An appropriate selection of the materials in the biomedical applications is critical for the long-term success of implants. Accepted biomaterials must meet the following requirements: (i) Biocompatibility. The biocompatibility is always the foremost consideration for implant material selection. The chosen materials must be non-toxic to the human body, so inflammatory or allergic reactions would not be triggered after implantation. (ii) Corrosion and wear resistance. The longevity of implants is particularly determined by the material corrosion and wear. It was reported that the corrosion and wear of implanted materials might lead to sensitivity reactions within human body [
4] and also had potential risks in generating local tumours [
5]. In addition, malfunctions of the corroded and worn implants would be caused after a long-term service [
6]. Considering that the corrosion and wear of implant materials could be accelerated in practical uses due to the more complicated chemical and physical conditions in human body, biomaterials have typically high demands on the resistance to corrosion and wear. (iii) Mechanical properties. Skeletal bone implants, such as artificial hip and knee joints, aim to bear patient’s body weight [
7]. Thus, suitable mechanical properties of biomaterials are needed to minimize the fatigue failure after millions of cyclic loading. (iv) Economic manufacturing. From the industrial point of view, the manufacturing processes are required to be economically viable.
To match the requirements above, biomaterials such as metallic alloys, ceramics and polymers have been used or being investigated. A detailed review of the typical biomaterials is given in the following sections.
2.1 Stainless steel
Stainless steel contains a minimum of 10.5% (mass fraction) chromium and varying amounts of other elements [
8], which was first discovered in the early 1990s [
9] and quickly became notable for its ease in manufacturing and low cost. In the past century, it has been widely used in many applications such as the construction of exhaust manifolds, surgical instruments, food handling, vehicle decoration, etc. Stainless steel is renowned for holding the longest record for being used as a biomaterial. Of the many grades in stainless steel family, the austenitic 316L stainless steel is the only category that is used for bioimplant applications. This kind of stainless steel is favoured for the inexpensiveness and not exhibiting ferromagnetism. The austenitic structure also offers this grade an excellent toughness, even down to cryogenic temperatures. According to the cytotoxicity evaluation standards, 316L stainless steels exhibit relatively good biocompatibility [
10‐
14]. The first utilization of stainless steel in biological orthopaedics was reported in the 1930s, when Wiles [
15,
16] achieved the total hip replacement. In the following decades, this kind of material evoked tremendous scientific interests in the fabrication of bioimplants and presently being used in large quantities by a factor of 10%–20% in the market [
17].
As the mechanical properties of stainless steel can be controlled in a wide range, it allows the fabricated products possessing optimal ductility and strength for medical uses. Such characteristic is especially attractive in the bioimplants manufacturing. In general, stainless steel possesses much greater elastic modules (about 200 GPa) than human bones (10–30 GPa) [
14]. The relatively high ultimate tensile strength and fracture toughness guarantee a satisfactory mechanical performance, as the material can bear significant loads and undergo sufficient plastic deformation before failure [
13,
18]. Nevertheless, the mechanical working conditions inside a living body greatly differ from the external environment. Specifically, skeletal bones suffer cyclic loading in the course of patients walking. The estimated step number of a patient over 20 years is over 1 × 10
7 cycles [
7], such cyclic loading may fracture the material below its ultimate tensile strength or yield strength [
18]. In fact, stainless steel implants typically subject to fatigue damage as its fatigue strength is relatively low [
19‐
21]. Therefore, the stainless steel is now mainly being used in short-term implant devices.
Another reason for the short service period of stainless steel is that the material is not sufficiently resistant to corrosion. It was reported that the initiation of fatigue cracks in stainless steel was closely correlated to the corrosion pits [
22,
23]. In a long-term application, corrosion would not only degrade the implant mechanical function but also be likely to release ions such as iron, chromium, nickel and molybdenum to human body [
24‐
26]. Although there is no report on the adverse effects induced by iron ions released from stainless steel implants, the excess of other tracer elements may increase the risk of eliciting allergy reactions or toxic effects [
25]. Thereinto, Ni is a typical high-risk element from the perspective of metal toxicity problems [
17]. It is worth noting that the extent of corrosion in 316L stainless steel based bioimplants is unrelated to either alloy composition or the implantation duration [
4].
