Another major problem leading to implant failures is post

Another major problem leading to implant failures is post-implant infections, majorly due to bacteria adhesion [13,36,37]. A significant decrease in bacterial counts (~65–90%) has been observed in HA and/or CNT-based composites reinforced with 2.5–10 wt% nano Ag [13,38], thus, drawing the conclusion that Ag-reinforced HA matrix can serve as potential antibacterial biocomposites (with 2.5 wt% as the most cytocompatibile, and also moderately anti-bacterial). With respect to the aforementioned criteria, to the best of the information available, the novelty of this NVP-LCQ195 work resides in the fabrication of HA biocomposite, synergistically reinforced with ceria and Ag NPs, to develop composites for orthopedic applications (either as a bio-coating on metal substrates [12,39] for femoral stem [40] or as free standing porous scaffold [41]), intended to, thereby, fulfilling the following objectives: (i) antioxidant activity imparted by ceria NPs (scavenging ROS), (ii) Ag NPs to stamp out the bacterial infections, and (iii) enhancing mechanical and cytocompatible properties with cooperative ceria NPs and Ag NPs reinforcement.
Materials and methods
Results and discussions
Conclusions This study has aimed at the development of hydroxyapatite based composites, ceria and silver reinforced, in contemplation of curbing the oxidative stress caused in the vicinity of implants (causing apoptosis, delayed healing and implant loosening), and resisting the bacterial fatal infections that lead to implant failure. According to the as-obtained data, the incorporation of ceria and Ag NPs in HA matrix was found to be effective in reducing the ROS levels, demonstrating an antibacterial efficacy without compromising the cytocompatibiltiy. The antioxidant activity of ceria reinforced pellets, HA-5C and HA-5C-2.5Ag was obtained to be ~36 and 30%, respectively. The HA-Ag pellet depicted a bacterial resistance of ~61% for E. coli and ~53% for S. aureus, while HA-5C-2.5Ag showed a decrement of ~59% for E. coli and ~50% for S. aureus. The hFOB culture depicted a significant increase on all pellets by day 7, with HA-5C-2.5Ag showing highest values (6.7 times higher than that on HA). The prominent expression of actin filaments, filopodia developing into filopodia-like-extensions, and the formation of matrix like deposition (from morphological analysis) may be attributed to the synergistic effect of ceria (resemblance with calcium ions, hence mediating signaling cascades) and Ag NPs (in low concentration) for enhanced adhesion and metabolic activity supporting cytocompatibility. In addition, the composites showed enhanced mechanical property in comparison to HA (Er ~121–133 GPa). Therefore, the HA-5C-2.5Ag biocomposite may be used as promising candidate for bone substitute (either as a free-standing porous scaffold which can be utilized for internal fixation via surgical means, or as antibacterial bioactive coating on femoral stem (during fabrication of implant) for total hip-replacement) because it provides ROS scavenging (by Ce3+ of ceria NPs) and promotes rapid healing (reduced oxidative stress in the implant vicinity, and enhanced osteoblast adhesion and proliferation), with antibacterial properties (of Ag NPs), enhanced mechanical properties, and improved cell growth and cytocompatibility.
Declaration The authors declare that an Indian patent on “Antioxidant & Antibacterial Property of HA-CeO2-Ag Composite for Bone Tissue Implant” was provisionally filed on November 10, 2016 (Application number: 201611038479) at the Delhi (India) patent office.
Acknowledgments Authors acknowledge funding from MHRD. Nanoindentation facility in Advanced Center for Materials Science, IIT Kanpur, and processing using spark plasma sintering (from FIST grant) at IIT Kanpur is acknowledged. KB acknowledges the initiation of this work for Swarnajayanti Fellowship, Department of Science and Technology, Govt. of India.