Titanium Fiber Plates with Suitable Elastic Modulus and Porous Structure Facilitate Bone Tissue Repair

Titanium (Ti) is one of the most commonly used biomedical materials in orthopedics and dentistry. The excellent biocompatibility of Ti with high bone affinity makes it a suitable material for biomedical applications. Nevertheless, the higher Young’s modulus of Ti (≈110 GPa) than that of the cortical bone (10-30 GPa) causes stress shielding, leading to bone embrittlement. Since stress shielding is unavoidable with the use of Ti plates, it is generally recommended to remove them from the bone after completion of bone repair. However, removal of the Ti plate involves many risks; bone formation around the plate poses difficulty in removal of the plate besides pain and infections due to surgery. Researchers at Department of Orthopaedic Surgery, Shinshu University School of Medicine, Mechanical Systems Engineering, Shinshu University, Faculty of Engineering, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University and Department of Applied Physical Therapy, Shinshu University School of Health Sciences, Japan have suggested the use of Ti fiber plates in place of the conventional Ti plates. Since the Young’s modulus of Ti fiber plates are similar to that of the cortical bone, stress shielding effect can be minimized. In addition, the porous structure of Ti fiber plates could act as scaffolds and promotes cell attachment.

The Ti fiber plates were prepared using Ti fibers (ASTM Grade 1 with 99.52% purity) with a mean diameter of 20 μm and a mean length of 500 μm (Fig. 1(a)). The Ti fibers were molded into a plate by simultaneously applying a compression stress of 1000 MPa and a shearing load of 400 kN at room temperature (Fig. 1(b)) followed by sintering at 300 K. The resultant Ti fiber plates had a thickness of 0.2 mm, Young’s modulus of ≈30 GPa and uniform porous structure with 30–40% porosity and 60–80 μm pore diameter (Fig. 1(c). The utility of the plates for repair of bone fracture and bone tissue regeneration was evaluated under in vitro and in vivo conditions.

Fig. 1 (a) SEM image of Ti fibers; (b) schematic diagram of the process used for preparing Ti fiber plates; and (c) SEM image of the Ti fiber plate

In vitro test results indicate that the extent of osteoblast adhesion and cell proliferation on the Ti fiber plates are quite similar to that of the conventional Ti plates. However, the difference in expression levels of cell-adhesion-related genes between cells on the Ti fiber plates and the cells on conventional Ti plates, suggests the existence of a difference in the mode of cell adhesion at the gene level between these two plates. The unique 3D structure of the Ti fiber plate is considered responsible for the increased level of osteoblast adhesion than those observed for the conventional titanium plates with a simple planar structure. In vivo study in rabbits with comminuted fracture at the center of the ulnar stem indicates that placing the titanium fiber plate in close contact with the fractured bone helps to immobilize and repair of small bone fragments.

Fig. 2 (a) Fixing of titanium fiber plate to the ulna using miniature screws for the repair of comminuted fracture (arrow mark) in rabbits; (b) Scout radiograms and (c) μCT images taken at Week 4 post-operation indicate complete bone union in the titanium fiber plate group but not with the control group

Unlike the conventional Ti plate, the Ti fiber plates could be easily prepared by compressing Ti fibers at room temperature without changing the fiber shape, which makes the process cost-effective and commercially viable. By suitably altering the length and thickness of the Ti fibers as well as the extent of compression and shear stress, Ti fiber plates with varying thickness, surface properties, porosity, Young’s modulus and strength can be prepared. Due to its malleability, the Ti fiber plates can be manually reshaped into a curved 3D structure and customized to the required size and shape of the fixation site for bone regeneration. The porous structure of Ti fibers with 30–40% porosity and 60–80 μm pore diameter is considered to be suitable for bone regeneration. Since the Young’s modulus of Ti fiber plate is similar to that of cortical bone, the deleterious stress shielding effect can be minimized and hence, it can remain implanted even after the fracture is healed. The use of pure Ti fibers ensures a better biosafety.

The Ti fiber plate is easy to deform manually and hence it can be shaped optimally during surgery to prevent loss of bone fragments from comminuted fractures. Since the titanium fiber plate is thin and easily deformable, it is suitable for fractures at sites where the space around the plate is limited such as ulnar and phalangeal fractures. The titanium fiber plates also allow holes to be drilled for insertion of small screws at given sites during surgery. Hence, the Ti fiber plates can be used for a wide variety of fracture treatments including bone regeneration. Titanium fiber plates are not so tough to withstand high mechanical loads. In addition, rubbing of Ti fibers against one another could produce wear particles. These limitations still remain to be solved.