Wear of the stainless steel based bioimplants is recognized as another major clinical issue. It may lead to implant loosening, along with adverse cellular responses and inflammation [
18]. A recent achievement in grain refinement of metallic materials allowed the enhancement of the material properties and an improved sliding wear resistance was presented [
27].
In general, due to its low fabrication cost and satisfactory biocompatibility, stainless steel still plays an important role in implant applications at the stage. However, the low fatigue strength, as well as poor corrosion and wear resistance, confines stainless steel to temporary devices. To maintain its prevail role in implant applications, special fabrication methods for producing nickel-free, high-nitrogen and ultra fine-grained stainless steels are required.
2.2 Cobalt-based alloy
The first adaption of cobalt-based alloy in biomedical implantation was reported in 1936 for hip arthroplasty [
28]. In the following ten years, its medical applications in orthopaedics were significantly expanded and notable successes were achieved [
8,
18]. Based on the composition, biomedical Co-based alloys are typically categorized into two groups. One is Co-Cr-Mo alloy, which contains 27%–30% Cr and 5%–7% Mo. Recently, with the longevity expectancy increased to more than 20 years, this material tends to be extensively employed as structural materials in permanent bioimplants. For instance, the Co-Cr-Mo alloy with an ultra-high molecular weight polyethylene as a lining is currently the commonest match of prosthetic knees and ankles [
18,
29]. Co-Ni-Cr-Mo is another type of cobalt alloy, whose composition includes Ni (33%–37%), Cr (19%–21%) and Mo (9%–11%). It came into use in the biomedical field later than Co-Cr-Mo and was mainly wrought before employed in making heavy load-bearing joints, such as the stems of prostheses [
8,
29,
30].
Cobalt alloys have excellent biocompatibility in bulk form, which is closely related to its satisfactory resistance to corrosion [
18,
31]. Numerous researchers have revealed that cobalt alloys are highly corrosion resistant even in chloride-rich environments. It is believed that the passive oxide layers formed spontaneously on the alloy surface are responsible for such characteristics. The layers serve as barriers in corrosive environments and thus hinder the corrosion process [
30,
32‐
34]. X-ray photoelectron spectroscopy (XPS) analysis shows that the formation of oxide layers is largely attributable to the high Cr content. Mo and Ni also played a similar but insignificant role. Although the major alloying compositions such as Co, Cr, Mo and Ni are all essential trace elements in the human body, they would be biologically toxic when excessive, and result in damaging kidney, liver, lungs and blood cells [
35‐
39]. Thus, the release of particles or ions caused by material fatigue and aseptic loosening is a big concern for Co-alloy biomaterials [
18].
In comparison to stainless steel, cobalt-based alloys have a longer lifespan and less likely to experience fatigue fracture [
30]. This is due to the crystallographic nature of the major element, cobalt, ensures the alloy possesses superior mechanical properties [
18]. The elastic modulus and ultimate tensile strength of the material are 230 GPa and 430–1028 MPa, respectively, which is almost 10 times higher than that of human cortical bones [
30,
35]. Such outstanding mechanical properties make cobalt alloys suitable for a wide variety of orthopaedic applications. However, an obvious disadvantage brought by the high elastic modulus is the “stress shielding effect”. Specifically, the replaced implant may bear basically all the load around the site and prevent the needed stress being transferred to the bones nearby. This effect would gradually weaken the stimulus for bone remodelling and therefore lead to bone atrophy [
18,
40]. Moreover, the high costs involved in manufacturing have put Co-based alloys at another disadvantage when it comes to medical market. Although imperfect, cobalt alloys are still regarded as a favourite metallic implant material in joint bearing applications [
18].
