ANTIOXIDANT PROPERTIES OF OSTEOGENIC APATITE-POLYMER BIOMATERIALS FUNCTIONALIZED WITH PHYTOCOMPOUNDS
Abstract
Background. Innovative methods of regenerating damaged bone involve the use of new materials with incorporated biologically active molecules, stem cells, carbon and metal nanoparticles. Ceramics based on calcium orthophosphates are an alternative to native bone tissue, and their modification with nanoparticles (NPs) to improve the properties and functionality of composites is a new trend in the science of biomaterials. The known toxic effect of NPs on the human body by provoking oxidative stress through the formation of reactive oxygen species (ROS), an excessive amount of which causes DNA damage and death of surrounding cells requires the search for effective antioxidants for biomaterials.
Materials and Methods. The study was conducted to review the literature on the use of biologically active compounds of plant origin, characterized by high antioxidant activity and osteoconductive properties, in biomedical engineering.
Results. To accelerate implant osseointegration, it is important to protect bone cells from oxidative stress, which increases inflammation and can lead to implant rejection. The use of antioxidants, namely polyphenolic compounds, can improve the biocompatibility of biomaterials and increase their antioxidant properties. The review provides data on the use of such biologically active phytocompounds as extracts of medicinal plants (Fructus chebulae, Aloe vera, Camelia sinensis, Salvia officinalis), naringin, quercetin, kaempferol, resveratrol, catechins. By functionalizing biomaterials, the appropriate concentration of bioactive compounds in the implantation zone is maintained, and their release is controlled, which contributes to the neutralization of ROS, the proliferation and osteogenic differentiation of cells with osteogenic potential, the activity of osteoclasts is suppressed, and various signaling pathways are regulated.
Conclusions. The analysis of literature sources has shown that polyphenolic compounds are promising phytocompounds used in the synthesis of innovative osteogenic biocomposite materials. The combination of polyphenols with various materials improves the biocompatibility, antioxidant properties, osteoconductivity and osteoinductivity of biomaterials. The ability of plant polyphenols to reduce inflammation and promote tissue regeneration, including bone, makes them promising compounds in biomolecular engineering.
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Bădilă A. E., Rădulescu D. M., Ilie A., Niculescu A. G., Grumezescu A. M., Rădulescu A. R. Bone Regeneration and Oxidative Stress: An Updated Overview. Antioxidants. 2022;11:318. https://doi.org/10.3390/antiox11020318
Qin D., Zhang H., Zhang H., Sun T., Zhao H., Lee W. H. Anti-osteoporosis effects of osteoking via reducing reactive oxygen species. Journal of ethnopharmacology. 2019;244: 112045. https://doi.org/10.1016/j.jep.2019.112045
Agidigbi T. S., Kim C. Reactive oxygen species in osteoclast differentiation and possible pharmaceutical targets of ROS-mediated osteoclast diseases. International Journal of Molecular Sciences. 2019;20(14):3576. https://doi.org/10.3390/ijms20143576
Nattagh‐Eshtivani E., Gheflati A., Barghchi H., Rahbarinejad P., Hachem K., Shalaby M. N., Pahlavani N. The role of Pycnogenol in the control of inflammation and oxidative stress in chronic diseases: Molecular aspects. Phytotherapy Research. 2022;36(6):23522374. https://doi.org/10.1002/ptr.7454