T.S.N. Sankara Narayanan

For more information, the reader may kind refer: Takashi Takizaw et al., Titanium Fiber Plates for Bone Tissue Repair, Adv. Mater. 2017, 1703608, DOI: 10.1002/adma.201703608

Development of a hierarchical micro/nano-porous structure on acupuncture needles for the treatment of colorectal cancer

Acupuncture is considered to be an effective therapy for treating functional disorders, pain relief, drug abuse and psychiatric disorders. The treatment mechanism involves the release of endogenous opiates and neurotransmitters, which are mediated through electrical stimulation of the central nervous system. In order to increase the intensity of the stimuli, it is necessary to use thicker needles and/or deeper insertion of the needles. However, a similar effect could be achieved by increasing the surface area of the needles. Researchers at the Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu Haany University, Republic of Korea and Flux Photon Corporation, USA, have fabricated a porous structure with hierarchical micro/nano-scale conical pores on the surface of conventional stainless steel acupuncture needles.

Conventional stainless steel acupuncture needles (CN) (length: 8 cm; diameter: 0.18 mm) were anodized in ethylene glycol medium modified with the addition of 0.2 wt. % NH₄F + 2.0 vol. % deionized water at 20 V for 30 min to form a porous structure with hierarchical micro/nano-scale conical pores (PN). The morphological features of CN and PN are shown in Fig. 1. The CN possess a smooth surface (Fig. 1(a)) whereas a hierarchical micro/nano-scale porous surface topology is developed after anodization (Figs. 1(b), 1(c) and 1(d)). The surface area of PN (1.03 m²∙g⁻¹) is ~ 25 times higher than CN (0.04 m²∙g⁻¹).

Fig. 1 Morphological features of (a) conventional acupuncture needle (CN);  and (b, c, d) nanoporous acupuncture needle (PN); (c, d) high resolution images.

The surface modified stainless steel acupuncture needles (PN) enhanced the therapeutic effects of colorectal cancer (CRC) treatment in rats.

T.S.N. Sankara Narayanan

For further information, the reader may kindly refer: Bo Ram Lee et al., Enhanced Therapeutic Treatment of Colorectal Cancer Using Surface-Modified Nanoporous Acupuncture Needles, Scientific Reports, 7: 12900,  DOI:10.1038/s41598-017-11213-0

 

Growth-accommodating implants – laying the foundation for a new paradigm of paediatric device development

Medical implants are often available in fixed size. The inability of such devices to accommodate with normal tissue growth remains a challenge, particularly in case of children. Hence, development of implant devices that could correct themselves in accordance with anatomical deformities and easily accommodate with tissue growth is highly warranted.

Researchers at the Harvard Medical School, USA and University College Dublin, Ireland have developed a growth-accommodating device that consists of a tubular braided sleeve and a biodegradable polymer core (Eric N. Feins et al., A growth-accommodating implant for paediatric applications, Nature Biomedical Engineering, 1 (2017) 818–825).

Fig. 1 (a) Schematic of a degradable polymer core (dark blue) placed inside a braided sleeve to control sleeve diameter, coupling inner polymer degradation to braided sleeve (and overall device) elongation; (b) A dissolvable spherical sucrose core (red) inside a nitinol biaxial braid acts as a degradable polymer surrogate. Upon immersion in water, the sucrose core gradually dissolves leading to a gradual decrease in the braided sleeve diameter along with a concomitant autonomous elongation; (c) Variation in length and diameter of the braided sleeve during core degradation.

A hydrophobic surface-eroding, biodegradable and biocompatible polymer poly(glycerol sebacate) (PGS) was used as the base material. The rationale behind the choice of PGS was justified based on its minimal swelling in water, ability to offer the requisite mechanical properties to resist compressive forces from the braided sleeve and capability to maintain structural integrity throughout degradation. To minimize the stretching of PGS to less than 5%, it was treated at 155 °C for 86 h in vacuum, which maximizes its cross-linking leading to the formation of extra-stiff PGS (ESPGS). The ESPGS was used as the polymer core while the braided sleeve was made of nitinol alloy.

The concept behind the development involves coupling the degradation of a surface-eroding polymer core to the braid length and overall device elongation. After implantation, once the polymer core starts to degrade, the braided sleeve begins to thin out and elongates in response to surrounding tissue growth (Figs. 1(a) and 1(b)), without the necessity for any additional interventions. Since the sleeve length and diameter of the braid are inversely related,  thinning of the sleeve results in its elongation (Fig. 1(c)).

