Effect of Zn and Co doping on antibacterial efficacy and cytocompatibility of spark plasma sintered hydroxyapatite

Abstract

Hydroxyapatite [Hap, Ca10(PO4)6(OH)2] is one of the most preferred bioceramic material for orthopedic implants and coatings due to its stoichiometric similarities with human hard tissues. However, foreign body implantation inside human body sometimes leads to bacterial film formation over the implant surface causing the implant failure, thereby needing a revision surgery. This study attempts to select the better dopant between zinc (Zn) and cobalt (Co) as per the antibacterial efficacy when doped in Hap. To prepare antibacterial transition‐metal‐doped Hap, Zn and Co are doped in Hap as per the chemical formula Ca10−x Mx(PO4)6(OH)2, (M = Zn or Co and x = 0.24) to improve antibacterial efficacy. Phase and microstructural characterization by Rietveld refinement, scanning electron microscopy (SEM), and Fourier transformation infrared spectroscopy (FT‐IR) confirms the doping. Evaluation of antibacterial activity against E coli reveals that both Zn‐ and Co‐doped Hap shows antibacterial property with the latter being more effective (zone of inhibition ~3 mm more) for the same level of doping. Inductively coupled plasma‐mass spectrometry confirms the presence of ~676 ppb Co+2 and ~303 ppb Zn+2 after leaching. In addition, cytotoxicity assay with NIH3T3 cell line reveals cytocompatibility of both the compositions with either dopant. The effect of spark plasma sintering on densification and mechanical properties of Co‐doped Hap is investigated for the first time and compared with Hap with the same level of Zn doping. It appears that Co‐doped Hap attains higher densification (~7% more) and fracture toughness (~2 times better) as compared to that of Zn‐doped counterpart (densification: 86% and fracture toughness: 0.75 ± 0.12 MPa √m). Thus, this study suggests that Co‐ and Zn‐doped Hap are promising candidates for bone tissue engineering with improved antibacterial properties and in addition, Co‐doped Hap can attain higher density and offer better fracture toughness than that of Hap doped with Zn.

Multifunctional Hydroxyapatite Composites for Orthopedic Applications: A Review

“…coli compared to Zn (ZOI, 13.11 ± 0.11 mm). Apart from their respective inherent ability, the higher leachability of Co 2+ (∼676 ppb) when compared to that of Zn 2+ (∼303 ppb) is also considered a legitimate reason for the difference in antibacterial efficiency . From another study conducted by Bhattacharjee and co-workers, Co-doped HAp was achieved as per the chemical formulas Ca 10 (PO 4 ) 6 Co x (OH) 2−α and Ca 10– x Co x (PO 4 ) 6 (OH) 2 ( x = 0, 0.2 (HAp2Ca and HAp2OH), and 0.3 (HAp3Ca and HAp3OH)) by means of a wet chemical processing method.…”

“…Being a bioactive material, the metal dopants enable the formation of bone apatite layers on the HAp surface, eventually leading to stable interfacial bonding. Moreover, these materials can also accelerate the formation and proliferation of osteoblasts. ,, The addition of metal dopants (Zn, Li, Mg, Si, Sr, and Mn) augments osteogenesis, osteoblast proliferation, and neovascularization and thereby enhances bone healing. Bone healing using an artificial scaffold is a postnatal activity that represents many of the ontological events that occur during the embryonic development of the skeletal system, and this is depicted in Figure a and b.…”

“…In addition, bioactive materials are capable not only to form an organic bond with surrounding tissue to progress into a normal tissue but also to release antibacterial/antioxidant agents . The primary examples of bioactive materials include hydroxyapatite (HAp), bioactive glass (BG), and biopolymers. , With time, multifunctional porous active biomaterials were developed with an aim to combine the effect of several active additives (Ag, − Ce, , Co, , etc.) with the same biomaterial to achieve synergetic effects .…”

“…6 The primary examples of bioactive materials include hydroxyapatite (HAp), bioactive glass (BG), and biopolymers. 5,7 With time, multifunctional porous active biomaterials were developed with an aim to combine the effect of several active additives (Ag, 8−11 Ce, 6,12 Co, 13,14 etc.) with the same biomaterial to achieve synergetic effects.…”

“…59 To eradicate the bacterial infection, novel antibacterial HAp composites are developed by the incorporation of various nanomaterials having antibacterial property, like Ag, Co, Zn, etc. 6,13 Antioxidants like CeO 2 , when incorporated along with antibacterial agents, were observed to exhibit a synergistic effect in the developed orthopedic products as they scavenge the reactive oxygen species (ROS) and act as reinforcements as well, leading to the betterment of implant quality. 6 Scaffold porosity also plays a vital role in tissue infiltration and strong mechanical interlocking between bone and scaffold as they provide sufficient stability at the bone−biomaterial interface.…”