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OBJECTIVES While decellularization has previously significantly improved the durability of bioprosthetic tissue, remnant immunogenicity may yet necessitate masking through crosslinking. To alleviate the fears of reintroducing the risk of calcific degeneration, we investigated the application of rationally designed crosslinking chemistry, capable of abrogating mineralization in isolation, in decellularized tissue. METHODS Bovine and porcine pericardium were decellularized using the standard Triton X/sodium deoxycholate/DNAse/RNAse methodology and thereafter combined incrementally with components of a four-stage high-density dialdehyde-based fixation regimen. Mechanical properties prior to, and calcium levels following, subcutaneous implantation for 6 and 10 weeks in rats were assessed. RESULTS Enhanced four-stage crosslinking, independent of decellularization, or decellularization followed by any of the crosslinking regimens, achieved sustained, near-elimination of tissue calcification. Decellularization additionally resulted in significantly lower tissue stiffness and higher fatigue resistance in all groups compared to their non-decellularized counterparts. CONCLUSIONS The dual approach of combining decellularization with enhanced crosslinking chemistry in xenogeneic pericardial tissue offers much promise in extending bioprosthetic heart valve longevity.

Background/AimTo assess visual acuity (VA) outcomes and antivascular endothelial growth factor (anti-VEGF) treatment intensity in diabetic macular oedema (DMO).MethodsRetrospective analysis was performed in treatment-naïve patients with DMO from 2013 to 2018 using a database of aggregated de-identified electronic medical records (Vestrum Health).ResultsAt 1 year, 28 658 patient eyes underwent a mean of 6.4 anti-VEGF injections, gaining a mean of +4.2 letters (95% confidence interval for mean gain: +4.0 to +4.5 letters, pConclusionIn clinical practice, patients with DMO undergo fewer anti-VEGF injections and exhibit worse visual gains compared with patients in randomised clinical trials. Visual outcomes correlate with treatment intensity at 1 year, with ceiling effects related to baseline VA.

Purpose This study assessed anti–vascular endothelial growth factor (VEGF) therapy intensity and its relationship with visual acuity (VA) change in real-world neovascular age-related macular degeneration (nAMD) patients. Design This retrospective analysis was performed on a large database of aggregated, longitudinal, de-identified electronic medical records from a geographically and demographically diverse sample of patients of United States retina specialists (Vestrum Health Retina Database). Participants Treatment-naive nAMD patients who underwent anti-VEGF injections between January 1, 2012, and October 31, 2016, were eligible if follow-up data were available before October 31, 2017. Methods Age, gender, anti-VEGF treatment type, number of treatments, and VA were extracted from the database. Main Outcome Measure Mean VA change assessed at 1 year and stratified based on number of anti-VEGF injections received over 1 year. Results In this analysis, 49 485 eyes were included. The mean age was 80.9 years, and 64% were female. Mean baseline VA was 53.8 letters (Snellen equivalent, 20/80). At 1 year, after a mean of 7.3 anti-VEGF injections, there was a mean gain of 1 letter (0.95 letter; 95% confidence interval [CI] for change in VA, +0.77 to +1.13 letter; P Conclusions Real-world nAMD patients receive fewer anti-VEGF injections and experience worse visual outcomes compared with patients receiving fixed, frequent therapy in randomized controlled trials. Mean change in VA correlates with treatment intensity at 1 year, but with ceiling effects related to treatment intensity and baseline VA. Older patients and those with poor baseline VA may be particularly prone to undertreatment.

This essay analyzes the scientific evidence that forms the basis of bioactive materials, covering the fundamental understanding of bioactivity phenomena and correlation with the mechanisms of biocompatibility of biomaterials. This is a detailed assessment of performance in areas such as bone-induction, cell adhesion, immunomodulation, thrombogenicity and antimicrobial behavior. Bioactivity is the modulation of biological activity by characteristics of the interfacial region that incorporates the material surface and the immediate local host tissue. Although the term ‘bioactive material’ is widely used and has a well understood general meaning, it would be useful now to concentrate on this interfacial region, considered as ‘the bioactivity zone’. Bioactivity phenomena are either due to topographical/micromechanical characteristics, or to biologically active species that are presented in the bioactivity zone. Examples of topographical/micromechanical effects are the modulation of the osteoblast – osteoclast balance, nanotopographical regulation of cell adhesion, and bactericidal nanostructures. Regulation of bioactivity by biologically active species include their influence, especially of metal ions, on signaling pathways in bone formation, the role of cell adhesion molecules and bioactive peptides in cell attachment, macrophage polarization by immunoregulatory molecules and antimicrobial peptides. While much experimental data exists to demonstrate the potential of such phenomena, there are considerable barriers to their effective clinical translation. This essay shows that there is solid scientific evidence of the existence of bioactivity mechanisms that are associated with some types of biomaterials, especially when the material is modified in a manner designed to specifically induce that activity.