The flexible nature of the braided sleeve and polymer contributes to the durability of the device and no evidence of fatigue failure of either the braided sleeve or the ESPGS core could be observed during in vivo studies using animal models.

By altering the number and thickness of braid fibres, the braid geometry and rate of degradation of the polymer core, it would be possible to modify the device elongation profile to match a wide spectrum of clinical applications.

Variability in the polymer erosion rate is the current limitation of the proposed device and achieving uniform degradation of polymer core will be the focus of future work.

T.S.N. Sankara Narayanan

For more information, the reader may kindly refer Eric N. Feins et al., A growth-accommodating implant for paediatric applications, Nature Biomedical Engineering, 1 (2017) 818–825.

Meta-biomaterials: Combining rational design and additive manufacturing towards the development of next generation medical devices

Meta-biomaterials are part of the emerging concept of metamaterials that possess a desired combination of mechanical  (i.e. negative Poisson’s ratio), mass transport (e.g. permeability and diffusivity) and biological properties (e.g. tissue regeneration performance).

Total hip replacement (THR) implants often encounter mechanical failure at the implant-bone interface (aseptic loosening), which limits their lifetime. The femoral part of THR is repeatedly loaded under bending for ~2 million cycles per year, which creates tensile loading and compression on either side of the neutral axis of the implant. The implant–bone interface is more susceptible to failure when subjected to tension as compared to compression. Since bone exhibits higher mechanical strength in compression than in tension, the side of the THR that experiences tension (i.e. retracts from the bone) is more susceptible to interface failure. Hence, it is necessary to design THR implants in such as way to create compression on both sides of its neutral axis.

Researchers at Delft University of Technology, The Netherlands, 3D Systems, Leuven, Belgium and University Medical Centre Utrecht, The Netherlands have demonstrated a proof-of-concept of applying a combination of rational design and additive manufacturing in the design of meta-biomaterials to improve longevity of implants. (Reference: Helena M. A. Kolken et al., Rationally designed meta-implants: a combination of auxetic and conventional meta-biomaterials, Mater. Horiz., 2017, DOI: 10.1039/C7MH00699C)

Two types of meta-biomaterials, one with a negative Poisson’s ratio (i.e. auxetic) (‘A’ in Fig. 1) while the other one with a positive Poisson’s ratio (i.e. conventional) (‘B’ in Fig. 1) were designed. Subsequently, both types of meta-biomaterials were combined to create a hybrid meta-biomaterial with different values of the Poisson’s ratio (‘C’ in Fig. 1). The meta-implants were then designed using these combined meta-biomaterials, in which the Poisson’s ratio of the meta-biomaterials changed around the neutral axis to compress the implant against the bone on both sides. Totally, six different combinations were designed and they were manufactured by selective laser melting (SLM) using biomedical-grade titanium alloy Ti6Al4V-ELI powders.

Fig. 1 Schematic drawings showing the topological designs of (A) auxetic and (B) conventional meta-biomaterials, (C) hybrid meta-biomaterials (left); and design of meta-implants (right): (C1) control type 1 with conventional hexagonal honeycombs. (H1) Hybrid type 1 with a 50/50 cell ratio. (C2) Control type 2 with re-entrant hexagonal honeycombs, showing the different parts of the implant: (1) top, (2) porous region and (3) bottom. (H2) Hybrid type 2 with a 50/50 cell ratio and a solid core. (H1) Hybrid type 1 showing the different parts of the implant: (1) top-middle-bottom and (2) porous region. (H3) Hybrid type 3 with a 70/30 cell ratio

Fig. 2 shows the photographs of the selective laser melted Ti6Al4V-ELI THR meta-implants (Fig. 2(a)); the test set-up in which the THR implant was loaded including bone-mimicking materials (Fig. 2(b)); and the horizontal strains in the bone-mimicking materials surrounding the meta-implants at t = 0 and t = 180 s at 1.5 mm displacement for C1, C2, H1, H2 and H3 (Fig. 2(c)).

Fig. 2 (a) Additively manufactured (selective laser melting) Ti6Al4V-ELI THR meta-implants; (b) test set-up in which the THR implant was loaded including bone-mimicking materials; and (c) Horizontal strains in the bone-mimicking materials surrounding the meta-implants at t = 0 and t = 180 s at 1.5 mm displacement for C1, C2, H1, H2 and H3.