2.3 Titanium-based alloy
Titanium and its alloys are favourable biomaterials due to the combination of several remarkable characteristics, such as low density, high strength, excellent biocompatibility and ideal mechanical properties [
1,
29,
41]. The demand of Ti-alloys in medical applications has surged since the 1970s, and the upward trend of employing them as bioimplant materials is likely to continue. Of all the titanium-based products, Ti-6Al-4V is the most commonly used material which takes up about 45% of the total production [
18]. Interestingly, the preliminary purpose of developing Ti-6Al-4V alloy was for aerospace applications, while its attractive biocompatibility led it into the field of biomaterials [
3,
42].
The element titanium is non-existent in the human body and its biological role is unclear [
43], but what is certain is that titanium is non-toxic. It has been well reported that titanium is totally inert to body environment [
29,
44]. If titanium was excessive in a living body, excretion would take place without any absorption or digestion [
45]. The inertness seems to make Ti and Ti-alloy a perfect material for implants. However, ill effects such as osteomalacia, allergic reaction and peripheral neuropathy were still found in Ti-alloy implanted bodies, which were likely due to the release of aluminium and vanadium from the alloy [
1,
3,
46]. The development of new generation of Ti-alloys (
β-titanium alloys) is now in progress. Attempts of replacing Al and V by relatively safer elements such as Mo, Ta, Nb and Zr have been carried out [
47,
48]. However, it should be noted that long-term follow-up investigation data are absent [
18]. As mentioned, the biocompatibility of an implanting material is highly depended on its corrosion resistance. There is no doubt that Ti and Ti-based alloys are facile princeps in this regard. Similar to cobalt-based alloys, by virtue of a passive oxide film, the corrosion resistance of Ti-alloys is more than an order of magnitude greater than that of stainless steels [
1,
18,
29]. The major difference is that due to the intrinsic properties of matrix element titanium, the corrosion resistance of Ti-alloy does not need to be enhanced through alloying [
18].
The mechanical properties of Ti-based alloys are influenced by the variation of the interstitial and impurity levels [
18]. In another case, the second generation of Ti-based alloy Ti-Nb-Zr-Ta, also known as TNZT system, realized the lowest elastic modules of any metallic alloy biomaterials with the help of new alternative alloying elements [
47,
49]. It is worth noting that although the elastic modulus of Ti alloys is lower than Co-based alloys, the stress shielding effect remains an issue as the effect can only be reduced but impossible to be prevented [
1]. In terms of the ultimate tensile stress, the values tested from
β-titanium alloys are comparable with that from stainless steels but lower than Co-based alloys [
8,
18]. Ti-alloys have been proved to possess greater wear resistance than Co-alloys according to hip joint simulation tests [
42]. However, externally applied stresses may damage the unstable oxide layer, and hence generate hard oxide particles in the human body. The debris would in turn further break down the oxide layer and cause more severe surface damages to the implants. Therefore, Ti-based alloys are more recommended to be applied as components of modular constraints, rather than articulate against other materials [
18].
A comparison of metallic biomaterials of stainless steel, cobalt-based alloys, titanium and Ti-based alloys was summarized by Long and Rack [
42]. The characteristics and utilizations of these metallic materials can be seen in Table
1. The information provided a clear perspective of why Ti and Ti-alloys are regarded as the most promising metallic biomaterial to date.
