In vitro calibration and in vivo validation of phenomenological corrosion models for resorbable magnesium-based orthopaedic implants.

Metallic bioresorbable orthopaedic implants based on magnesium, iron and zinc-based alloys that provide rigid internal fixation without foreign-body complications associated with permanent implants have great potential as next-generation orthopaedic devices. Magnesium (Mg) based alloys exhibit excellent biocompatibility. However, the mechanical performance of such implants for orthopaedic applications is contingent on limiting the rate of corrosion in vivo throughout the bone healing process. Additionally, the surgical procedure for the implantation of internal bone fixation devices may impart plastic deformation to the device, potentially altering the corrosion rate of the device. The primary objective of this study was to develop a computer-based model for predicting the in vivo corrosion behaviour of implants manufactured from a Mg-1Zn-0.25Ca ternary alloy (ZX10). The proposed corrosion model was calibrated with an extensive range of mechanical and in vitro corrosion testing. Finally, the model was validated by comparing the in vivo corrosion performance of the implants during preliminary animal testing with the corrosion performance predicted by the model. The proposed model accurately predicts the in vitro corrosion rate, while overestimating the in vivo corrosion rate of ZX10 implants. Overall, the model provides a "first-line of design" for the development of new bioresorbable Mg-based orthopaedic devices. STATEMENT OF SIGNIFICANCE: Biodegradable metallic orthopaedic implant devices have emerged as a potential alternative to permanent implants, although successful adoption is contingent on achieving an acceptable degradation profile. A reliable computational method for accurately estimating the rate of biodegradation in vivo would greatly accelerate the development of resorbable orthopaedic implants by highlighting the potential risk of premature implant failure at an early stage of the device development. Phenomenological corrosion modelling approach is a promising computational tool for predicting the biodegradation of implants. However, the validity of the models for predicting the in vivo biodegradation of Mg alloys is yet to be determined. Present study investigates the validity of the phenomenological modelling approach for simulating the biodegradation of resorbable metallic orthopaedic implants by using a porcine model that targets craniofacial applications.

Surgically-induced deformation in biodegradable orthopaedic implant devices.

The biocompatibility and mechanical performance of biodegradable metals (e.g. magnesium, iron, and zinc-based alloys) in orthopaedic-targeted applications are contingent on limiting the rate of corrosion in vivo throughout the bone healing. Concurrently, the surgical procedure for the implantation of internal bone fixation devices may impart plastic deformation to the device, potentially altering the corrosion rate of the device. However, the potential effect of the surgical implantation procedure on the mechanochemical performance of metallic degradable orthopaedic devices in vivo remains largely unresolved. The objective of the present study is to develop a robust technique that permits the quantification of the strain introduced due to surgical implantation of degradable orthopaedic devices. Specifically, a novel combined experimental-modelling approach based on 3D laser scanning in situ and the finite element method is utilised to quantify the plastic strain introduced to a bone fixation plate following surgical implantation in a cadaveric porcine model where the plate is based on a ternary magnesium-zinc-calcium alloy (ZX10). The magnitude of plastic strains determined by the above approach for the Mg craniofacial miniplate confirms that the surgical procedure itself has the potential to enhance the corrosion rate of the Mg alloy in an accelerated and potentially localised manner. STATEMENT OF SIGNIFICANCE: Biodegradable metallic orthopaedic implant devices have emerged as a potential alternative to permanent implants, although successful adoption is contingent on achieving an acceptable degradation profile. Plastic strain that is introduced to the device during surgical implantation may influence the resulting degradation behaviour of the implant. In the present work, 3D laser scanning is combined with computer simulation to estimate the level and distribution of surgically-induced plastic strain in a magnesium alloy (ZX10). Subsequently, clinically-relevant pre-strain is shown to influence the rate of corrosion of ZX10 in vitro, indicating the value of such an approach in the design of biodegradable metallic devices under multiaxial loading.

In silico modelling of the corrosion of biodegradable magnesium-based biomaterials: modelling approaches, validation and future perspectives.