The findings of the study clearly reveal that meta-implant with design H2 compress against the bone under repetitive loads that are applied during gait and other daily activities. According to the Hoffman’s failure criterion, this combination of compression and shear is less deleterious than tension and shear.

The current proof-of-concept study demonstrated the feasibility of applying rational design and metamaterials for the development of the next generation of medical devices. Nevertheless, the performance of these materials has to be evaluated using animal models and clinical trials.

T.S.N. Sankara Narayanan

For further information, the reader may kindly refer: Helena M. A. Kolken et al., Mater. Horiz., 2017, DOI: 10.1039/C7MH00699C)

 

Smart Dental Braces – Pushing the boundary of personalized health care electronics to the next level

Batteries contribute to the overall weight and size of implantable devices such as cardiac peacemakers and neuro-stimulators. The rigid encapsulation and requirement for proper insulation from corrosive materials limit the widespread utility of batteries for implantable devices. Besides weight and design aspects, the batteries have to be biocompatible and offer a high performance. Hence, development of light weight, physically flexible, biocompatible, high performance batteries are highly warranted to meet the demands of advanced personalized health care applications.

Researchers at King Abdullah University of Science and Technology (KAUST), Saudi Arabia, lead by Prof. Muhammad M. Hussain, have demonstrated a transfer-less method to develop a flexible, light-weight, biocompatible, high performance lithium ion batteries (LIBs) for implantable devices. They have also proposed a strategy for integrating the LIBs with flexible electronics and embedding them in a three-dimensional (3D) printed dental brace for orthodontics application (npj Flexible Electronics 1, Article No:7 (2017) doi:10.1038/s41528-017-0008-7)

Polydimethylsiloxane (PDMS) was used as the carrier substrate. A bulk LIB (thickness: 130 μm) was flipped on to the PDMS substrate. The Si (at the base of the LIB) was etched using xenon difluoride (XeF₂) at a rate of 67 nm/s for 36 min (50 cycles). The surface roughness was monitored using atomic force microscopy (AFM) to optimize the conditions of XeF₂ etching. The thinned LIB was removed from the PDMS (Fig. 1(a)). Complete removal of the Si substrate from the thinned LIB results in a free standing and physically flexible active stack (thickness: 30 μm). It consists of SiO₂ (insulation layer), Al (cathode current collector), lithium cobalt oxide (cathode), lithium phosphorous oxynitride (electrolyte), Ti (anode current collector) and protective layers at the top surface (Fig. 1(b)). In spite of a large reduction in thickness (from 130 μm to 30 μm), the flexible LIB experienced only a lower strain (five times less) when compared to the bulk, for a 10 mm bending. Cell cultures grown on LIB for 3 to 5 days exhibited a healthy proliferation of the cells, which confirmed the biocompatibility of LIB. The flexible LIB possess a light weight (236 μg for each microcell of 2.25 × 1.7 mm) and exhibits a very high energy density (200 mWh/cm³) with a capacity retention of up to 70% after 120 cycles.

Fig. 1 (a) Schematic of the fabrication of flexible LIBs; and (b) cross sectional morphology of the flexible thinned battery and its components

Polyethylene terephthalate (PET) was used as the base for the flexible electronic device. It was metallized with Al (thickness: 0.023 mm). Interconnections were patterned using 1.06 μm ytterbium-doped fiber laser. Flip-chip technology and stencil printing allowed placement of the components. A conductive silver epoxy was used to bond the LIBs and LEDs. The LIB in the flexible electronic device exhibits minimal strain since most of the stress is experienced by the PET film. Transparent orthodontic brace was prepared by 3D printing using a clear resin. Finally, the flexible electronic device is integrated with the 3D printed orthodontic brace. The schematic of the integration of the flexible thinned LIBs with the flexible electronics and 3D printed dental braces is shown in Fig. 2(a). A pictorial representation of how the device fits in conformably onto the human dental arch is shown in Fig. 2(b).

Fig. 2 (a) Schematic of the integration of the flexible thinned LIBs with flexible electronics and 3D printed dental braces; and (b) Pictorial representation of how the device fits in conformable manner onto the human dental arch.

T.S.N. Sankara Narayanan

 

 

For more information, the reader may kindly refer: Arwa T. Kutbee et al., npj Flexible Electronics 1, Article No:7 (2017) doi:10.1038/s41528-017-0008-7