Cerqueni G., Scalzone A., Licini C., Gentile P., Mattioli-Belmonte M. Insights into oxidative stress in bone tissue and novel challenges for biomaterials. Materials Science and Engineering. 2021;130:112433. https://doi.org/10.1016/j.msec.2021.112433
Farahi H., Mashhadi-Rafie S., Jahandideh A., Asghari A., Shirazi-Beheshtiha S. H. Evaluation of possible beneficial effect of tricalcium phosphate/collagen (TCP/Collagen) nanocomposite scaffold on bone healing in rabbits: biochemical assessments. Iranian Journal of Veterinary Surgery. 2019;14(2):162-172. https://doi.org/10.22034/ivsa.2019.193769.1189
Shao M., Bigham A., Yousefiasl S., Yiu C. K., Girish Y. R., Ghomi M., Wu A. Recapitulating antioxidant and antibacterial compounds into a package for tissue regeneration: dual function materials with synergistic effect. Small. 2023;19:2207057. https://doi.org/10.1002/smll.202207057
Shi G., Yang C., Wang Q., Wang S., Wang G., Ao R., Li D. Traditional Chinese medicine compound-loaded materials in bone regeneration. Frontiers in bioengineering and biotechnology. 2022;10:851561. https://doi.org/10.3389/fbioe.2022.851561
Żukowski P., Maciejczyk M., Waszkiel D. Sources of free radicals and oxidative stress in the oral cavity. Archives of Oral Biology. 2018;92:8-17. https://doi.org/10.1016/j.archoralbio.2018.04.018
Marcucci G., Domazetovic V., Nediani C., Ruzzolini J., Favre C., Brandi M. L. Oxidative stress and natural antioxidants in osteoporosis: Novel preventive and therapeutic approaches. Antioxidants. 2023;12(2):373. https://doi.org/10.3390/antiox12020373
Han C., Guo M., Bai J., Zhao L., Wang L., Song W., Zhang P. Quercetin-loaded nanocomposite microspheres for chronologically promoting bone repair via synergistic immunoregulation and osteogenesis. Materials & Design. 2022;222:111045. https://doi.org/10.1016/j.matdes.2022.111045
Li M., Wei F., Yin X., Xiao L., Yang L., Su J., Zhou Y. Synergistic regulation of osteoimmune microenvironment by IL-4 and RGD to accelerate osteogenesis. Materials Science and Engineering. 2020;109:110508. https://doi.org/10.1016/j.msec.2019.110508
Fu M., Li J., Liu M., Yang C., Wang Q., Wang H., Sun G. Sericin/Nano-Hydroxyapatite Hydrogels Based on Graphene Oxide for Effective Bone Regeneration via Immunomodulation and Osteoinduction. International Journal of Nanomedicine. 2023;18:1875-1895. https://doi.org/10.2147/IJN.S399487
Xue H., Zhang Z., Lin Z., Su J., Panayi A. C., Xiong Y., Liu G. Enhanced tissue regeneration through immunomodulation of angiogenesis and osteogenesis with a multifaceted nanohybrid modified bioactive scaffold. Bioactive materials. 2022;18:552-568. https://doi.org/10.1016/j.bioactmat.2022.05.023
Kasote D.M., Katyare S.S., Hedge M.V., Bae H. Significance of antioxidant potential of plants and its relevance to therapeutic applications. International Journal of Biological Sciences. 2015;11(8):982-991. https://doi.org/10.7150/ijbs.12096
Gonçalves A.M., Moreira A., Weber A., Williams G.R., Costa P.F. Osteochondral Tissue Engineering: The Potential of Electrospinning and Additive Manufacturing. Pharmaceutics. 2021;13:983. https://doi.org/10.3390/pharmaceutics13070983
Fendi F., Abdullah B., Suryani S., Usman A. N., Tahir D. Development and application of hydroxyapatite-based scaffolds for bone tissue regeneration: A systematic literature review. Bone. 2024;183:117075. https://doi.org/10.1016/j.bone.2024.117075
Nasar A. Hydroxyapatite and its coatings in dental implants. [Applications of Nanocomposite Materials in Dentistry]. 2019;145-160. Woodhead Publishing. https://doi.org/10.1016/B978-0-12-813742-0.00008-0
