Nanotechnology for treating osteoporotic vertebral fractures

Abstract

Osteoporosis is a serious public health problem affecting hundreds of millions of aged people worldwide, with severe consequences including vertebral fractures that are associated with significant morbidity and mortality. To augment or treat osteoporotic vertebral fractures, a number of surgical approaches including minimally invasive vertebroplasty and kyphoplasty have been developed. However, these approaches face problems and difficulties with efficacy and long-term stability. Recent advances and progress in nanotechnology are opening up new opportunities to improve the surgical procedures for treating osteoporotic vertebral fractures. This article reviews the improvements enabled by new nanomaterials and focuses on new injectable biomaterials like bone cements and surgical instruments for treating vertebral fractures. This article also provides an introduction to osteoporotic vertebral fractures and current clinical treatments, along with the rationale and efficacy of utilizing nanomaterials to modify and improve biomaterials or instruments. In addition, perspectives on future trends with injectable bone cements and surgical instruments enhanced by nanotechnology are provided.

Keywords: bone cement; kyphoplasty; nanomaterials; osteoporosis; pedicle screw; radiopacifier; vertebral fracture.

Figure 1

Schematic of vertebroplasty and kyphoplasty procedures, which are both minimally invasive, percutaneous surgical approaches that can internally stabilize a fractured vertebral body via injection of self-hardening biomaterials like bone cement. Note: The difference between vertebroplasty and kyphoplasty procedures is the utilization of a balloon that is inflated to create a cavity in the compressed vertebral body prior to injection of the cement. The blue lines represent the catheter; the yellow ovals represent the balloon; and the white oval represents the cement in each instance.

Figure 2

Fluorescent images showing osteoblast adhesion (nuclei stained with DAPI) on PMMA modified with nano and conventional MgO and BaSO₄ (magnification 100×). (A) Pure PMMA; (B) conventional MgO; (C) nano MgO; (D) conventional BaSO₄; and (E) nano BaSO₄. Notes: Osteoblast adhesion was significantly increased on nanoparticle-modified PMMA compared with pure PMMA or PMMA modified with conventional particles. Copyright ©2008. Dove Medical Press. Reproduced from Ricker A, Liu-Snyder P, Webster TJ. The influence of nano MgO and BaSO₄ particle size additives on properties of PMMA bone cement. Int J Nanomedicine. 2008;3:125–132. Abbreviations: PMMA, polymethylacrylate; DAPI, 4,6-diamidino-2-phenylindole.

Figure 3

An alginate-based hybrid system consisting of electrospun nanofibrous mesh for growth factor delivery and bone repair. Notes: (A) Scanning electron micrograph of electrospun nanofibrous mesh illustrating the smooth and bead-free nanofibers. Tubular bone implants made from nanofibrous mesh (B) without and (C) with perforations. (D) Scheme of mesh tube implant in segmental bone defect, where modular fixation plates are used to stabilize the bone and a nanofibrous mesh tube is placed in a defect 8 mm long. Also, alginate hydrogel with or without rhBMP-2 may be injected into the hollow tube. (E) Photograph of the surgical site after placing a perforated mesh tube. (F) The mesh tube was retrieved 1 week after implantation and the mesh tube was cut open, where the alginate was still present inside the defect. (G) Curve showing release kinetics of rhBMP-2 from alginate over 21 days in vitro, and sustained release of the rhBMP-2 was observed during the 1st week. Reproduced from Biomaterials. Vol 32. Kolambkar YM, Dupont KM, Boerckel JD. An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. 65–74. 2011, with permission from Elsevier. Abbreviation: rhBMP, recombinant human bone morphogenetic protein-2.

Figure 4

Morphology, mechanical properties and biocompatibility of bone cements containing functionalized nanoparticles. Notes: Scanning electron micrographs of (A) ZNFT bone cement containing functionalized ZrO₂ nanoparticles and (B) BNFT bone cement containing functionalized BaSO₄ nanoparticles. Representative compressive stress-strain curves for (C) various bone cements containing ZrO₂ particles, and (D) bone cements containing BaSO₄ particles. (E) Twenty-four-hour osteoblast adhesion tests showing cell adhesion density as a function of bone cements type. ^ΨCompared to bone cements containing micron BaSO₄ particles, adhesion was found to be greater on bone cements containing BaSO₄ nano-particles functionalized with TMS (P<0.05). ^€WRT bone cements containing micron ZrO₂ particles, adhesion was found to be greater on bone cements containing unfunctionalized ZrO₂ nano-particles (P<0.05) and ZrO₂ nano-particles functionalized with TMS (P<0.1). Copyright ©2010. Dove Medical Press. Reproduced from Gillani R, Ercan B, Qiao A, Webster TJ. Nanofunctionalized zirconia and barium sulfate particles as bone cement additives. Int J Nanomedicine. 2010;5:1–11. Abbreviations: BM, BaSO₄ micron particles; BN, BaSO₄ nanoparticles; TMS, 3-(trimethoxysilyl) propyl methacrylate; BNFT, BaSO₄ nanoparticles functionalized with TMS; ZM, ZrO₂ micron particles; ZN, ZrO₂ nanoparticles; ZNFT, ZrO₂ nanoparticles functionalized with TMS.

