Clinical utility of the KAMRA corneal inlay

The treatment of presbyopia has been the focus of much scientific and clinical research over recent years, not least due to an increasingly aging population but also the desire for spectacle independence. Many lens and nonlens-based approaches have been investigated, and with advances in biomaterials and improved surgical methods, removable corneal inlays have been developed. One such development is the KAMRA™ inlay where a small entrance pupil is exploited to create a pinhole-type effect that increases the depth of focus and enables improvement in near visual acuity. Short- and long-term clinical studies have all reported significant improvement in near and intermediate vision compared to preoperative measures following monocular implantation (nondominant eye), with a large proportion of patients achieving Jaeger (J) 2 to J1 (~0.00 logMAR to ~0.10 logMAR) at the final follow-up. Although distance acuity is reduced slightly in the treated eye, binocular visual acuity and function remain very good (mean 0.10 logMAR or better). The safety of the inlay is well established and easily removable, and although some patients have developed corneal changes, these are clinically insignificant and the incidence appears to reduce markedly with advancements in KAMRA design, implantation technique, and femtosecond laser technology. This review aims to summarize the currently published peer-reviewed studies on the safety and efficacy of the KAMRA inlay and discusses the surgical and clinical outcomes with respect to the patient’s visual function.

Wound healing studies and interfacial phenomena:use and relevance of the corneal model

The interaction of the wound dressing as a biomaterial with the wound bed is the central issue of this chapter. The interfacial phenomenon that encompasses the biological and biochemical consequences that arise when a biomaterial is introduced to a host biological environment is discussed. A great deal can be learned from observations arising from the behaviour of biomaterials at other body sites; one particularly relevant body site in the context of wound healing is the anterior eye. The cornea, tear film and posterior surface of the contact lens provide an informative model of the parallel interface that exists between the chronic wound bed, wound fluid and the dressing biomaterial. © 2011 Woodhead Publishing Limited All rights reserved.

Physicochemical properties of hydrogels for use in ophthalmology

This chapter deals with the physicochemical aspects of structure-property relationships in synthetic hydrogels, with particular reference to their application in optometry and ophthalmology. It demonstrates the ways in which the amount of water contained in the hydrogel network can be manipulated by changes in copolymer composition and illustrates the advantages and limitations imposed by use of water as a means of influencing surface, transport and mechanical properties of the gel. The chapter then illustrates how this basic understanding has formed a platform for the development of synthetic interpenetrating networks and macroporous materials, and of hybrids of natural and synthetic hydrogels. The behaviour of these more complex systems is not so centrally dominated by the equilibrium water content as is the case with homogeneous synthetic hydrogels, thus providing advantageous ways of extending the properties and applications of these interesting materials.

Ocular biotribology and the contact lens:Surface interactions and ocular response

Biotribology is essentially the study of friction, lubrication and wear in biological systems. The area has been widely studied in relation to the behaviour of synovial joints and the design and behaviour of hip joint prostheses, but only in the last decade have serious studies been extended to the eye. In the ocular environment - as distinct from articular joints - wear is not a major factor. Both lubrication and friction are extremely important, however; this is particularly the case in the presence of the contact lens, which is a medical device important not only in vision correction but also as a therapeutic bandage for the compromised cornea. This chapter describes the difficulty in replicating experimental conditions that accurately reflect the complex nature of the ocular environment together with the factors such as load and rate of travel of the eyelid, which is the principal moving surface in the eye. Results obtained across a range of laboratories are compared.

Design and performance assessment of aortic heart valve for tissue engineering

Current artificial heart valves are classified as mechanical and bioprosthetic. An appealing pathway that promises to overcome the shortcomings of commercially available heart valves is offered by the interdisciplinary approach of cardiovascular tissue engineering. However, the mechanical properties of the Tissue Engineering Heart Valves (TEHV) are limited and generally fail in the long-term use. To meet this performance challenge novel biodegradable triblock copolymer poly(ethylene oxide)-polypropylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO or F108) crosslinked to Silk Fibroin (F108-SilkC) to be used as tri-leaflet heart valve material was investigated. ^ Synthesis of ten polymers with varying concentration and thickness (55 µm, 75 µm and 100 µm) was achieved via a covalent crosslinking scheme using bifunctional polyethylene glycol diglycidyl ether (PEGDE). Static and fatigue testing were used to assess mechanical properties of films, and hydrodynamic testing was performed to determine performance under a simulated left ventricular flow regime. The crosslinked copolymer (F108-Silk C) showed greater flexibility and resilience, but inferior ultimate tensile strength, by increasing concentration of PEGDE. Concentration molar ratio of 80:1 (F108: Silk) and thickness of 75 µm showed longer fatigue life for both tension-tension and bending fatigue tests. Four valves out of twelve designed satisfactorily complied with minimum performance requirement ISO 5840, 2005. ^ In conclusion, it was demonstrated that the applicability of a degradable polymer in conjugation with silk fibroin for tissue engineering cardiovascular use, specifically for aortic valve leaflet design, met the performance demands. Thinner thicknesses (t<75 µm) in conjunction with stiffness lower than 320 MPa (80:1, F108: Silk) are essential for the correct functionality of proposed heart valve biomaterial F108-SilkC. Fatigue tests were demonstrated to be a useful tool to characterize biomaterials that undergo cyclic loading. ^