Bai Y., Kanno T., Tatsumi H., Miyamoto K., Sha J., Hideshima K., Matsuzaki Y. Feasibility of a three-dimensional porous uncalcined and unsintered hydroxyapatite/poly-d/l-lactide composite as a regenerative biomaterial in maxillofacial surgery. Materials. 2018;11(10):2047. https://doi.org/10.3390/ma11102047
Siddiqui H.A., Pickering K.L., Mucalo M.R. A review on the use of hydroxyapatite-carbonaceous structure composites in bone replacement materials for strengthening purposes. Materials. 2018;11(10):1813. https://doi.org/10.3390/ma11101813
Cerqueni G., Scalzone A., Licini C., Gentile P., Mattioli-Belmonte M. Insights into oxidative stress in bone tissue and novel challenges for biomaterials. Materials Science and Engineering: C. 2021;130:112433. https://doi.org/10.3390/antiox11020318
Raja I.S., Preeth D.R., Vedhanayagam M., Hyon S., Lim D., Kim B., Rajalakshmi S., Han D.W. Polyphenols-loaded electrospun nanofibers in bone tissue engineering and regeneration. Biomaterial Research. 2021;25:29. https://doi.org/10.1186/s40824-021-00229-3
Zhao Y., Sun Z. Effects of gelatin-polyphenol and gelatin–genipin cross-linking on the structure of gelatin hydrogels. International Journal of Food Properties. 2017;20(3):S2822-S2832. https://doi.org/10.1080/10942912.2017.1381111
Zhao X., Pei D., Yang Y., Xu K., Yu J., Zhang Y., Zhang Q., He G., Zhang Y., Li A., Cheng Y., Chen X. Green tea derivative driven smart hydrogels with desired functions for chronic diabetic wound treatment. Advanced functional materials. 2021;31(18):2009442. https://doi.org/10.1002/adfm.202009442
Słota D., Florkiewicz W., Piętak K., Szwed A., Włodarczyk M., Siwińska M., Rudnicka K., Sobczak-Kupiec A. Preparation, Characterization, and Biocompatibility Assessment of Polymer-Ceramic Composites Loaded with Salvia officinalis Extract. Materials. 2021;14:6000. https://doi.org/10.3390/ma14206000
Garcia C. F., Marangon C. A., Massimino L. C., Klingbeil M. F. G., Martins V. C. A., de Guzzi Plepis A. M. Development of collagen/nanohydroxyapatite scaffolds containing plant extract intended for bone regeneration. Materials Science and Engineering: C. 2021;123:111955. https://doi.org/10.1016/j.msec.2021.111955
Zhu Y., Zhou D., Zan X., Ye Q., Sheng S. Engineering the surfaces of orthopedic implants with osteogenesis and antioxidants to enhance bone formation in vitro and in vivo. Colloids and Surfaces B: Biointerfaces. 2022;212:112319. https://doi.org/10.1016/j.colsurfb.2022.112319
Hashemi S.A., Madani S.A., Abediankenari S. The Review on Properties of Aloe Vera in Healing of Cutaneous Wounds. BioMed Research International. 2015;2015:14216. https://doi.org/10.1155/2015/714216
Usman M., Alam M. Aloe vera: A Multipurpose Plant, A review. International Journal of Chemical and Biochemical Sciences. 2024;25(13):536-550.
Hęś M., Dziedzic K., Górecka D., Jędrusek-Golińska A., Gujska E. Aloe vera (L.) Webb.: natural sources of antioxidants–a review. Plant Foods for Human Nutrition. 2019;74:255-265. https://doi.org/10.1007/s11130-019-00747-5
Yoshida C. M., Pacheco M. S., de Moraes M. A., Lopes P. S., Severino P., Souto E. B., da Silva C. F. Effect of chitosan and Aloe vera extract concentrations on the physicochemical properties of chitosan biofilms. Polymers. 2021;13(8):1187. https://doi.org/10.3390/polym13081187
Isfandiary A., Widiyanti P., Hikmawati D. Composite of chitosan-collagen-aloe vera for scaffolds application on skin tissue. Journal of Biomimetics, Biomaterials and Biomedical Engineering. 2017;32:82-89. https://doi.org/10.4028/www.scientific.net/JBBBE.32.82