Aims Cardiac surgery in middle-income countries differs significantly from that in high-income countries regarding prevailing heart valve pathologies and access to cardiac surgery. Typically, rheumatic aortic regurgitation in the absence of calcification by far outweighs stenosis. As such, entirely different transcatheter aortic valve implantation (TAVI) concepts are required for these regions. The aim of the study was to evaluate the five-month performance of the SAT (Strait Access Technologies, Cape Town, South Africa) pericardial TAVI system in the orthotopic aortic position of juvenile sheep. Methods and results A self-homing, non-occlusive balloon-expandable TAVI system comprising a hollow balloon, stabilising locator trunks, a scalloped CoCr stent with elevating anchorage arms and decellularised, sandwich-crosslinked pericardium was compared with control surgical valves (Edwards PERIMOUNT) in sheep. The implantation period was five months. The tactile placement of the TAVI valves was accomplished without the need for rapid pacing. At termination, no structural degeneration was observed in either group. The TAVIs were well healed with the stent struts largely embedded in tissue. Correlating with sheep growth (weight gain of 40.4±13.0%) during the implantation period, mean transvalvular gradients increased from 3.08±1.95 mmHg to 8.50±5.38 mmHg (p=0.044) after five months. Conclusions A single-stage, balloon-expandable, easy to place TAVI system with antigen-depleted and antigen-masked bioprosthetic leaflets promises to address the distinct needs of low- and middle-income countries with regard to TAVI better than conventional systems.

Purpose To determine predictive factors of proliferative vitreoretinopathy (PVR) formation after uncomplicated primary retinal detachment repair. Methods Retrospective, single-center, case-control study of 74 consecutive patients with (37 eyes) and without (37 eyes) PVR formation after undergoing uncomplicated primary surgery for retinal detachment repair. Logistic regression was used to assess factors associated with PVR formation. Results Retinal detachment involving the macula was 4.2 times (adjusted odds ratio; 95% confidence interval, 1.4-12.9; P = 0.0119) more likely to have PVR formation compared with those without. Patients who were current or former smokers were 3.6 times (adjusted odds ratio; 95% confidence interval, 1.1-11.7; P = 0.0352) more likely to have PVR formation compared with nonsmokers. Compared with 25-gauge (g) vitrectomy, larger gauge vitrectomy (20 g or 23 g) was 3.6 times (adjusted odds ratio; 95% confidence interval, 1.2-11.3; P = 0.0276) more likely to have PVR formation. Duration of retinal detachment symptoms, high myopia, lens status, lattice degeneration, location of retinal break, number of retinal breaks, and surgical technique (e.g., scleral buckle with or without vitrectomy versus vitrectomy alone) were not found to be predictive of PVR formation. Conclusion Cigarette smoking and macular involvement are significant risk factors predictive of PVR formation after uncomplicated primary retinal detachment repair.

Biomaterials have gained much interest as a very important category of materials because of their wide application in medicine and benefit to patient such as increased longevity and improved quality of life. The biocompatibility of biomaterials is an important issue, and many researches have been devoted during the past decades in this field. In this review, we will focus on basic concepts and key terminologies in the fields of biomaterials and biocompatibility. Moreover, the most recent definitions of the terms related to biomaterials and biocompatibility provided in the 2018 Chengdu consensus conference are stated. Some standard methods for evaluating the concepts related to biomaterials and biocompatibility are also listed in this article.

