Mass customization of medical devices and implants: state of the art and future directions

The medical field is one in which the need for customization can be clear cut, as providing tailored devices and implants for unique physiologies can provide for a better overall treatment than the use of ‘off the shelf’ devices and implants. Customization in the production of medical products can be roughly divided into consideration of medical devices, and of implantable parts or systems. The present paper outlines the current state of the art in both of these areas, presents details of projects that are ongoing at the University of Leeds and outlines future research directions.     

An investigation into the flexural characteristics of functionally graded cobalt chrome femoral stems manufactured using selective laser melting

In order to reduce the stress shielding of the femur following Total Hip Arthroplasty (THA), stiffness matching strategies between the host bone and femoral stem still need to be investigated. Additive Layer Manufacturing (ALM) technologies such as Selective Laser Melting (SLM) can produce components from a single alloy with varying mechanical properties, and hence, functionally graded parts. This work considers the flexural characteristics of laser melted cobalt chrome femoral stems, by using a combination of mechanical testing and finite element analysis. A functionally graded design methodology was considered in order to reduce the weight and stiffness of the femoral stems. Three separate functionally graded designs were investigated by incorporating square pore cellular structures of varying density. The results confirmed that selective laser melting can repeatedly manufacture a functionally graded femoral stem that is 48% lighter and 60% more flexible than a traditional fully dense stem. However, there are concerns associated with the repeatability of the manufacturing process for producing stems with cellular structures that incorporate strut sizes, which are equal to or less than 0.5 mm.     

Rotary scanning wireless temperature measurement method for hyperthermia using ferromagnetic implants

Recently, the use of a ferromagnetic material in a soft‐heating method has garnered much attention as a novel method for cancer treatment. By concurrently using this material as a thermal probe, we are currently developing a minimally invasive heating and wireless temperature measurement system. To make the approach feasible in a clinical setting, it is vital to overcome the key challenge of heating the local tumor at a constant temperature. In previous conventional approaches, it was necessary to switch the induction‐heating power supply on/off after the target tumor temperature was reached. However, it cannot determine the temperature of the material during the power‐off period. Therefore, we changed this approach and found that by adjusting the distance between the heating coil and the material while maintaining a constant current flow in heating coil, the drift problem, which happened just after power is supplied during the on/off operation, did not occur any longer. Accordingly, it was not required to use multiple sensors to reduce the drift, thereby minimizing the cost. This study verifies the validity of our wireless thermometry approach while performing rotary scanning and proposes a technique for determining achievement of the target temperature. This knowledge complements other approaches for cancer treatment utilizing hyperthermia. © 2015 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.     

Titanium diffusion in shinbone of rats with osseointegrated implants

Dental implants are composed of commercially pure Ti (which is actually an alloy of titanium, and minor or trace components such as aluminium and vanadium). When the implant is inserted, its surface undergoes a number of chemical and mechanical processes, releasing particles of titanium to the medium. The metabolism of free ions of titanium is uncertain; the uptaking processes in the body are not well known, nor their toxic dose. In addition, physical properties of newly formed bone, such as diffusivity and activation energy, are scarce and rarely studied. In this study, we analysed the diffusion of titanium in the titanium‐implanted shinbones of six adult male Wistar rats by spatially resolved micro x‐ray fluorescence. The measurements were carried out at the microfluorescence station of the x‐ray fluorescence (XRF) beamline of the Brazilian synchrotron facility LNLS (from Portuguese ‘Laboratorio Nacional de Luz Sincrotron’). For each sample, XRF spectra were taken by linear scanning in area near the new bone formed around the Ti implant. The scanning line shows a clear effect of titanium diffusion whereas calcium intensity presents a different behaviour. Moreover, a clear correlation among the different structures of bones is observed in the Ti and Ca intensities. The results obtained in these measurements may allow determining quantitatively the parameters of diffusion rates and other physical properties of new bone like diffusion coefficients.     

聚醚醚酮骨植入体生物改性研究进展

聚醚醚酮是一种热塑性材料,凭其良好的生物相容性和X射线可透射性,被广泛用于生物医学领域。而PEEK骨植入体与人体骨骼强度存在一定差距,与人体骨组织结合能力较差和抗菌性能等不足,使其在生物领域的应用受到了限制。为了使PEEK更好地应用于人体骨植入领域,获得优异生物性能的PEEK骨植入体已成为研究的重点。概述了PEEK的加工技术、力学性能、骨整合性能和抗菌性能的研究。在此基础上,重点综述了近年来提高PEEK骨植入体力学性能与生物性能的各种改性方法的研究进展。在力学性能方面,对PEEK常用的填充材料碳纤维进行了概述,由于PEEK与碳纤维界面结合强度影响其整体力学性能,重点介绍了提高其结合强度的改性方法。在骨整合性能方面,对钛、二氧化钛和羟基磷灰石涂层材料及喷涂方法进行了概述,以及对等离子喷涂、喷砂、激光蚀刻和浓硫酸刻蚀表面处理方法的优缺点进行了分析。在抗菌性能方面,银离子释放浓度过高时会导致细胞毒性,重点阐述了如何控制银离子释放速度的研究。最后展望了PEEK骨植入体加工和改性的未来发展方向。     

