Nanomedicine applications in orthopedic medicine: state of the art

Figures & data

Figure 1 Scheme shows potential applications of nanomedicine in orthopedic medicine.

Abbreviations: BG, bioactive glass; TCP, tricalcium phosphate.

Table 1 Typical materials used in orthopedics, including nanostructures

Materials	Features	Structure
Polymers		2D/3D scaffolds; nanofibers; nanocoating
Natural polymers
Collagen^Citation13,Citation14	Low immune response; good substrate for cell adhesion; chemotactic; low mechanical properties
Chitosan^Citation15,Citation16	Hemostatic; promotes osteoconduction and wound healing
Hyaluronic acid^Citation17^–^Citation19	Chemotactic when combined with appropriate agents; low mechanical properties; minimal immunogenicity
Silk^Citation20^–^Citation22	Promotes cell migration, vascularization, and osteoconduction; high compressive strength
Synthetic polymers
Polylactic-co-glycolic acid (PLGA)^Citation23^–^Citation25	Biocompatible; tunable degradation rates; good mechanical properties; process ability; approved for clinical use in humans
Poly(e-caprolactone)^Citation26^–^Citation28	Low chemical versatility; degradable by hydrolysis or bulk erosion; slow degrading; bioresorbable
Polymethylmethacrylate (PMMA)^Citation29^–^Citation31	Brittle; biocompatible; thermoplastic; low ductility; used as bone cement
Poly(lactic acid) (PLA)^Citation32	Biodegradable; bioabsorbable; thermoplastic; suitable mechanical properties
Polyetheretherketone (PEEK)^Citation33,Citation34	Good mechanical properties; chemically and physically stable; biologically inert and safe; poor osteointegration
Metals
Titanium alloys^Citation35^–^Citation37	High corrosion resistance; osteoconductive	Nanotubes; nanorods; nanoparticles; UFG
Cobalt–chromium alloys^Citation38,Citation39	Excellent friction resistance; high corrosion resistance	Nanostructures
Silver^Citation40^–^Citation42	Antimicrobial/antiviral properties; used as anti-infection coatings	Nanoparticles; nanocoating
Stainless steel^Citation43,Citation44	Low cost; excellent fabrication properties; resistant to a wide range of corrosive agents	Nanostructures
Tantalum^Citation45	Anticorrosive; biocompatible; cost effective; ductile	Nanoparticles
Ceramics
Calcium phosphates^Citation8	Improved cell differentiation; osteoconductive	Nanoparticles; nanocoating
Hydroxyapatite^Citation46,Citation47	Slow biodegradation rate; low fracture toughness; good osteointegration	Nanoparticles; nanorods; nanocoatings
Bioactive glass^Citation27,Citation48	Brittle and weak; enhanced vascularization	Nanoparticles; nanocoatings
Metallic oxides (eg, alumina, zirconia, titania)^Citation49	Favorable wear and corrosion properties; good biocompatibility	Nanoparticles; nanotubes; nanocoatings
Carbon materials
CNTs/CNFs^Citation50,Citation51	Excellent electrical conductivity and mechanical strength; low density	Nanofibers; nanotubes
Graphene/graphite^Citation52	High tensile strength; thermal and electrical conductivity; reflexivity	Nanosheets
Diamond^Citation53	Superior mechanical and tribiological properties	Nanoparticles; nanocrystals; nanorods
Composites		Nanoparticles/nanorods/nanotubes/nanosheets/nanofibers reinforced composites
Ceramic nanophase in a ceramic or polymer matrix^Citation54^–^Citation56
Carbonaceous nanophase in a ceramic or polymer matrix^Citation50,Citation57	Better osteoconductivity; tailorable degradation rate; enhanced mechanical and biological properties; supporting cell activity
Metallic nanophase in a ceramic or polymer matrix^Citation58^–^Citation60
Polymer–polymer composites^Citation61,Citation62

Abbreviations: 2D, two-dimensional; 3D, three-dimensional; UFG, ultrafine-grained; CNT, carbon nanotube; CNF, carbon nanofiber.

Figure 2 Effects of surface nanostructuring on the cell viability, differentiation, and bactericidal capacity of CP Ti.