Assessment of biodegradable magnesium alloys for enhanced mechanical and biocompatible properties

Biomaterials have been used for more than a century in the human body to improve body functions and replace damaged tissues. Currently approved and commonly used metallic biomaterials such as, stainless steel, titanium, cobalt chromium and other alloys have been found to have adverse effects leading in some cases, to mechanical failure and rejection of the implant. The physical or chemical nature of the degradation products of some implants initiates an adverse foreign body reaction in the tissue. Some metallic implants remain as permanent fixtures, whereas others such as plates, screws and pins used to secure serious fractures are removed by a second surgical procedure after the tissue has healed sufficiently. However, repeat surgical procedures increase the cost of health care and the possibility of patient morbidity. This study focuses on the development of magnesium based biodegradable alloys/metal matrix composites (MMCs) for orthopedic and cardiovascular applications. The Mg alloys/MMCs possessed good mechanical properties and biocompatible properties. Nine different compositions of Mg alloys/MMCs were manufactured and surface treated. Their degradation behavior, ion leaching, wettability, morphology, cytotoxicity and mechanical properties were determined. Alloying with Zn, Ca, HA and Gd and surface treatment resulted in improved mechanical properties, corrosion resistance, reduced cytotoxicity, lower pH and hydrogen evolution. Anodization resulted in the formation of a distinct oxide layer (thickness 5-10 μm) as compared with that produced on mechanically polished samples (~20-50 nm) under ambient conditions. It is envisaged that the findings of this research will introduce a new class of Mg based biodegradable alloys/MMCs and the emergence of innovative cardiovascular and orthopedic implant devices.^

An assessment of novel biodegradable magnesium alloys for endovascular biomaterial applications

Magnesium alloys have been widely explored as potential biomaterials, but several limitations to using these materials have prevented their widespread use, such as uncontrollable degradation kinetics which alter their mechanical properties. In an attempt to further the applicability of magnesium and its alloys for biomedical purposes, two novel magnesium alloys Mg-Zn-Cu and Mg-Zn-Se were developed with the expectation of improving upon the unfavorable qualities shown by similar magnesium based materials that have previously been explored. The overall performance of these novel magnesium alloys has been assessesed in three distinct phases of research: 1) analysing the mechanical properties of the as-cast magnesium alloys, 2) evaluating the biocompatibility of the as-cast magnesium alloys through the use of in-vitro cellular studies, and 3) profiling the degradation kinetics of the as-cast magnesium alloys through the use of electrochemical potentiodynamic polarization techqnique as well as gravimetric weight-loss methods. As compared to currently available shape memory alloys and degradable as-cast alloys, these experimental alloys possess superior as-cast mechanical properties with elongation at failure values of 12% and 13% for the Mg-Zn-Se and Mg-Zn-Se alloys, respectively. This is substantially higher than other as-cast magnesium alloys that have elongation at failure values that range from 7-10%. Biocompatibility tests revealed that both the Mg-Zn-Se and Mg-Zn-Cu alloys exhibit low cytotoxicity levels which are suitable for biomaterial applications. Gravimetric and electrochemical testing was indicative of the weight loss and initial corrosion behavior of the alloys once immersed within a simulated body fluid. The development of these novel as-cast magnesium alloys provide an advancement to the field of degradable metallic materials, while experimental results indicate their potential as cost-effective medical devices.^

Fiber Scaffolds of Poly (glycerol-dodecanedioate) and its Derivative via Electrospinning for Neural Tissue Engineering