Metallic biomedical implants based on magnesium, zinc and iron alloys have emerged as bioresorbable alternatives to permanent orthopaedic implants over the last two decades. The corrosion rate of biodegradable metals plays a critical role in controlling the compatibility and functionality of the device in vivo. The broader adoption of biodegradable metals in orthopaedic applications depends on developing in vitro methods that accurately predict the biodegradation behaviour in vivo. However, the physiological environment is a highly complex corrosion environment to replicate in the laboratory, making the in vitro-to-in vivo translation of results very challenging. Accordingly, the results from in vitro corrosion tests fail to provide a complete schema of the biodegradation behaviour of the metal in vivo. In silico approach based on computer simulations aim to bridge the observed differences between experiments performed in vitro and vivo. A critical review of the state-of-the-art of computational modelling techniques for predicting the corrosion behaviour of magnesium alloy as a biodegradable metal is presented.

Nanostructured cellulose-xyloglucan blends via ionic liquid/water processing.

In this work, the properties of cellulose (CE)/xyloglucan (XG) biopolymer blends are investigated, taking inspiration from the outstanding mechanical properties of plant cell walls. CE and XG were first co-solubilized in an ionic liquid, 1-ethyl-3-methylimidazolium acetate, in order to blend these biopolymers with a varying CE:XG ratio. The biopolymers were then regenerated together using water to produce solid blends in the form of films. Water-soluble XG persisted in the films following regeneration in water, indicating an attractive interaction between the CE and XG. The final CE:XG ratio of the blends was close to the initial value in solutions, further suggesting that intimate mixing takes place between CE and XG. The resulting CE/XG films were found to be free of ionic liquid, transparent and with no evidence of phase separation at the micron scale. The mechanical properties of the blend with a CE:XG ratio close to one revealed a synergistic effect for which a maximum in the elongation and stress at break was observed in combination with a high elastic modulus. Atomic force microscopy indicates a co-continuous nanostructure for this composition. It is proposed that the non-monotonous variation of the mechanical performance of the films with XG content is due to this observed nanostructuration.

Complementary characterization data in support of uniaxially aligned electrospun nanocomposites based on a model PVOH-epoxy system.

This paper presents complementary data corresponding to characterization tests done for our research article entitled "Uniaxially aligned electrospun fibers for advanced nanocomposites based on a model PVOH-epoxy system" (Karimi et al., 2016) [1]. Poly(vinyl alcohol) and epoxy resin were selected as a model system and the effect of electrospun fiber loading on polymer properties was examined in conjunction with two manufacturing methods. A novel electrospinning technology for production of uniaxially aligned nanofiber arrays was used. A conventional wet lay-up fabrication method is compared against a novel, hybrid electrospinning-electrospraying approach. The structure and thermomechanical properties of resulting composite materials were examined using scanning electron microscopy, dynamic mechanical analysis, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, and tensile testing. For discussion of obtained results please refer to the research paper (Karimi et al., 2016) [1].

Topologically ordered magnesium-biopolymer hybrid composite structures.

Magnesium and its alloys are intriguing as possible biodegradable biomaterials due to their unique combination of biodegradability and high specific mechanical properties. However, uncontrolled biodegradation of magnesium during implantation remains a major challenge in spite of the use of alloying and protective coatings. In this study, a hybrid composite structure of magnesium metal and a biopolymer was fabricated as an alternative approach to control the corrosion rate of magnesium. A multistep process that combines metal foam production and injection molding was developed to create a hybrid composite structure that is topologically ordered in all three dimensions. Preliminary investigations of the mechanical properties and corrosion behavior exhibited by the hybrid Mg-polymer composite structures suggest a new potential approach to the development of Mg-based biomedical devices.

Magnesium biomaterials for orthopedic application: a review from a biological perspective.

Magnesium (Mg) has a long history of investigation as a degradable biomaterial. Physicians first began using Mg for biomedical applications in the late 19th century. Experimentation continued with varying levels of success until the mid-20th century when interest in the metal waned. In recent years the field of Mg-based biomaterials has once again become popular, likely due to advancements in technology allowing improved control of corrosion. Although this has led to success in vascular applications, continued difficulties in predicting and controlling the corrosion rate of Mg in an intraosseous environment has impeded the development of Mg-based biomaterials for orthopedic applications. In this review, an initial summary of the basic properties and the physiological role of Mg are followed by a discussion of the physical characteristics of the metal which lend it to use as a degradable biomaterial. A description of the historical and modern applications for Mg in the medical field is followed by a discussion of the methods used to control and assess Mg corrosion, with an emphasis on alloying. The second part of this review concentrates on the methods used to assess the corrosion and biocompatibility of Mg-based orthopedic biomaterials. This review provides a summary of Mg as a biomaterial from a biological perspective.