医用钛植入体激光微纹理生物性能研究进展

医用钛合金具有强度高、弹性模量低、疲劳性能好、密度最接近人骨等优点,被广泛应用于临床医学牙科和骨移植等领域。目前较常用的医用钛合金表面加工方法包括机械加工、酸蚀、喷砂、等离子喷涂和激光加工等。通过对比分析,激光加工表现出明显优势,与化学或传统物理加工方法相比,采用激光加工医用钛植入体表面具有高效、清洁、准确、柔性等优势。应用各类脉冲激光器,可以在植入体表面加工特定的表面纹理和纹理组合,改善植入体的生物相容性。归纳了植入体表面纹理对植入环境的影响,表面纹理形状、粗糙度和润湿性等表面特性直接影响细胞组织的黏附、生长和增殖,对细胞生长具有接触导向作用。通过调控激光通量、脉冲频率、扫描速度和脉冲宽度等激光参量可对表面纹理的规则性、准确性、尺寸、氧化程度等特征产生不同影响,进而影响医用钛植入体的表面微观形貌、粗糙度、硬度和润湿性,使其在生物环境中获得更好的服役性能。通过激光加工获得的理想医用钛植入体表面可有效避免植入体表面细菌的滋生,降低发病率,提高植入成功率。经激光加工后,医用钛植入体表面会出现不同程度的裂纹,导致在服役过程中植入体表面产生的摩擦碎屑对植入体环境造成不良影响。通过综述以上各方面的研究进展可知,随着超短脉冲激光技术的发展和新型医用植入体材料β钛合金制备技术与工艺的完善,经激光加工后植入体将获得更理想的表面特性和服役性能。     

Electrophoretic deposition of bioactive glass nanopowders on magnesium based alloy for biomedical applications

To slow down the initial biodegradation rate of magnesium (Mg) alloy, crystalline nano-sized bioactive glass coating was used to deposit on micro-arc oxidized AZ91 samples via electrophoretic deposition (EPD). Zeta potential and conductivity of the bioactive glass suspension were characterized at various pH values to identify the most stable dispersion conditions. The bone-bonding properties of bioactive glass coated samples were evaluated in terms of apatite-forming ability during the immersion in simulated body fluid (SBF) solution. Results revealed that the ability to form a bioactive glass coating via EPD was influenced by the degree of its crystalline phase composition. Moreover, the potentiodynamic polarization tests recorded significant drops in corrosion current density and corrosion rate of the coated samples which implies a good level of corrosion protective behavior. These preliminary results show that this process will enable the development of Mg implants in the later stage of bone healing.     

Facilitating GL13K Peptide Grafting on Polyetheretherketone via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide: Surface Properties and Antibacterial Activity

In the present work, the antimicrobial peptide (AMP) of GL13K was successfully coated onto a polyetheretherketone (PEEK) substrate to investigate its antibacterial activities against Staphylococcus aureus (S. aureus) bacteria. To improve the coating efficiency, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) was mixed with a GL13K solution and coated on the PEEK surface for comparison. Both energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) data confirmed 30% greater peptide coating on PEEK/GL13K-EDC than PEEK without EDC treatment. The GL13K graft levels are depicted in the micrograms per square centimeter range. The PEEK/GL13K-EDC sample showed a smoother and lower roughness (Rq of 0.530 µm) than the PEEK/GL13K (0.634 µm) and PEEK (0.697 µm) samples. The surface of the PEEK/GL13K-EDC was more hydrophilic (with a water contact angle of 24°) than the PEEK/GL13K (40°) and pure PEEK (89°) samples. The pure PEEK disc did not exhibit any inhibition zone against S. aureus. After peptide coating, the samples demonstrated significant zones of inhibition: 28 mm and 25 mm for the PEEK/GL13K-EDC and PEEK/GL13K samples, respectively. The bacteria-challenged PEEK sample showed numerous bacteria clusters, whereas PEEK/GL13K contained a little bacteria and PEEK/GL13K-EDC had no bacterial attachment. The results confirm that the GL13K peptide coating was able to induce antibacterial and biofilm-inhibitory effects. To the best of our knowledge, this is the first report of successful GL13K peptide grafting on a PEEK substrate via EDC coupling. The present work illustrates a facile and promising coating technique for a polymeric surface to provide bactericidal activity and biofilm resistance to medical implantable devices.     

Healing Pattern Analysis for Dental Implants Using the Mechano-Regulatory Tissue Differentiation Model

(1) Background: Our aim is to reveal the influence of the geometry designs on biophysical stimuli and healing patterns. The design guidelines for dental implants can then be provided. (2) Methods: A two-dimensional axisymmetric finite element model was developed based on mechano-regulatory algorithm. The history of tissue differentiation around eight selected implants can be predicted. The performance of the implants was evaluated by bone area (BA), bone-implant contact (BIC); (3) Results: The predicted healing patterns have very good agreement with the experimental observation. Many features observed in literature, such as soft tissues covering on the bone-implant interface; crestal bone loss; the location of bone resorption bumps, were reproduced by the model and explained by analyzing the solid and fluid biophysical stimuli and (4) Conclusions: The results suggested the suitable depth, the steeper slope of the upper flanks, and flat roots of healing chambers can improve the bone ingrowth and osseointegration. The mechanism related to solid and fluid biophysical stimuli were revealed. In addition, the model developed here is efficient, accurate and ready to extend to any geometry of dental implants. It has potential to be used as a clinical application for instant prediction/evaluation of the performance of dental implants.     

Monoolein–Water Liquid Crystalline Gels of Gentamicin as Bioresorbable Implants for the Local Treatment of Chronic Osteomyelitis: In Vitro Characterization

To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic systemic toxicity, as well as time and costs of hospitalizations, it has been thought that monoolein–water gels incorporating gentamicin sulfate could be used as local, bioresorbable, and sustained-release implants. For this purpose, four formulations were examined with regard to their physicochemical and in vitro drug release characteristics. Hot stage microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction showed cubic liquid crystalline and eutectic structures. The more suitable formulation consisting of 80–15–5% wt/wt monoolein–water–gentamicin sulfate progressively released the antibiotic for a period of 3 weeks without burst effect. Moreover, the content and the release profile of gentamicin sulfate were not significantly changed after storage at 2–6°C for a period of 10 months.