Garcia-Orue I., Gainza G., Gutierrez F. B., Aguirre J. J., Evora C., Pedraz J. L., Igartua M. Novel nanofibrous dressings containing rhEGF and Aloe vera for wound healing applications. International journal of pharmaceutics. 2017;523(2):556-566. https://doi.org/10.1016/j.ijpharm.2016.11.006
Shanmugavel S., Reddy V. J., Ramakrishna S., Lakshmi B. S., Dev V. G. Precipitation of hydroxyapatite on electrospun polycaprolactone/aloe vera/silk fibroin nanofibrous scaffolds for bone tissue engineering. Journal of Biomaterials Applications. 2013;29(1):46-58. https://doi.org/10.1177/0885328213513934
Tasomara R., Herdianto N., Gustiono D., Rahmania A.W., Hakim H., Lukmana. Characterization of Mesoporous Biphasic Calcium Phosphate Synthesized Using Chitosan and Aloe Vera Template. MSF. 2021;1028:339–45. https://doi.org/10.4028/www.scientific.net/msf.1028.339
Lesjak M., Beara I., Simin N., Pintac D., Majkic T., Bekvalac K., Orcic D., Mimica-Dukic N. Antioxidant and anti-inflammatory activities of quercetin and its derivatives. Journal of Functional Foods. 2018;40:68-75. https://doi.org/10.1016/j.jff.2017.10.047
Wong S. K., Chin K. Y., Ima-Nirwana S. Quercetin as an agent for protecting the bone: a review of the current evidence. International journal of molecular sciences. 2020;21(17):6448. https://doi.org/10.3390/ijms21176448
Wang N., Wang L., Yang J., Wang Z., Cheng L. Quercetin promotes osteogenic differentiation and antioxidant responses of mouse bone mesenchymal stem cells through activation of the AMPK/SIRT1 signaling pathway. Phytotherapy Research. 2021;35(5):2639-2650. https://doi.org/10.1002/ptr.7010
Oh J. H., Karadeniz F., Seo Y., Kong C. S. Effect of quercetin 3-O-β-D-galactopyranoside on the adipogenic and osteoblastogenic differentiation of human bone marrow-derived mesenchymal stromal cells. International journal of molecular sciences. 2020;21(21):8044. https://doi.org/10.3390/ijms21218044
Sohrabi M., Hesaraki S., Shahrezaee M., Shams-Khorasani A., Roshanfar F., Glasmacher B., Makvandi P. Antioxidant flavonoid-loaded nano-bioactive glass bone paste: in vitro apatite formation and flow behavior. Nanoscale Advances. 2024;6(3):1011-1022. https://doi.org/10.1039/D3NA00941F
Han C., Guo M., Bai J., Zhao L., Wang L., Song W., Zhang P. Quercetin-loaded nanocomposite microspheres for chronologically promoting bone repair via synergistic immunoregulation and osteogenesis. Materials & Design. 2022;222:111045. https://doi.org/10.1016/j.matdes.2022.111045
Forte L., Torricelli P., Boanini E., Gazzano M., Rubini K., Fini M., Bigi A. Antioxidant and bone repair properties of quercetin-functionalized hydroxyapatite: An in vitro osteoblast-osteoclast-endothelial cell co-culture study. Acta biomaterialia. 2016;32:298-308. https://doi.org/10.1016/j.actbio.2015.12.013
Azeem M., Hanif M., Mahmood K., Ameer N., Chughtai F. R. S., Abid U. An insight into anticancer, antioxidant, antimicrobial, antidiabetic and anti-inflammatory effects of quercetin: A review. Polymer Bulletin. 2023;80(1):241-262. https://doi.org/10.1007/s00289-022-04091-8
Wong S. K., Chin K. Y., Ima-Nirwana S. Quercetin as an agent for protecting the bone: a review of the current evidence. International journal of molecular sciences. 2020;21(17):6448. https://doi.org/10.3390/ijms21176448
Forte L., Torricelli P., Boanini E., Rubini K., Fini M., Bigi A. Quercetin and alendronate multi‐functionalized materials as tools to hinder oxidative stress damage. Journal of Biomedical Materials Research Part A. 2017;105(12):3293-3303.https://doi.org/10.1002/jbm.a.36192