Monetite and brushite coated magnesium: in vivo and in vitro models for degradation analysis.

The use of magnesium (Mg) as a biodegradable metallic replacement of permanent orthopaedic materials is a current topic of interest and investigation. The appropriate biocompatibility, elastic modulus and mechanical properties of Mg recommend its suitability for bone fracture fixation. However, the degradation rates of Mg can be rapid and unpredictable resulting in mass hydrogen production and potential loss of mechanical integrity. Thus the application of calcium phosphate coatings has been considered as a means of improving the degradation properties of Mg. Brushite and monetite are utilized and their degradation properties (alongside uncoated Mg controls) are assessed in an in vivo subcutaneous environment and the findings compared to their in vitro degradation behaviour in immersion tests. The current findings suggest monetite coatings have significant degradation protective effects compared to brushite coatings in vivo. Furthermore, it is postulated that an in vitro immersion test may be used as a tentative predictor of in vivo subcutaneous degradation behavior of calcium phosphate coated and uncoated Mg.

Growth of calcium phosphates on magnesium substrates for corrosion control in biomedical applications via immersion techniques.

Magnesium (Mg) has been suggested as a revolutionary biodegradable replacement for current permanent metals used in orthopedic applications. Current investigations concentrate on the control of the corrosion rate to match bone healing. Calcium phosphate coatings have been a recent focus of these investigations through various coating protocols. Within this investigation, an in situ crystallization technique was utilized as an inexpensive and relatively simple method to produce a brushite and monetite coating on pure Mg. Coatings were characterized using energy dispersive spectroscopy, glancing angle X-ray diffraction and field emission scanning electron microscopy. Corrosion protection properties of the coatings were assessed in physiological buffers, Earles balanced salt solution, minimum essential media, and minimum essential media containing serum albumin, over a 4-week period. Using this novel coating protocol, our findings indicate brushite and monetite coated Mg to have significant corrosive protective effects when compared with its uncoated counterpart whilst maintaining high coating substrate adhesion, homogeneity, and reproducibility.

Magnesium alloys: predicting in vivo corrosion with in vitro immersion testing.

Magnesium (Mg) and its alloys have been proposed as degradable replacements to commonly used orthopedic biomaterials such as titanium alloys and stainless steel. However, the corrosion of Mg in a physiological environment remains a difficult characteristic to accurately assess with in vitro methods. The aim of this study was to identify a simple in vitro immersion test that could provide corrosion rates similar to those observed in vivo. Pure Mg and five alloys (AZ31, Mg-0.8Ca, Mg-1Zn, Mg-1Mn, Mg-1.34Ca-3Zn) were immersed in either Earle's balanced salt solution (EBSS), minimum essential medium (MEM), or MEM-containing 40 g/L bovine serum albumin (MEMp) for 7, 14, or 21 days before removal and assessment of corrosion by weight loss. This in vitro data was compared to in vivo corrosion rates of the same materials implanted in a subcutaneous environment in Lewis rats for equivalent time points. The results suggested that, for the alloys investigated, the EBSS buffered with sodium bicarbonate provides a rate of degradation comparable to those observed in vivo. In contrast, the addition of components such as (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) (HEPES), vitamins, amino acids, and albumin significantly increased corrosion rates. Based on these findings, it is proposed that with this in vitro protocol, immersion of Mg alloys in EBSS can be used as a predictor of in vivo corrosion.

Buffer-regulated biocorrosion of pure magnesium.

