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    • br Conclusion br Conflicts of interest br

    2022-11-25


    Conclusion
    Conflicts of interest
    Acknowledgements The authors are grateful to the Ministry of Food Processing Industries, Govt of India (V45/MFPI/R&D/2000 Vol.IV) and Department of Biotechnology, New Delhi, Govt. of India (BT/475/NE/TBP/20132), American Bamboo Society and Ned Jaquith Foundation, USA for providing financial assistance to conduct this research work.
    Introduction Bone injury and chain reactions mediated free radical species (reactive oxygen species, ROS) generation, is a critical factor to ponder upon. ROS affects the long-term stability of bone/implants, mediate apoptosis of Dasatinib Monohydrate and osteocytes, leading to osteoclastogenesis thereby favoring bone resorption [1]. ROS triggers responses like: (i) arresting cell proliferation, (ii) decreasing cell growth and/or differentiation, and (iii) promoting cell death by activating various signaling pathways [2,3]. ROS production in diseased states and aging overwhelms the antioxidant mechanisms (creating oxidative stress) of the body [4]; post-implantation, in such patients (disease, fracture and age-being the contributors), the oxidative stress secludes the material from the surrounding tissue and also leads to cytotoxicity [5]. Rodent bone resorption was facilitated by free radicals generated in vitro and in vivo [6]. Furthermore, an in vivo study on rabbits reported that significant levels of oxidative stress are induced in the tissues surrounding a bone implant (especially, ceramic and titanium in comparison to polyethylene) [7]. Therefore, incorporating an antioxidant like ascorbic acid, vitamins, etc. may aid in accelerated healing of fractured bones/implants (scavenging ROS) and in-turn also provide a protection against osteoporosis [4,7,8]. Hydroxyapatite (HA, Ca10(PO4)6(OH)2), in the character of orthopedic implants, exhibits promising bioactivity on the ground that it shows structural and chemical similarity to human bone skeleton (Ca/P ratio 1.67) [9,10]. Notwithstanding the excellent biological property of hydroxyapatite, it possess poor mechanical strength [11] and in-order to enhance the same, a second material is used in combination/as a reinforcement, for instance carbon nanotube (CNT), silver, alumina, zirconia, etc. [[12], [13], [14]]. The role of rare-earth elements in bone tissue engineering has been reported in some studies, for example, the use of lanthanum oxide as a reinforcement material for HA, which showed enhancement of the microstructural and mechanical properties [15,16]. The rare earth ions are gaining popularity due to their similarity with calcium ions (calcium ion mediated signaling regulates various cellular processes like proliferation, differentiation and apoptosis) [17]. Due to the structure of cerium oxide (CeO2-x) nanoparticles (NPs), the autoregenerative redox mechanism between Ce3+ and Ce4+ oxidation states is utilized as a biological trigger for designing a drug delivery system (mesoporous silica based) [18]. The role of cerium oxide nanocrystals to reduce ROS in human mesenchymal stem cells and human dermal fibroblasts exposed to H2O2 has been demonstrated [19,20]. Ceria NPs have now been reported to offer enzyme mimetic properties, like superoxide oxidase, oxidase and catalase; hence can be used in biomedicine [21], drug delivery [22], bioanalysis [23,24] and bio-scaffolds [25,26]. Ceria NPs are able to show ocular [27], neuronal [28], and radioprotection [29], in addition to a defense to heart from inflammatory and oxidative injury [30]. Literature reports the use of glass (lanthanide- doped; Ce/La; 2.5 wt%) in combination with HA (97.5 wt%), wherein a passable biocompatibility (improvement in cell adhesion and proliferation) was seen, indicating its potential application in bone tissue engineering [31]. Primary mouse embryonic fibroblast proliferation was stimulated by citrate-stabilized ceria NPs by decreasing intracellular ROS [32]. 3D glass foam scaffolds containing tailor made ceria NPs (synthesized in water as medium) could improve the osteoblastic differentiation of human mesenchymal stem cells by enhancing collagen formation [19,33]. A nanocomposite system composed of galantamine, ceria and HA species was found to be an effective anti-Alzheimer agent by removing hazardous ROS and helping in nerve cell repair [34]. In combination with poly (d,l-lactic-co-glycolic acid), ceria NPs leads to increase in elastic modulus and ultimate tensile strength, and also cardiac stem cells and mesenchymal stem cells viability with enhanced proliferation [35]. Though the precise physiological effect of cerium is still unknown, but it is understood that ceria NPs facilitates metabolism and protects tissues (as antioxidant). It has been observed that addition of 1, 5, 10 wt% of ceria to bovine-HA matrix, sintered at 1200 to 1300 °C gave rise to enhanced micro-hardness from 564 to 583 HV, respectively, with highest compression strength ~107 MPa (for 5, 10 wt% ceria addition) [16].