Sukhodub, L., Bozhko, N., Kumeda, M., Sukhodub, L. Antioxidant Potential of Quercetin and Rosemary Extract as Components of Nanometric Apatite Biopolymer Materials for Osteoplasty. 2024;http://dx.doi.org/10.2139/ssrn.4793147
47.Gillman C. E., Jayasuriya A. C. FDA-approved bone grafts and bone graft substitute devices in bone regeneration. Materials Science and Engineering: C. 2021;130:112466. https://doi.org/10.1016/j.msec.2021.112466
Marrazzo P., O’Leary C. Repositioning Natural Antioxidants for Therapeutic Applications in Tissue Engineering. Bioengineering. 2020;7:104. https://doi.org/10.3390/bioengineering7030104
Checinska K., Checinski M., Cholewa-Kowalska K., Sikora M., Chlubek D. Polyphenol-Enriched Composite Bone Regeneration Materials: A Systematic Review of In Vitro Studies. International Journal Molecular Science. 2022;23:7473. https://doi.org/10.3390/ijms23137473
Zuo Y., Li Q., Xiong Q., Li J., Tang C., Zhang Y., Wang D. Naringin release from a nano-hydroxyapatite/collagen scaffold promotes osteogenesis and bone tissue reconstruction. Polymers. 2022;14(16):3260. https://doi.org/10.3390/polym14163260
Zhao Z. H., Ma X. L., Zhao B., Tian P., Ma J. X., Kang J. Y., Sun L. Naringin‐inlaid silk fibroin/hydroxyapatite scaffold enhances human umbilical cord‐derived mesenchymal stem cell‐based bone regeneration. Cell Proliferation. 2021;54(7):e13043. https://doi.org/10.1111/cpr.13043
Guo Z., Bo D., He P., Li H., Wu G., Li Z., Li Q. Sequential controlled-released dual-drug loaded scaffold for guided bone regeneration in a rat fenestration defect model. Journal of materials chemistry B. 2017;5(37):7701-7710. https://doi.org/10.1039/c7tb00909g
Guo Z., Wu S., Li H., Li Q., Wu G., Zhou C. In vitro evaluation of electrospun PLGA/PLLA/PDLLA blend fibers loaded with naringin for guided bone regeneration. Dental materials journal. 2018;37(2):317-324. https://doi.org/10.4012/dmj.2016-220
Yu M, You D, Zhuang J, Lin S, Dong L, Weng S, Zhang B, Cheng K, Weng W, Wang H. Controlled release of naringin in metal-organic framework-loaded mineralized collagen coating to simultaneously enhance osseointegration and antibacterial activity. ACS applied materials & interfaces. 2017;14;9(23):19698-705. https://doi.org/10.1021/acsami.7b05296
Sharma A.R., Lee Y.H., Bat-Ulzii A., Chatterjee S., Bhattacharya M., Chakraborty C., Lee S.S. Bioactivity, Molecular Mechanism, and Targeted Delivery of Flavonoids for Bone Loss. Nutrients. 2023;15(4):919. https://doi.org/10.3390/nu15040919
Wong S.K., Chin K.Y., Ima-Nirwana S. The osteoprotective effects of kaempferol: the evidence from in vivo and in vitro studies. Drug design, development and therapy. 2019;13:3497-3514. https://doi.org/10.2147/DDDT.S227738
Liu H., Yi X., Tu S., Cheng C., Luo J. Kaempferol Promotes BMSC Osteogenic Differentiation and Improves Osteoporosis by Downregulating miR-10a-3p and Upregulating CXCL12. Mol. Cel Endocrinol 2021;520:111074. https://doi.org/10.1016/j.mce.2020.111074
Tsuchiya S., Sugimoto K., Kamio H., Okabe K., Kuroda K., Okido M., Hibi H. Kaempferol-immobilized titanium dioxide promotes formation of new bone: effects of loading methods on bone marrow stromal cell differentiation in vivo and in vitro. International Journal of Nanomedicine. 2018;1665-1676. https://doi.org/10.2147/IJN.S150786
Ranjbar F.E., Farzad-Mohajeri S., Samani S., Saremi J., Khademi R., Dehghan M.M., Azami M. Kaempferol-loaded bioactive glass-based scaffold for bone tissue engineering: in vitro and in vivo evaluation. Scientific Reports. 2023;13(1):12375. https://doi.org/10.1038/s41598-023-39505-8