Table 1
Characteristics of orthopaedic metallic implant materials [
42]
Designation
|
ASTM F-138 (“316 LDVM”) | ASTM F-75 | ASTM F-75 (ISO 5932/II) |
| ASTM F-799 | ASTM F-136 (ISO 5832/II) |
| ASTM F-1537 (cast and wrought) | ASTM F-1295 (cast and wrought) |
Principal alloying elements\% (mass fraction)
|
Fe(bal.) | Co(bal.) | Ti(bal.) |
Cr(17–20) | Cr(19–30) | Al(6) |
Ni(12–14) | Mo(0–10) | V(4) |
Mo(2–4) | Ni(0–37) | Nb(7) |
Advantages
|
Cost, availability | Wear resistance | Biocompatibility |
Processing | Corrosion resistance | Corrosion |
| Fatigue strength | Minimum modulus |
| | Fatigue strength |
Disadvantages
|
Long term behaviour | High modulus | Power wear resistance |
High modulus | Biocompatibility | Low shear strength |
Primary utilizations
| | |
Temporary devices (fracture plates, screws, hip nails) | Dentistry castings | Used in THRs with modular (CoCrMo or ceramic) femoral heads |
Used for THRs stems in UK (high nitrogen) | Prostheses stems | Long-term, permanent devices (nails, pacemakers) |
| Load-bearing components in TJR (wrought alloys) | |
2.4 Polymer
Due to the ease of manufacturability, adequate mechanical properties and low cost, polymers are now frequently applied in biomedical uses. One typical application of polymer in bio-implantology is being used as acetabular cups. In incongruent joints such as knee and ankle, stress concentration is easy to occur at the interface between two incongruent surfaces and hence damage the neighbouring bones. The existence of cartilage layers and synovial fluid in human body plays a predominant role in decreasing such heterogeneous stresses. However, for artificial joints made by brittle metallic materials, the impact of residual stresses could be significant and is hard to be removed. Therefore, researchers turned their attention to polymer materials. In the 1960s, Charnley [
50] first realized low-friction arthroplasty with the help of a small-diameter metallic femoral head articulating with a polymeric acetabular cup. Such design immediately drew enormous attention for artificial joints manufacturing. After all these years, this concept is still retained in total joint replacement arthroplasty [
42]. Although the mechanical feature of low elastic modulus helps polymer biomaterials to avoid stress-shielding effect after implanting, the relatively low strength hinders their potential application in hard tissues.
Polymers are also favoured for their flexibility as they can be fabricated into various forms to meet demands of different applications, such as solids, fibres, films and fabrics. But for the same reason, the weakness of the material makes its wear behaviour unsatisfactory [
51]. Therefore, surface modifications of polymer biomaterials are usually evolved to enhance the functionality before putting into use [
52].
2.5 Ceramics
The exploitation of ceramics as biomaterials started in the 1970s [
53]. The unique properties such as excellent biocompatibility have made ceramic a favourable material for bone repair and joints substitutions [
53‐
55]. Based on the reaction level in a living body, bioceramics are usually categorized into three types, namely, bioinert ceramics, bioactive ceramics and bioresorbable ceramics [
53,
56]. The bioinert ceramics are basically inert in a human body. This may be due to a thin non-adherent fibrous layer would usually be formed at the interface of ceramic and bone [
55]. Such kind of material is valued in joint replacement prostheses because of the excellent durability. The bioactive ceramics refer to the materials that possess osteoconductivity or direct bone-bonding ability, one typical example of this bioceramic is bioglass
® [
55,
57,
58]. As they would spontaneously induce a biological bonding to the living tissues nearby after implanting, this type of ceramic was widely applied in the coating of metal prostheses [
52]. The third category, bioresorbable ceramic, degrades in the host body over time and would be gradually replaced by the regenerated bones [
55]. They provide a better control of the biomaterial resorption and bone substitution processes [
59]. Tricalcium phosphate and calcite are typical bioresorbable ceramics [
59,
60].
Two most well-known representatives of bioinert ceramics are alumina and zirconia [
55,
61]. They are both favoured for the biocompatibility as the chemical compositions are either common ions in the physiological environment or haveminor toxic effect to human bodies [
62]. Alumina’s increasing popularity lies in the combination of modest fracture toughness, satisfactory wear properties, excellent corrosion resistance and high compression resistance. The high elastic modulus and hardness that are only second to diamond make alumina a tremendous potential for loading bearing systems in artificial joints [
53]. After Boutin [
63] reported the first employment of a total hip prosthesis with an alumina head and alumina socket in 1971, the expansion of alumina ceramic in clinical uses was enormous in the later decades. Now, alumina bioceramic is most commonly seen in femoral heads in conjunction with a polymer acetabular cup and a metallic femoral stem for hip replacements, as well as wear plates in knee replacements [
54,
64]. However, it was necessary to further improve its reliability as slow crack growth was found in alumina ceramic with time in service [
65]. Other defects such as low fracture strength, high brittleness, hard to fabricate, etc., also impair its potential uses.
