materials Review Metallic Biomaterials: Current Challenges and Opportunities Karthika Prasad 1,2,3,*, Olha Bazaka 4, Ming Chua 1, Madison Rochford 1, Liam Fedrick 1, Jordan Spoor 1, Richard Symes 1, Marcus Tieppo 1, Cameron Collins 1, Alex Cao 1, David Markwell 1 ID , Kostya (Ken) Ostrikov 1,2,3 and Kateryna Bazaka 1,2,3,4,* 1 School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD 4000, Australia; [email protected] (M.C.); [email protected] (M.R.); [email protected] (L.F.); [email protected] (J.S.); [email protected] (R.S.); [email protected] (M.T.); [email protected] (C.C.); [email protected] (A.C.); [email protected] (D.M.); [email protected] (K.O.) 2 CSIRO-QUT Joint Sustainable Processes and Devices Laboratory, Commonwealth Scientific and Industrial Research Organization, P.O. Box 218, Lindfield, NSW 2070, Australia 3 Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4000, Australia 4 College of Science and Engineering, Technology and Engineering, James Cook University, Townsville, QLD 4810, Australia; [email protected] * Correspondence: [email protected] (K.P.); [email protected]. (K.B.); Tel.: +61-7-31382165 (K.B.) Received: 27 April 2017; Accepted: 25 July 2017; Published: 31 July 2017 Abstract: Metallic biomaterials are engineered systems designed to provide internal support to biological tissues and they are being used largely in joint replacements, dental implants, orthopaedic fixations and stents. Higher biomaterial usage is associated with an increased incidence of implant-related complications due to poor implant integration, inflammation, mechanical instability, necrosis and infections, and associated prolonged patient care, pain and loss of function. In this review, we will briefly explore major representatives of metallic biomaterials along with the key existing and emerging strategies for surface and bulk modification used to improve biointegration, mechanical strength and flexibility of biometals, and discuss their compatibility with the concept of 3D printing. Keywords: biomaterial; inflammation; implant; advanced materials; surface modification 1. Introduction The use of implants has grown dramatically over the past years, driven by ageing of populations in developed countries, and the desire of the patients to maintain the same level of activity and quality of life. Consequently, the demand for high-performance implantable biomaterials that can address unique challenges in cardiology, vascular therapy, orthopaedics, trauma, spine, dental and wound care has also been increasing steadily. Indeed, the biomaterial market was valued at $94.1 billion USD in 2012 and is currently worth $134.3 billion USD in 2017 [1]. The diversity and functionality of available biomaterials, as well as the methods for their processing and assembly into an implantable device, have also experienced substantial growth, with a wide variety of synthetic, natural and hybrid materials currently on the market [2–5]. Such diversity allows for better selection of the material to meet the specific objectives of the treatment, such as using metals with have high electro conductivity as electrodes in artificial organs, chemically inert materials for permanent replacement of lost function, Materials 2017, 10, 884; doi:10.3390/ma10080884 www.mdpi.com/journal/materials Materials 2017, 10, 884 2 of 33 Materials 2017, 10, 884 2 of 32 or biodegradable materials as a temporary framework for cases where regeneration of lost tissue or function, or biodegradable materials as a temporary framework for cases where regeneration of lost function is possible [6,7]. tissue or function is possible [6,7]. Importantly, recently there has been a significant emphasis on multi-functionality of chosen Importantly, recently there has been a significant emphasis on multi-functionality of chosen biomaterials.biomaterials. For For instance, instance, a temporary scaffold scaffold material material may may not not only only provide provide physical physical support support for fortissue tissue regeneration, regeneration, but but may may also also be be loaded loaded with with biological biological factors, factors, such such as as bone bone morphogenetic morphogenetic protein-2protein-2 (BMP-2), (BMP-2), transforming transforming growth growth factor-factor-bβ (TGF-(TGF-bβ), fibroblast, fibroblast, platelet platelet-derived-derived and and vascular vascular endothelialendothelial growth growth factors factors (FGF, (FGF, PDGF, PDGF, VEGF) VEGF) andand others,others, to stimulate cell cell attachment attachment and and tissue tissue formationformation and/or and/or chemotherapy chemotherapy agents, agents, toto selectivelyselectively