Magnesium (Mg) alloys are being actively investigated as potential load-bearing orthopaedic implant materials due to their biodegradability in vivo. With Mg biomaterials at an early stage in their development, the screening of alloy compositions for their biodegradation rate, and hence biocompatibility, is reliant on cost-effective in vitro methods. The use of a buffer to control pH during in vitro biodegradation is recognised as critically important as this seeks to mimic pH control as it occurs naturally in vivo. The two different types of in vitro buffer system available are based on either (i) zwitterionic organic compounds or (ii) carbonate buffers within a partial-CO(2) atmosphere. This study investigated the influence of the buffering system itself on the in vitro corrosion of Mg. It was found that the less realistic zwitterion-based buffer did not form the same corrosion layers as the carbonate buffer, and was potentially affecting the behaviour of the hydrated oxide layer that forms on Mg in all aqueous environments. Consequently it was recommended that Mg in vitro experiments use the more biorealistic carbonate buffering system when possible.

Amyloid fibrils as functionalizable components of nanocomposite materials.

Amyloid fibrils are a form of protein nanofiber that show promise as components of multifunctional bionanomaterials. In this work, native bovine insulin and bovine insulin that had been previously converted into amyloid fibrils were combined with poly(vinyl alcohol) (PVOH) via solution casting to determine the effect of fibrillization on the thermomechanical properties of the resulting composite. The synthesis method was found to preserve the amyloid fibril structure and properties of the resulting fibril-PVOH composite were investigated. At a filling level of 0.6 wt %, the fibril-reinforced PVOH was 15% stiffer than the PVOH control. Various properties of the films, including the glass transition temperature, degradation temperature, microstructure, and film morphology were characterized. Although more work is required to optimize the properties of the composites, this study provides proof of principle that incorporation of amyloid fibrils into a polymeric material can impart useful changes to the mechanical and morphological properties of the films.

Solvent infusion processing of all-cellulose composite materials.

Continuous fibre-reinforced all-cellulose composite (ACC) laminates were produced in the form of a dimensionally thick (>1 mm) laminate using an easy-to-use processing pathway termed solvent infusion processing (SIP) from a rayon (Cordenka™) textile using the ionic liquid 1-butyl-3-methylimidazolium acetate. SIP facilitates the infusion of a solvent through a dry cellulose fibre preform with the aim of partially dissolving the outer surface of the cellulose fibres. The dissolved cellulose is then regenerated by solvent exchange to form a matrix phase in situ that acts to bond together the undissolved portion of the fibres. SIP is capable of producing thick, dimensionally stable ACC laminates with high volume fractions of continuous fibres (>70 vol.%) due to the combination of two factors: (i) homogeneous and controlled partial dissolution of the fibres and (ii) the application of pressure during regeneration and drying that provides a high level of fibre compaction, thereby overcoming void formation associated with material shrinkage. The effect of inlet and outlet positioning, and applied pressure on the macro- and microstructure of all-cellulose composites is examined. Finally, SIP expands the applications for ACCs by enabling the production of thick ACC laminates to overcome the limitations of conventional thin-film ACCs.

Dynamic mechanical analysis and biomineralization of hyaluronan-polyethylene copolymers for potential use in osteochondral defect repair.

Treatment options for damaged articular cartilage are limited due to its lack of vasculature and its unique viscoelastic properties. This study was the first to fabricate a hyaluronan (HA)-polyethylene copolymer for potential use in the replacement of articular cartilage and repair of osteochondral defects. Amphiphilic graft copolymers consisting of HA and high-density polyethylene (HA-co-HDPE) were fabricated with 10, 28 and 50 wt.% HA. Dynamic mechanical analysis was used to assess the effect of varying constituent weight ratios on the viscoelastic properties of HA-co-HDPE materials. The storage moduli of HA-co-HDPE copolymers ranged from 2.4 to 15.0 MPa at physiological loading frequencies. The viscoelastic properties of the HA-co-HDPE materials were significantly affected by varying the wt.% of HA and/or crosslinking of the HA constituent. Cytotoxicity and the ability of the materials to support mineralization were evaluated in the presence of bone marrow stromal cells. HA-co-HDPE materials were non-cytotoxic, and calcium and phosphorus were present on the surface of the HA-co-HDPE materials 2 weeks after osteogenic differentiation of the bone marrow stromal cells. This study is the first to measure the viscoelastic properties and osseocompatibility of HA-co-HDPE for potential use in orthopedic applications.

In-vitro dissolution of magnesium-calcium binary alloys: clarifying the unique role of calcium additions in bioresorbable magnesium implant alloys.