Figure 5

Morphology and mechanical property of electrospun nanofibrous P(DLLA-CL) balloons (ENPBs). Notes: (A) Photograph of inflated (top) and non-inflated (bottom) ENPBs. Arrows indicate the diameter of balloon catheter. (B) Scanning electron micrograph of electrospun nanofibers in an ENPB. (C) Typical force-displacement curves for natural bones, nature bones injected with CPC, natural bones injected with PMMA, and natural bones with balloon insertion and CPC injection, respectively. Reprinted from Nanomedicine. Vol 9. Sun G, Wei D, Liu X, et al. Novel biodegradable electrospun nanofibrous P(DLLA-CL) balloons for the treatment of vertebral compression fractures. 829–838;2013, with permission from Elsevier. Abbreviations: CPC, calcium phosphate cement; ENPB, electrospun nanofibrous poly(d,l-lactide-co-ε-caprolactone) balloon; NB, nature bone; PMMA, polymethylacrylate.

Figure 6

Images and failure loads of metallic interference screws before and after coating with HA. Notes: Photographs of metallic (Ti6Al4V) interference screws (A) before and (B) after coating with nano-HA, (C) bioabsorbable interference screws, and (D) metallic screws retrieved after implantation. (E) Failure loads of metallic interference screws coated with micro-HA and nano-HA after extraction, compared with uncoated screws. Reproduced from Springer and Eur J Orthop Surg Traumatol. Vol 24, 2014:813–819. Influence of micro- and nano-hydroxyapatite coatings on the osteointegration of metallic (Ti6Al4V) and bioabsorbable interference screws: an in vivo study. Aksakal B, Kom M, Tosun HB, Demirel M. With kind permission from Springer Science and Business Media. Abbreviation: HA, hydroxyapatite.

Figure 7

Morphology and antibacterial capacity of conventional Ti, nanorough Ti, nanotubular Ti, and nanotextured Ti. Notes: (A) Scanning electron micrographs of (clockwise) conventional Ti as purchased, nanorough Ti fabricated by electron beam evaporation, nanotextured Ti fabricated by anodization for 1 minute in 0.5% hydrofluoric acid at 20 V, and nanotubular Ti fabricated by anodization for 10 minutes in 1.5% hydrofluoric acid at 20 V. Scale bar 200 nm. (B) Increased fibronectin adsorption on nanorough, nanotubular, and nanotextured Ti surfaces compared with conventional Ti surface. (C) Decreased Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa colonies on nanorough and conventional Ti surfaces compared with nanotubular and nanotextured Ti surfaces after 1 hour. (D) The highest percentage of live bacteria colonies for S. aureus, S. epidermidis, and P. aeruginosa attached to the nanorough Ti surfaces after 1 hour compared with the conventional, nanotextured, and nanotubular Ti surfaces. *P<0.1 compared to nanotextured Ti; **P<0.01 compared to nanotextured Ti; ***P<0.05 compared to nanotubular Ti; ^#P<0.05 compared to conventional Ti; ^##P<0.01 compared to nanotubular Ti; ^###P<0.1 compared to nanotubular Ti; ⁺P<0.1 compared to conventional Ti; ⁺⁺P<0.1 compared to nanotubular Ti for respective bacteria lines. Reprinted from Biomaterials. Vol 31. Puckett S, Taylor E, Raimondo T, Webster TJ. The relationship between the nanostructure of titanium surfaces and bacterial attachment. 706–713;2010, with permission from Elsevier. Abbreviation: Ti, titanium.

Figure 8

Transmission electron micrographs of PEEK-HA nanocomposites with (A) 5.0 vol% and (B) 15.0 vol% HA content. (C) Ultimate tensile strength and microhardness of PEEK-HA nanocomposites as a function of HA content. Note: The arrow in C means the micro-hardness of the nanocomposites. Reprinted from Mater Sci Eng A. Vol 528 (10–11). Wang L, Weng LQ, Song SH, Zhang ZG, Tian SL, Ma R. Characterization of polyetheretherketone–hydroxyapatite nanocomposite materials. 3689–3696; 2011, with permission from Elsevier. Abbreviations: HA, hydroxyapatite; PEEK, polyether-ether-ketone.