Wang A., Yuan W., Song Y., Zang Y., Yu Y. Osseointegration effect of micro-nano implants loaded with kaempferol in osteoporotic rats. Frontiers in Bioengineering and Biotechnology. 2022;10:842014. https://doi.org/10.3389/fbioe.2022.842014
Moorthy T., CH M.N., Anburaj G., Ahmed S. S., Gopinath V., Munuswamy-Ramanujam G., Kamath M. S. Controlled release of kaempferol from porous scaffolds augments in-vitro osteogenesis in human osteoblasts. Journal of Drug Delivery Science and Technology. 2023;83:104396. https://doi.org/10.1016/j.jddst.2023.104396
Malviya V., Tawar M., Burange P., Jodh R. A Brief Review on Resveratrol. Asian Journal of Research in Pharmaceutical Sciences. 2022;12(02):157-162. https://doi.org/10.52711/2231-5659.2022.00027
Zhang L.X., Li C.X., Kakar M.U., Khan M.S., Wu P.F., Amir R.M., Li J.H. Resveratrol (RV): A pharmacological review and call for further research. Biomedicine & pharmacotherapy. 2021;143:112164. https://doi.org/10.1016/j.biopha.2021.112164
Li L., Yu M., Li Y., Li Q., Yang H., Zheng M., Han Y., Lu D., Lu S., Gui L. Synergistic anti-inflammatory and osteogenic n-HA/ resveratrol/ chitosan composite microspheres for osteoporotic bone regeneration. Bioactive Materials. 2021;6(5):1255-1266.
https://doi.org/10.1016/j.bioactmat.2020.10.018
Biswas L., Niveria K., Verma A. K. Paradoxical role of reactive oxygen species in bone remodelling: implications in osteoporosis and possible nanotherapeutic interventions. Exploration of Medicine. 2022;3(4):393-413. https://doi.org/10.37349/emed.2022.00102
Karimi‐Soflou R., Mohseni‐Vadeghani E., Karkhaneh A. Controlled release of resveratrol from a composite nanofibrous scaffold: Effect of resveratrol on antioxidant activity and osteogenic differentiation. Journal of Biomedical Materials Research Part A. 2022;110(1): 21-30. https://doi.org/10.1002/jbm.a.37262
Sri K. H., Ganapathy D., Nallasamy D., Venugopalan S., Sivaswamy V., Kamath S. M. Sustained release of resveratrol from fused deposition modelling guided 3D porous scaffold for bone tissue engineering. Process Biochemistry. 2023;131:188-198. https://doi.org/10.1016/j.procbio.2023.06.001
de Nadai Dias F. J., de Andrade Pinto S. A., Rodrigues dos Santos Jr A., Mainardi M. D. C. A. J., Rischka K., de Carvalho Zavaglia C. A. Resveratrol-loaded polycaprolactone scaffolds obtained by rotary jet spinning. International Journal of Polymer Analysis and Characterization. 2022;27(5):289-301. https://doi.org/10.4015/S1016237223500278
Alavi M., Yarani R., Sreedharan M., Thomas S. Micro and nanoformulations of catechins for therapeutic applications: recent advances and challenges. Micro Nano Bio Aspects. 2023;2(1):8-19. https://doi.org/10.22034/MNBA.2023.382922.1021
Sistanipour E., Meshkini A., Oveisi H. Catechin-conjugated mesoporous hydroxyapatite nanoparticle: A novel nano-antioxidant with enhanced osteogenic property. Colloids and Surfaces B: Biointerfaces. 2018;169:329-339. https://doi.org/10.1016/j.colsurfb.2018.05.046
Pietryga K., Panaite A. A., Pamuła E. Composite scaffolds enriched with calcium carbonate microparticles loaded with epigallocatechin gallate for bone tissue regeneration. Engineering of Biomaterials. 2022;166:12-21. https://doi.org/10.34821/eng.biomat.166.2022.12-21
Byun H., Jang G. N., Lee J., Hong M. H., Shin H., Shin H. Stem cell spheroid engineering with osteoinductive and ROS scavenging nanofibers for bone regeneration. Biofabrication. 2021;13(3):034101. https://doi.org/10.1088/1758-5090/abd56c
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