target target cancer cancer cells cells not not removed removed during during surgery, surgery, or releaseor release desirable desirable molecules molecules and and ions ions during during scaffoldscaffold biodegradation.biodegradation. This This multi-functionality multi-functionality is is well-illustratedwell-illustrated by by magnesium magnesium implants. implants. MagnesiumMagnesium has has sufficient sufficient tensile tensile strength, strength, resistance resistance to to fracturefracture [8, 9[8,9],], and and light light weight weight to to support support such such load-bearingload-bearing applications applications as as stenting stenting or or small small fracture fracture repairrepair [10 [10],], and and as as it it degrades, degrades, it it releases releases Mg Mg ionsions whichwhich are essential for for human human metabolism metabolism and and are are knownknown to to provide provide stimulatory stimulatory effects effects on on the the generationgeneration of new bone tissue tissue [11]. [11]. The The biodegradation biodegradation kineticskinetics of of the the Mg Mg scaffold scaffold can can be be controlled controlled byby thethe naturenature of the the alloying alloying metals metals (as (as shown shown in inFigure Figure 1),1 ), as wellas well as as certain certain forms forms of of mechanical mechanical processing processing andand coating.coating. FigureFigure 1. (1.a )(a Corrosion) Corrosion rates rates of of Mg-based Mg-based alloys alloys inin physiologicallyphysiologically relevant relevant solutions solutions [12]; [12 ];(b ()b Images) Images of Mg95–xZnxCa5of Mg95–xZnxCa5 (at (at %) %) implanted implanted in in rat rat femurs, femurs, reconstructedreconstructed from inin vivo vivo μµ-CT-CT scans. scans. Note Note visible visible degradation after 30 days for the x = 28 sample, while minimal and no degradation are visible on the degradation after 30 days for the x = 28 sample, while minimal and no degradation are visible on x = 32 and x = 35 samples, respectively [13]; (c) Radiographs of mice distal femora with and without the x = 32 and x = 35 samples, respectively [13]; (c) Radiographs of mice distal femora with and implanted high-entropy CaMgZnSrYb alloy, immediately after implantation, and 4 weeks without implanted high-entropy CaMgZnSrYb alloy, immediately after implantation, and 4 weeks postoperatively. The sample shows no gas formation, no inflammation, and enhanced circumferential postoperatively. The sample shows no gas formation, no inflammation, and enhanced circumferential osteogenesis in the implanted bone (yellow arrow), indicating new bone formation [14]. Reproduced osteogenesis in the implanted bone (yellow arrow), indicating new bone formation [14]. Reproduced with permission from [14,15]. with permission from [14,15]. Imparting multi-functionality on bio-inert metals, such as Ti- and Co- based alloys, is generally achievedImparting by surface multi-functionality modification, onsuch bio-inert as surface metals, structuring such as or Ti- coating and Co- with based bioactive alloys, ceramic is generally and achievedpolymer by thin surface films. modification,Bio-inert materials, such most as surface commonly structuring based on or Ti, coating Co, and with steel, bioactive are critical ceramic for andmany polymer load-bearing thin films. functions, Bio-inert wh materials,ere their mostresistance commonly to corrosion based onprovides Ti, Co, excellent and steel, long-term are critical forstability many load-bearing and reliable mechanical functions, strength, where their with resistance minimal long-term to corrosion toxicity provides to the excellent host locally long-term or on stabilitysystemic and level reliable [16,17]. mechanical These materi strength,als have with excellent minimal tensile long-term strength, toxicity fractureto toughness the host and locally fatigue or on systemicstress [18,19], level [16 and,17 ].over These the materialsyears, they have have excellent found applications tensile strength, in orthopaedics fracture toughness as artificial and joints, fatigue stressplates [18 ,and19], andscrews, over orthodontics the years, they as havebraces found and applicationsdental implants, in orthopaedics cardiovascular as artificialand neurosurgical joints, plates anddevices screws, such orthodontics as components as braces of artificial and dentalhearts, implants,staples, stents cardiovascular and wires. Among and neurosurgical bio-inert materials, devices suchtitanium as components is often the of material artificial of hearts, choice staples,due to a stentsfavourable and wires.combination Among of bio-inertbiocompatibility, materials,