71:604-610.
35. Sharafabadi A K, Abdellahi M, Kazemi A, Khandan A, Ozada N. A novel and economical route for synthesizing akermanite (Ca2MgSi2O7) nano-bioceramic. Mater Sci Eng 2017; 71:1072-1078.
36. Karamian E, Abdellahi M, Khandan A, Abdellah S. Introducing the fluorine doped natural hydroxyapatite-titania nanobiocomposite ceramic. J Alloys Compd 2016; 679:375-383.
37. Khandan A, Abdellahi M, Barenji R V, Ozada N, Karamian E. Introducing natural hydroxyapatite-diopside (NHA-Di) nano-bioceramic coating. Ceram Int 2015; 41:12355-12363.
38. Chen S, Li Y, Zhi S, Ding Z, Huang Y, Wang W, et al. lncRNA xist regulates osteoblast differentiation by sponging miR-19a-3p in aging-induced osteoporosis. Aging Dis 2020; 11:1058–1068. 
39. Zhang Y, Qing L, Luo G, Ahmadpoor X, Li X, Wu P, et al. Variations in deep iliac circumflex artery perforator chimeric flap design for single-stage customized-reconstruction of composite bone and soft-tissue defect. J Plast Reconstr Aesthet Surg 2023; 87:273-283. 
40. Yu Y, Wang L, Ni S, Li D, Liu J, Chu H Y, et al. Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation. Nat Commun 2022; 13:4241-4257. 
41. Song Z H, Xie W, Zhu S Y, Pan J J, Zhou L Y, He C Q. Effects of PEMFs on Osx, Ocn, TRAP, and CTSK gene expression in postmenopausal osteoporosis model mice. Int J Clin Exp Pathol 2018; 11:1784–1790.
42. Zhang Y, Zhao C, Zhang H, Chen M, Meng Y, Pan Y, et al. Association between serum soluble α-klotho and bone mineral density (BMD) in middle-aged and older adults in the United States: a population-based cross-sectional study. Aging Clin Exp Res 2023; 35:2039–2049. 
43. Gai Y, Yin Y, Guan L, Zhang S, Chen J, Yang J, et al. Rational design of bioactive materials for bone hemostasis and defect repair. Cyborg Bionic Syst 2023; 4:58-72. 
44. Bahadori S, Williams J M, Collard S, Swain I. Can a purposeful walk intervention with a distance goal using an activity monitor improve individuals’ daily activity and function post total hip replacement surgery. A randomized pilot trial. Cyborg Bionic Syst 2023; 4:69-82. 
45. Jiang N, Zhang J, Li Z, Zhu S S. Scaffold-based tissue engineering strategies for temporomandibular joint disc regeneration and replacement. Eur Cells Mater 2023; 45:131-142. 
46. Xu Y, Zhang F, Zhai W, Cheng S, Li J, Wang Y, et al. Unraveling of advances in 3D-printed polymer-based bone scaffolds. Polymers 2022; 14:566-597. 
47. Chen Y, Guo Y, Xie B, Jin F, Ma L, Zhang H, et al. Lightweight and drift-free magnetically actuated millirobots via asymmetric laser-induced graphene. Nat Commun 2024; 15:4334-4350. 
48. Zhong Y, Li J, Luo J, Chen F. Advances in bone turnover markers (PINP and CTX) in optimizing anti-resorptive and anabolic therapies against osteoporosis. Discov Med 2021; 32:149-154
49. Kabeer A S, Osmani H T, Patel J, Robinson P, Ahmed N. The adult with low back pain: causes, diagnosis, imaging features and management. Br J Hosp Med 2023; 84:1-9. 
50. Zheng J, Yue R, Yang R, Wu Q, Wu Y, Huang M, et al. Visualization of zika virus infection via a light-initiated bio-orthogonal cycloaddition labeling strategy. Front Bioeng Biotechnol 2022; 1051:1-8. 
51. Mosaddad S A, Hussain A, Tebyaniyan H. Exploring the use of animal models in craniofacial regenerative medicine: a narrative review. Tissue Eng Part B Rev 2024; 30:29-59.
52. Khayatan D, Bagherzadeh Oskouei A, Alam M, Mohammadikhah M, Badkoobeh A, Golkar M, et al. Cross talk between cells and the current bioceramics in bone regeneration: a comprehensive review. Cell Transplant 2024; 33:1-18.
53. Tebyaniyan H, Hussain A, Vivian M. Current antibacterial agents in dental bonding systems: a comprehensive overview. Future Microbiol 2023; 18:825-844.
54. Tahmasebi E, Keshvad A, Alam M, Abbasi K, Rahimi S, Nouri F, et al. Current infections of the orofacial region: treatment, diagnosis, and epidemiology. Life 2023; 13:269-292.
55. Mosaddad S A, Hussain A, Tebyaniyan H. Green alternatives as antimicrobial agents in mitigating periodontal diseases: a narrative review. Microorganisms 2023; 11:1269-1338.
56. Heboyan A, Vardanyan A, Karobari M I, Marya A, Avagyan T, Tebyaniyan H, et al. Dental luting cements: an updated comprehensive review. Molecules 2023; 28:1619-1635.