Peripheral nerves have demonstrated the ability to bridge gaps of up to 6 mm. Peripheral Nerve System injury sites beyond this range need autograft or allograft surgery. Central Nerve System cells do not allow spontaneous regeneration due to the intrinsic environmental inhibition. Although stem cell therapy seems to be a promising approach towards nerve repair, it is essential to use the distinct three-dimensional architecture of a cell scaffold with proper biomolecule embedding in order to ensure that the local environment can be controlled well enough for growth and survival. Many approaches have been developed for the fabrication of 3D scaffolds, and more recently, fiber-based scaffolds produced via the electrospinning have been garnering increasing interest, as it offers the opportunity for control over fiber composition, as well as fiber mesh porosity using a relatively simple experimental setup. All these attributes make electrospun fibers a new class of promising scaffolds for neural tissue engineering. Therefore, the purpose of this doctoral study is to investigate the use of the novel material PGD and its derivative PGDF for obtaining fiber scaffolds using the electrospinning. The performance of these scaffolds, combined with neural lineage cells derived from ESCs, was evaluated by the dissolvability test, Raman spectroscopy, cell viability assay, real time PCR, Immunocytochemistry, extracellular electrophysiology, etc. The newly designed collector makes it possible to easily obtain fibers with adequate length and integrity. The utilization of a solvent like ethanol and water for electrospinning of fibrous scaffolds provides a potentially less toxic and more biocompatible fabrication method. Cell viability testing demonstrated that the addition of gelatin leads to significant improvement of cell proliferation on the scaffolds. Both real time PCR and Immunocytochemistry analysis indicated that motor neuron differentiation was achieved through the high motor neuron gene expression using the metabolites approach. The addition of Fumaric acid into fiber scaffolds further promoted the differentiation. Based on the results, this newly fabricated electrospun fiber scaffold, combined with neural lineage cells, provides a potential alternate strategy for nerve injury repair.

An Investigation on Biocompatibility of Bio-Absorbable Polymer Coated Magnesium Alloys

Advances in biomaterials have enabled medical practitioners to replace diseased body parts or to assist in the healing process. In situations where a permanent biomaterial implant is used for a temporary application, additional surgeries are required to remove these implants once the healing process is complete, which increases medical costs and patient morbidity. Bio-absorbable materials dissolve and are metabolized by the body after the healing process is complete thereby negating additional surgeries for removal of implants. Magnesium alloys as novel bio-absorbable biomaterials, have attracted great attention recently because of their good mechanical properties, biocompatibility and corrosion rate in physiological environments. However, usage of Mg as biodegradable implant has been limited by its poor corrosion resistance in the physiological solutions. An optimal biodegradable implant must initially have slow degradation to ensure total mechanical integrity then degrade over time as the tissue heals. The current research focuses on surface modification of Mg alloy (MZC) by surface treatment and polymer coating in an effort to enhance the corrosion rate and biocompatibility. It is envisaged that the results obtained from this investigation would provide the academic community with insights for the utilization of bio-absorbable implants particularly for patients suffering from atherosclerosis. The alloying elements used in this study are zinc and calcium both of which are essential minerals in the human metabolic and healing processes. A hydrophobic biodegradable co-polymer, polyglycolic-co-caprolactone (PGCL), was used to coat the surface treated MZC to retard the initial degradation rate. Two surface treatments were selected: (a) acid etching and (b) anodization to produce different surface morphologies, roughness, surface energy, chemistry and hydrophobicity that are pivotal for PGCL adhesion onto the MZC. Additionally, analyses of biodegradation, biocompatibility, and mechanical integrity were performed in order to investigate the optimum surface modification process, suitable for biomaterial implants. The study concluded that anodization created better adhesion between the MZC and PGCL coating. Furthermore, PGCL coated anodized MZC exhibited lower corrosion rate, good mechanical integrity, and better biocompatibility as compared with acid etched.

In-Vivo Corrosion and Fretting of Modular TI-6AL-4V/CO-CR-MO Hip Prostheses: The Influence of Microstructure and Design Parameters

The purpose of this study was to evaluate the incidence of corrosion and fretting in 48 retrieved titanium-6aluminum-4vanadium and/or cobalt-chromium-molybdenum modular total hip prosthesis with respect to alloy material microstructure and design parameters. The results revealed vastly different performance results for the wide array of microstructures examined. Severe corrosion/fretting was seen in 100% of as-cast, 24% of low carbon wrought, 9% of high carbon wrought and 5% of solution heat treated cobalt-chrome. Severe corrosion/fretting was observed in 60% of Ti-6Al-4V components. Design features which allow for fluid entry and stagnation, amplification of contact pressure and/or increased micromotion were also shown to play a role. 75% of prosthesis with high femoral head-trunnion offset exhibited poor performance compared to 15% with a low offset. Large femoral heads (>32mm) did not exhibit poor corrosion or fretting. Implantation time was not sufficient to cause poor performance; 54% of prosthesis with greater than 10 years in-vivo demonstrated none or mild corrosion/fretting.