Notes: (A, B) SEM images of TiO₂ nanotube layer and microporous titanium, respectively. (C, D) The nanostructuring effect on the MG-63 cell proliferation and ALP activity. Reproduced with permission of Dove Medical Press, from Xia L, Feng B, Wang P, et al. In vitro and in vivo studies of surface-structured implants for bone formation. Int J Nanomedicine. 2012;7:4873; permission conveyed through Copyright Clearance Center, Inc.³⁵ Antibacterial activity of TiO₂ nanotubes. Figure 2C *P<0.05, n=9; Figure 2D. *P<0.05, n=7. (E) under UV radiation and (F) in the presence of silver NPs of different sizes. Copyright © 2014. John Wiley & Sons, Inc. Reproduced from Esfandiari N, Simchi A, Bagheri R. Size tuning of Ag-decorated TiO₂ nanotube arrays for improved bactericidal capacity of orthopedic implants. J Biomed Mater Res A. 2014;102(8):2625–2635.⁴¹

Abbreviations: CP, commercially pure; SEM, scanning electron microscope; ALP, alkaline phosphatase; UV, ultraviolet; NPs, nanoparticles; h, hours; TDN, titanium dioxide nanotubes.

Table 2 Surface modification methods for titanium and its alloys implants

Surface modification method	Modified layer	Objectives
Hydrothermal treatment^Citation100	TiO2 film with different surface morphologies	Improving the biological performance of implants through enhanced bioactivity and osteoconductivity
Sol-gel^Citation114	Nanometer-scale films such as titania, zirconia, and calcium phosphate	Surface nanostructuring to improve biocompatibility and bioactivity
Chemical etching^Citation107	Nanometer-sized and micrometer-sized surfaces	Better attachment of osteoblastic cells along with improved protein adsorption and osseointegration
Physical methods
Machine grinding^Citation97	Micrometer-rough and nanometer-rough	Creating surface topography for greater osseous contact with improved mechanical interlocking
Abrasive blasting^Citation96	Ti surfaces
Sandblasting^Citation97
Electrochemical processing^Citation41,Citation97	Nanoscale surfaces such as TiO2 nanotubes	Improving the viability, attachment, and proliferation of cells; increasing binding sites
Nanostructured coatings
Nanoceramics^Citation53	Thin film coatings such as Al2O3, HA, calcium phosphate, CS/GO, and ND	Improving in vivo and in vitro biocompatibility, bioactivity, and bactericidal capacity
Nanopolymers^Citation115
Nanocomposites^Citation113

Abbreviations: HA, hydroxyapatite; CS, chitosan; GO, graphene oxide; ND, nanodiamond.

Figure 3 Effect of carbon nanostructures on the performance of electrodeposited polysaccharide coatings on Ti foils.

Notes: (A) SEM image of CS/GO (30 wt%) coating.¹¹³ (B) MTT viability and (C) SEM morphology of MG-63 cells cultured on the surface of the CS/GO coating. (D) A SEM image of alginate/BG/ND film. Copyright © 2013. Elsevier B.V. Reproduced from Mansoorianfar M, Shokrgozag MA, Mehrjoo M, Tamjid E, Simchi A. Nanodiamonds for surface engineering of orthopedic implants: enhanced biocompatibility in human osteosarcoma cell culture. Diam Relat Mater. 2013;40(0):107–114.⁵³ (E) Formation of apatite phases on the surface of the alginate coating after 28 days of incubation in the SBF and (F) its MG-63 cell viability response. (G) The antibacterial performance of the CS/GO coating containing vancomycin against Staphylococcus aureus. Insets: plate counting images showing S. aureus bacteria colonies after 120 min incubation for the CS-30GO film containing (a) 0, (b) 0.5 and (c) 1 g/l antibiotics. (H) Cumulative drug release of the CS/GO (30 wt%) coating. Copyright © 2015. Elsevier B.V. Reproduced from Ordikhani F, Ramezani Farani M, et al. Physicochemical and biological properties of electrodeposited graphene oxide/chitosan films with drug-eluting capacity. Carbon. 2015;84(0):91–102.¹¹³ *Denotes significant difference between TPS and EPD coatings (P<0.05). ^#Denotes significant difference between CS and composite coatings (P<0.05).

Abbreviations: SEM, scanning electron microscope; CS, chitosan; GO, graphene oxide; BG, bioactive glass; ND, nanodiamond; SBF, simulated body fluid; TPS, tissue culture polystyrene; EPD, electrophoretic deposition; MTT, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide.

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