Zirconia is thought to be a good alternative to alumina because it has similar merits as alumina, but possesses substantially higher fracture toughness [
61,
66]. The use of zirconia in the biomedical applications was first introduced by Helmer and Driskell [
67]. In 1988, Christel et al. [
68] illustrated the feasibility of zirconia in manufacturing ball heads for total hip replacement, which subsequently became its main application. Compared to the utilization of alumina in hip prostheses, zirconia bioceramic allows a significant reduction in the diameter of the femoral head, which enables a higher degree of freedom for the mobility of the joint [
62]. At present, Tetragonal zirconia polycrystal (TZP) was selected by the ball head manufacturers and only a few cases of clinical failure were reported [
61,
69,
70]. Due to the satisfactory fatigue resistance, over 300 000 TZP femoral heads have been implanted till 2002 [
62]. There is no doubt that this material is experiencing a significant era in its development as bioceramic. Efforts have recently been made to apply zirconia ceramics in the total knee replacement. Nevertheless, such bioceramic is still regarded as a new material in the biomedical field, whether that the failure rate may increase with time passes is yet to know [
70,
71]. Attention should also be paid to the growth of slow subcritical cracks and the deterioration of toughness with time [
62]. Hence, long-term evaluations and further studies are required to optimize its performances in clinical application.
Calcium phosphate ceramic such as hydroxyapatite (HA) is regarded as a good bioceramic for bone substitutes due to its outstanding biocompatibility, low density, chemical stability and structural similarity to bone minerals [
72,
73]. Apart from these material characteristics, the most remarkable feature of HA in the biomedical application is its bone bioactiveness, i.e., it promotes hard tissue ingrowth and osseointegration after being implanted into the human body. Since the concept of biological fixation was proposed in the late 1960s, which suggested that prosthetic components could be firmly bonded to the host bone by ongrowth or ingrowth without using bone cement, HA coatings have been used more and more widely on the metallic biomaterials [
74,
75]. In the past half-century, numerous studies have confirmed the enhancement effect on bone tissue ingrowth stimulated by the HA coatings through analyzing the bonding interface between HA and surrounding bone tissues [
76,
77]. From the biomedical perspective, such features realize achieving the distinct therapeutic benefit of faster rehabilitation for patients. As the current trend in bioceramic research is improving the material biological properties through exploring the unique advantages of nanotechnology. Research attempts have been made on improving the HA’s crystallinity degree and reducing the grain size to nanometric [
78]. Compared to conventional HA, synthetic hydroxyapatite with nanoscaled features present a higher surface area and looser crystal-to-crystal bonds, which allows a more homogeneous resorption by osteoclasts [
72].
Although the clinical results from HA coating are promising, the poor mechanical properties of HA remain a major concern. Because the bulk HA lacks sufficient tensile strength and the bending strength is lower than 100 MPa, mechanical failure is likely to occur after long service time [
75]. Furthermore, the significant brittleness of bioceramics hinders their applications in load-bearing implants [
78]. This is the main reason why HA is commonly coated onto a metal core or incorporated into polymers as composites. Even though it has been reported that HA-coated metallic bioimplants indeed possess favourable surface bioactivity, the poor ceramic/metal interfacial bonding cannot be ignored as they may trigger severe structure failure [
78]. Again, the inferior mechanical properties of HA should take the responsibility of poor coating stability [
79]. Great research efforts have been made to enhance the low bonding strength at the HA/metal interface. As the coating methods directly influence the layer adhesion strength and reliability, advances on coating processes are believed to be the key to solve the problem.