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International Journal of Bioprinting                           Osteogenic, antibacterial CpTi-MgOCu implants




            National Ambulatory Medical Care survey, 70% of patients   4.2. Antibacterial performance due to Cu addition
            visiting clinics for orthopedic surgery-related issues in   Copper was used as a sterilizing agent for chest wounds,
            2015–2016 were over 45 years of age . Age has a significant   as recorded in Egyptian medical texts dating back
                                        [57]
            impact on the quality of recovery, as the quality of bone and   5000  years  ago [64] .  After  it  has  been  used  for  medical
            its healing ability significantly decrease with age . Elderly   purposes in the generations that follow, the antibacterial
                                                  [58]
            patients,  who  often  suffer  from  immunocompromised   potential of copper was discovered in the 19th
            bone health, usually have a prolonged recovery after   century [65] . In 2011, copper was the first antimicrobial
            surgery, which compromises their overall health. The   metallic material approved by the U.S. Environmental
            infections at the implant site requiring revision surgery   Protection Agency (EPA) [65] . Amid the COVID-19
            have a huge impact on the health of patients, particularly   pandemic, in 2021, U.S. EPA approved the use of
            the individuals with age-related decline of bone health,   copper-based disinfectants owing to the performance
            leading to a further reduction in life expectancy. There is   of copper and copper alloys against SARS-CoV-2, i.e.,
            an unmet need in metallic implants for materials that can   the virus responsible for COVID-19 [66] . Realizing the
            provide faster bone remodeling performance and infection   potential of Cu as an antibacterial agent, extensive
            prevention  capabilities  beyond  what  titanium  currently   research has been conducted on incorporating Cu
            offers. Current strategies include cemented implants with   into Ti. Cu is a necessary trace element in the human
            Ti6Al4V as the bulk material for strength with a surface   body in a wide variety of tissues, but higher amounts
            coating of bioactive calcium phosphate or hydroxyapatite.   of Cu can cause cytotoxicity leading to liver cirrhosis
            Despite the superior  in  vivo performance toward early-  and  neurologic  abnormalities [67] .  A  debate  persists  on
            stage  osseointegration,  one of  the  major  shortcomings   the optimum amount of Cu in Ti [68-71] . In this study,
            of  cemented  implants  is  delamination  of  the  calcium   with 3 wt.% addition of Cu in CpTi, the H&E-stained
            phosphate coating due to poor metal-ceramic bonding.   bone sections show no signs of cytotoxicity. However,
            Instead, porous titanium metallic coating is a popular   the mineralized bone formation in CpTi-MgO-Cu was
            choice as it can abate the risk of coating failures . In order   observed to be lower than that in CpTi-MgO. Although
                                                 [7]
            to induce osteogenic properties in these porous titanium   3 wt.% Cu did not cause cytotoxicity, there was a delayed
            coatings, MgO addition in CpTi can potentially solve the   early-stage osseointegration performance. CpTi-MgO-
            coating failure issue.                             Cu still showed 3.5× mineralized bone formation at
                                                               the interface than CpTi, showing superior osteogenic
            4.1. Osteogenesis due to MgO addition              performance.
            Mg plays an essential role in promoting bone calcification
            and remodeling. Mg deficiency in the bone has         Early-stage osseointegration greatly affects the patient’s
            been  linked  with  degenerative  bone  diseases  such  as   recovery time. With CpTi-MgO-Cu used as a metallic
            osteoporosis [59,60] . Mg regulates intracellular calcium ion   coating on bulk Ti6Al4V alloy at load-bearing sites,
            concentration,  pH,  transporters,  enzymes,  and  protein   coating failures in cemented implants can be avoided. At
            synthesis [25,61] . Biodegradable Mg implants for low-  the same time, enhanced early-stage osseointegration can
            load bearing bone–graft applications have been studied   be achieved owing to the osteogenic properties of MgO,
            extensively [62,63] . Moreover, incorporating MgO in calcium   and inhibition of bacterial infections at the surgery site can
            phosphate has  enhanced  cellular  proliferation  in vitro   prevent revision surgeries.
            and osteogenic performance  in  vivo [8,59] .  In this  study,
            incorporating MgO in CpTi enhanced osteogenesis at the   5. Conclusion
            bone–implant interface. With just 1 wt.% MgO addition   Early-stage osseointegration at the implant surface is
            in CpTi, mineralized bone formation at the BIC increased   critical in the post-surgery healing of elderly patients
            four-fold compared to that in CpTi (Figure 3c). Bone   with degraded bone health. Bio-inertness and non-
            remodeling  at the  implant surface follows  osteoblast   antibacterial nature of Ti result in aseptic loosening, which
            recruitment followed by osteoid lining and eventual   necessitates surgical intervention. Without adequate
            maturation  of  bone.  CpTi  histology  images  show  an   material intervention to enhance tissue integration and
            osteoid lining at the bone–implant interface. For CpTi-  prevent  polymicrobial  infections,  revision  procedures
            MgO, histology images show mineralized bone directly   would further degrade the patient’s health and constitute
            apposed to the implant’s outer surface, indicating an   a potential risk of morbidity. Ti6Al4V bulk implants
            enhanced bone remodeling process compared to CpTi.   coated with bioactive ceramics, such as osteogenic MgO
            With superior osseointegration performance, we believe   and antibacterial Cu, tend to cause coating failures due
            CpTi-MgO can potentially replace ceramic coatings in   to their weak metal-ceramic bonding. In this study, we
            cemented implants and prevent coating failures.    propose the addition of 1 wt.% MgO and 3 wt.% Cu to


            Volume 9 Issue 6 (2023)                        561                          https://doi.org/10.36922/ijb.1167
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