A consensus conference on the language of biomaterials science held back in 1986 identified a series of definitions that underpinned this important area. Language naturally evolves and, over 30 years later, it was deemed relevant to re-visit this topic. Within a critical, fast-moving field such as medical technology, it is essential that this evolution identifies with accuracy, validity, and clarity while avoiding the dangers of hype, exaggeration, and advocacy. This Perspectives Paper summarizes the major conclusions of a new consensus conference held in Chengdu, China, in June 2018 that debated the words currently used in biomaterials science. The occasion was used to re-evaluate some conventional terms that needed updating in the light of scientific and clinical advances, and also to assess and develop the terminology of growth areas such as tissue regeneration and biomaterials-related biotechnology. Among these forward-looking terms were tissue-inducing biomaterials, regeneration and its derivatives regenerative medicine and regenerative engineering, and several terms associated with microphysiological systems, organoid technology, and biomaterialomics. A full transcript of the conference will be published shortly. In June 2018, a Consensus Conference on Definitions in Biomaterials Science took place in Chengdu, China. The present paper discusses the rationale for this conference and summarizes the main definitions that were agreed. These especially concerned some of the terms recently introduced in the areas of regenerative medicine and regenerative engineering

This study assessed real-world visual acuity (VA) outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME).This retrospective analysis was performed on a large database of aggregated, longitudinal electronic medical records from a geographically and demographically diverse sample of patients of United States retina specialists (Vestrum Health Retina Database).DME patient eyes that underwent ≥3 monthly anti-VEGF injections within 4 months of the first injection and between January 2011 and March 2017 were eligible if follow-up data were available prior to March 2018.The eyes were divided into 3 groups based on choice of initial intravitreal anti-VEGF agent (aflibercept, bevacizumab, or ranibizumab). These eyes were then subdivided into 3 cohorts, depending on length of follow-up (6, 12, or 24 months), with each cohort being mutually exclusive.VA outcomes and number of treatments were assessed on each cohort and stratified by baseline VA.A total of 15,608 DME patient eyes were included in this analysis. In the 12-month cohort, of 1379 eyes initially treated with aflibercept, the mean 12-month improvement was +5.5 letters (95% confidence interval [CI] +4.5 to +6.6 letters, P0.001) after 7.5 injections on average, with similar outcomes for bevacizumab (3109 eyes, +5.5 letters, 95% CI +4.7 to +6.3 letters, P0.001, average 7.9 injections), and for ranibizumab (1352 eyes, +4.0 letters, 95% CI +2.9 to +5.2 letters, P0.001, average 7.7 injections). The mean numbers of corticosteroid, macular, and panretinal laser treatment sessions were similar in each group. In the 12-month cohort, when stratified by baseline VA of 20/201 or worse, 20/71 to 20/200, 20/41 to 20/70, and 20/40 or better, the final mean letters gained or lost were +28.0, +10.2, +2.8, and -2.5 in the aflibercept group, +36.0, +7.8, +2.9, and -2.0 letters in the bevacizumab group, and +30.5, +7.9, +1.6, and -2.7 letters in the ranibizumab group, respectively.Real-world VA outcomes following anti-VEGF therapy for DME were meaningfully inferior to those noted in randomized, controlled trials. Eyes with better baseline VA experienced fewer letters gained compared with those with worse baseline VA. The initial choice of anti-VEGF agent did not correlate with visual outcomes.

Purpose We describe the presentation of patients developing endophthalmitis after intravitreal injection with vascular endothelial growth factor (VEGF) inhibitors. Moreover, we evaluate the management by comparing the outcomes of immediate tap and injection of intravitreal antibiotics (TAI) versus initial surgical pars plana vitrectomy (PPV). Finally, we analyze the predictive factors of visual outcomes at 6-month follow-up. Design Retrospective, single-center, nonrandomized interventional study. Participants Patients developing endophthalmitis after receiving an intravitreal injection of anti-VEGF agent between 2006 and 2016. Methods All patients received a vitreous biopsy sent for cultures before the initiation of treatment: TAI group versus PPV with intravitreal antibiotics (PPV group). Main Outcome Measures Best-corrected visual acuity (BCVA) at 6-month follow-up after treatment for endophthalmitis. Results A total of 258 357 intravitreal injections occurred over the course of the 10-year period, of which 40 patients (0.016%) had endophthalmitis within 3 weeks after injection. In total, 34 patients (85.0%) had pain and 25 patients (62.5%) had hypopyon on initial examination. Among 24 culture-positive cases, 66.7% of the causative organisms were coagulase-negative Staphylococcus , followed by Streptococcus species (10.0%). The best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution [logMAR]) at 6-month follow-up was significantly worse for patients who had a positive culture for Streptococcus species (4.0; standard deviation [SD], 0.8) (approximately light perception) compared with those who had a positive culture for coagulase-negative Staphylococcus (0.4; SD, 0.3) (∼20/50) ( P P = 0.03). There was no statistically significant difference in BCVA at 6-month follow-up between the TAI and PPV groups. Younger age ( Conclusions No significant difference in BCVA at 6-month follow-up was detected between the TAI and PPV groups. Younger age and lower IOP at presentation were associated with better visual outcomes at 6-month follow-up.