A systematic investigation of a series of magnesium-calcium binary alloys is presented to reveal the influence of increasing calcium (Ca) additions on the in vitro degradation of magnesium (Mg). Because of its prevalence in structural tissues, Ca is among the most biologically viable additions to orthopedic-intended Mg-based biomaterials. Hence, a fundamental electrochemical study of Ca additions to Mg biomaterials is essential to its continued role as an alloying addition. In this work, in vitro degradation conditions closer to the physiological environment were implemented through the addition of proteins to simulated body fluid and maintenance of a constant pH, with tests conducted using Hanks solution, minimum essential medium (MEM), and MEM containing fetal bovine serum. Alloying with Ca leads to the formation of Mg2Ca intermetallic particles that result in systematically enhanced dissolution kinetics. This observation is rationalized via microelectrochemical tests upon the Mg2Ca intermetallic in isolation, which reveals rapid anodic kinetics. Hence, the extent of Mg-Ca alloy dissolution can be modified depending on the amount of Mg2Ca present, suggesting that Ca can be deployed as a functional addition capable of not only enhancing biodissolution of the alloy, but being able to do this in a systematic, controllable manner depending on its volume fraction. In addition, up to a 3-fold reduction in the corrosion rate is observed with corrosion testing in an albumin-containing medium when compared to Hanks solution, the results highlighting that the use of a physiologically "correct" medium is essential for the in vitro screening of Mg-based alloys suitable for orthopaedic applications.

Electrospun single-walled carbon nanotube/polyvinyl alcohol composite nanofibers: structure-property relationships.

Polyvinyl alcohol (PVA) nanofibers and single-walled carbon nanotube (SWNT)/PVA composite nanofibers have been produced by electrospinning. An apparent increase in the PVA crystallinity with a concomitant change in its main crystalline phase and a reduction in the crystalline domain size were observed in the SWNT/PVA composite nanofibers, indicating the occurrence of a SWNT-induced nucleation crystallization of the PVA phase. Both the pure PVA and SWNT/PVA composite nanofibers were subjected to the following post-electrospinning treatments: (i) soaking in methanol to increase the PVA crystallinity, and (ii) cross-linking with glutaric dialdehyde to control the PVA morphology. Effects of the PVA morphology on the tensile properties of the resultant electrospun nanofibers were examined. Dynamic mechanical thermal analyses of both pure PVA and SWNT/PVA composite electrospun nanofibers indicated that SWNT-polymer interaction facilitated the formation of crystalline domains, which can be further enhanced by soaking the nanofiber in methanol and/or cross-linking the polymer with glutaric dialdehyde.

Bone-like matrix formation on magnesium and magnesium alloys.

Mg metal and its alloys have promise as a biocompatible, degradable biomaterials. This work evaluates the potential of in vitro cell culture work with osteoblast-like cells on Mg based materials, and investigates cell differentiation and growth on Mg alloyed with various non-toxic or low-toxicity elements. Mg based substrates support the adhesion, differentiation and growth of stromal cells towards an osteoblast-like phenotype with the subsequent production of a bone like matrix under in vitro conditions. No significant difference in the final tissue layer is observed on pure Mg, an AZ21 alloy or a 0.5 wt% Ca alloy. Only a 0.8 wt% Ca alloy which shows complete structural disintegration shows minimal cell growth. Due to association of non-soluble degradation products formed when Mg is incubated in physiological-like fluid, mass changes typically used to report Mg degradation are not viable estimates of degradation. Methods quantifying the time dependent change in the mechanical integrity of samples as a function of incubation time are required for a proper assessment of Mg degradation. We conclude that in vitro cell culture of bone cells on Mg substrates is expected to be a viable screening technique to assess the relative biological activity of Mg-based materials.

Magnesium and its alloys as orthopedic biomaterials: a review.

As a lightweight metal with mechanical properties similar to natural bone, a natural ionic presence with significant functional roles in biological systems, and in vivo degradation via corrosion in the electrolytic environment of the body, magnesium-based implants have the potential to serve as biocompatible, osteoconductive, degradable implants for load-bearing applications. This review explores the properties, biological performance, challenges and future directions of magnesium-based biomaterials.