Preparação e caracterização de biomateriais poliméricos para avaliação da viabilidade de uso como phantom biológico

The theoretical and experimental developments in the biomaterials area have been directly applied to different fields of Medicine (odontology, regenerative medicine and radiotherapy). These advances have focused both for diagnosing diseases such as for quantifying degrees of progression. From the perspective of these studies, biomaterials are being designed and manufactured for application in various areas of science, provided advances in diagnostic radiology, radiotherapy dosimetry and calibration of radiotherapy equipment. Develop a phantom from a biomaterial has become a great ally of medicine in the treat patients with oncological diseases, allowing better performance of the equipment in order to reduce damage to healthy tissue due to excessive exposure to radiation. This work used polymers: chitosan and gelatin, for making the polymeric structures and controlled for different types of production and processing, characterizing and evaluating the biopolymer by physical techniques (STL, SEM and DEI) and therefore analyze applicability as phantom mouse lung. It was possible to evaluate the morphology of biomaterials quantitatively by scanning electron microscopy associated with imaging technique. The relevance of this work focuses on developing a phantom from polymeric biomaterials that can act as phantom providing high image contrast when subjected to analysis. Thus, the choice of DEI technique is satisfactory since it is an imaging technique of X-ray high resolution. The images obtained by DEI have shown the details of the internal microstructure of the biomaterial produced which have ≈ 10 μm dimension. The phantoms had made density ranging from 0.08 a 0.13 g/cm3.

Fibrillar Elastomeric Micropatterns Create Tunable Adhesion Even to Rough Surfaces

Acknowledgements V.B., N.K.G., and E.A. contributed with conception and experimental design. V.B. performed the experiments. V.B., R.H., A.G., and R.M.M. carried out analysis and interpretation of data. V.B., R.H., A.G., and E.A. wrote the manuscript. V.B. and R.H. contributed equally to this work. V.B. acknowledges funding by SPP 1420 of the German Science Foundation DFG. E.A., N.K.G., and R.H. acknowledge funding from the European Research Council under the European Union/ERC Advanced Grant “Switch2Stick,” Agreement No. 340929.

The application of 3D printing to study microfluidic architecture for 'on-chip' mixing systems for SRCD and UV spectroscopy

This paper details methodologies that have been explored for the fast proofing of on-chip architectures for Circular Dichroism techniques. Flow-cell devices fabricated from UV transparent Quartz are used for these experiments. The complexity of flow-cell production typically results in lead times of six months from order to delivery. Only at that point can the on-chip architecture be tested empirically and any required modifications determined ready for the next six month iteration phase. By using the proposed 3D printing and PDMS moulding techniques for fast proofing on-chip architectures the optimum design can be determined within a matter of hours prior to commitment to quartz chip production.

The development of an automated nano sampling handling system for nanometre protein crystallography experiments

As the world's synchrotrons and X-FELs endeavour to meet the need to analyse ever-smaller protein crystals, there grows a requirement for a new technique to present nano-dimensional samples to the beam for X-ray diffraction experiments.The work presented here details developmental work to reconfigure the nano tweezer technology developed by Optofluidics (PA, USA) for the trapping of nano dimensional protein crystals for X-ray crystallography experiments. The system in its standard configuration is used to trap nano particles for optical microscopy. It uses silicon nitride laser waveguides that bridge a micro fluidic channel. These waveguides contain 180 nm apertures of enabling the system to use biologically compatible 1.6 micron wavelength laser light to trap nano dimensional biological samples. Using conventional laser tweezers, the wavelength required to trap such nano dimensional samples would destroy them. The system in its optical configuration has trapped protein molecules as small as 10 nanometres.

The automation of protein crystal presentation for x ray diffraction experiments using standing acoustic waves in a microfluidic chip environment

As the pressure continues to grow on Diamond and the world's synchrotrons for higher throughput of diffraction experiments, new and novel techniques are required for presenting micron dimension crystals to the X ray beam. Currently this task is both labour intensive and primarily a serial process. Diffraction measurements typically take milliseconds but sample preparation and presentation can reduce throughput down to 4 measurements an hour. With beamline waiting times as long as two years it is of key importance for researchers to capitalize on available beam time, generating as much data as possible. Other approaches detailed in the literature [1] [2] [3] are very much skewed towards automating, with robotics, the actions of a human protocols. The work detailed here is the development and discussion of a bottom up approach relying on SSAW self assembly, including material selection, microfluidic integration and tuning of the acoustic cavity to order the protein crystals.