57. Yazdanian M, Alam M, Abbasi K, Rahbar M, Farjood A, Tahmasebi E, et al. Synthetic materials in craniofacial regenerative medicine: a comprehensive overview. Front Bioeng Biotechnol 2022; 10: 1-24.
58. Hussain A, Tebyaniyan H, Khayatan D. The role of epigenetic in dental and oral regenerative medicine by different types of dental stem cells: a comprehensive overview. Stem Cells Int 2022; 2022:1-15.
59. Barzegar P E F, Ranjbar R, Yazdanian M, Tahmasebi E, Alam M, Abbasi K, et al. The current natural/chemical materials and innovative technologies in periodontal diseases therapy and regeneration: A narrative review. Mater Today Commun 2022; 32:104099.
60. Yazdanian M, Rahmani A, Tahmasebi E, Tebyanian H, Yazdanian A, Mosaddad S A. Current and advanced nanomaterials in dentistry as regeneration agents: an update. Mini Rev Med Chem 2021; 21:899-918.
61. Yazdanian M, Arefi A H, Alam M, Abbasi K, Tebyaniyan H, Tahmasebi E, et al. Decellularized and biological scaffolds in dental and craniofacial tissue engineering: a comprehensive overview. J Mater Res Technol 2021; 15:1217-1251.
62. Moghadam ET, Yazdanian M, Alam M, Tebyanian H, Tafazoli A, Tahmasebi E, et al. Current natural bioactive materials in bone and tooth regeneration in dentistry: a comprehensive overview. J Mater Res Technol 2021; 13:2078-2114.
63. Soudi A, Yazdanian M, Ranjbar R, Tebyanian H, Yazdanian A, Tahmasebi E, et al. Role and application of stem cells in dental regeneration: a comprehensive overview. EXCLI J 2021; 20:454-489.
64. Hakim L K, Yazdanian M, Alam M, Abbasi K, Tebyaniyan H, Tahmasebi E, et al. Biocompatible and biomaterials application in drug delivery system in oral cavity. Evid Based Complement Alternat Med 2021; 2021:1-12.
65. Yazdanian M, Tabesh H, Houshmand B, Tebyanian H, Soufdoost R S, Tahmasebi E, et al. Fabrication and properties of βTCP/Zeolite/Gelatin scaffold as developed scaffold in bone regeneration: in vitro and in vivo studies. Biocybern Biomed Eng 2020; 40:1626-1637.
66. Tahmasebi E, Alam M, Yazdanian M, Tebyanian H, Yazdanian A, Seifalian A, et al. Current biocompatible materials in oral regeneration: a comprehensive overview of composite materials. J Mater Res Technol 2020; 9:11731-11755.
67. Mosaddad S A, Yazdanian M, Tebyanian H, Tahmasebi E, Yazdanian A, Seifalian A, et al. Fabrication and properties of developed collagen/strontium-doped bioglass scaffolds for bone tissue engineering. J Mater Res Technol 2020; 9:14799-14817.
68. Soufdoost R S, Yazdanian M, Tahmasebi E, Yazdanian A, Tebyanian H, Karami A, et al. In vitro and in vivo evaluation of novel tadalafil/β-TCP/collagen scaffold for bone regeneration: a rabbit critical-size calvarial defect study. Biocybern Biomed Eng 2019; 39:789-796.
69. Hussein H A M, Al-Judy H J. Effect of incorporation of boron nitride nanoparticles on impact strength and surface roughness of heat cure poly methyl methacrylate resin: an in vitro study. Dent Hypotheses 2023; 14:19-21.
70. Kamarian, S., Barbaz-Isfahani, R., Tran, T. M. N., & Song, J. I. Optimal flammability and thermal buckling resistance of eco-friendly abaca fiber/polypropylene/egg shell powder/halloysite nanotubes composites. 2024; Adv Nano Res 16: 127.
71. Alimirzaei S, Barbaz-Isfahani R, Khodaei A, Najafabadi M A, Sadighi M. Investigating the flexural behavior of nanomodified multi-delaminated composites using acoustic emission technique. Ultrasonics 2024; 138:107249.
72. Kamarian S, Bodaghi M, Isfahani R B, Song J I. A comparison between the effects of shape memory alloys and carbon nanotubes on the thermal buckling of laminated composite beams. Mech Based Des Struct Mach 2022; 50:2250-2273.
73. Turki O H, Jafar Z J. Antibacterial activity of Juglans regia L. dry husk extract against Streptococcus mutans and Lactobacillus: an in vitro study. Dent Hypotheses 2023; 14:29-31.
74. Hasan Z R, Al-Hasani N R, Mahmood M A, Ibrahim A I. Effect of amoxicillin and azithromycin suspensions on microhardness of sliver reinforced and nano resin-modified glass ionomers: an in vitro study. Dent Hypotheses 2023; 14:32-35.
 
Iranian Journal of Basic Medical Sciences
Volume 27, Issue 12
December 2024
Pages 1592-1603

Files

Share

How to cite

Statistics