Real-world visual outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) have been reported in cohorts outside of the United States. This study sought to assess the relationship between presenting visual acuity (VA) and visual outcomes, as well as the potential impact of loss to follow-up, in real-world anti-VEGF-treated nAMD patients from the United States.Retrospective study of aggregated, longitudinal electronic medical records obtained from a geographically diverse sample of US retina specialists and included in the Vestrum Health Retina Database.Inclusion criteria were a diagnosis of nAMD, no previous treatment, and ≥3 monthly anti-VEGF injections in the first 4 months from diagnosis in patients diagnosed between January 2011 and July 2013.To model loss to follow-up, mutually exclusive cohorts of nAMD patients with loss to follow-up after specific time points of 6 and 12 months (i.e., no follow-up beyond) were compared with a separate cohort of patients who completed 24 months of follow-up ending prior to July 2015 (n = 2213).VA outcomes were assessed on each cohort as a whole, with additional stratification by baseline VA.The 6-, 12-, and 24-month cohorts received means of 5.4, 7.3, and 12.1 injections and showed no change, no change, and a mean change of +3.1 letters from baseline (95% confidence interval 1.8-4.4 letters, P0.01), respectively. When stratified by baseline VA, nearly all groups lose VA at their respective follow-up periods, except for those with baseline VA of 20/200 or worse.Real-world nAMD patients in the United States receive fewer anti-VEGF injections and experience worse visual outcomes compared with patients in randomized clinical trials, consistent with non-US studies. Patients with better VA at presentation tend to be particularly vulnerable to vision loss. Compared with other patients, those ultimately lost to follow-up have worse visual outcomes at, or prior to, their final visit, suggesting that loss to follow-up may lead to overestimation of visual outcomes in clinical studies of nAMD.

Bioinks are the basic building blocks for the fabrication of 3D bioprinted constructs. These bioinks play key roles in structural support, adhesion, and differentiation of incorporated cells. Due to diversity of tissue types found in the body, and the need to recapitulate many of the structural and functional characteristics of a target tissue, there are many potential bioinks, but relatively few at the moment possess optimal properties. Bioinks may be classified on the basis on their ultimate role in a 3D bioprinted construct such as imparting biological functionality, serving as sacrificial material, or supporting and providing rigidity to complex constructs. Physical, mechanical and biological characteristics must all be taken into account in the design and composition of bioinks. The incorporation of guidance cues such as topography, growth factors, and morphogens is necessary to control cell fate. These 3D bioprinted constructs should be integrated into bioreactor systems, to support tissue development. Finally, the methodologies to non-destructively monitor both deposited bioinks and construct maturation are necessary for the successful development of a functional tissue.

This work combines large area ToF-SIMS imaging with multivariate analysis methods in order to characterise a cold-atmospheric plasma treatment of the surface of an automotive grade polypropylene. Data pre-processing steps are also presented alongside their main challenges. The results enabled the investigation of the spatial distribution of the treatment for different standoff distances as well as the effects of plasma plume mixing with atmosphere.

Procedures for the evaluation of tissue-engineering processes, including those used for the testing of the relevant biomaterials, have not been developed in a logical manner. This perspectives paper discusses the limitations of testing regimes and recommends a very different approach. The main emphasis is on the existing methods for assessing the biological safety of these biomaterials, which, it is suggested, are irrelevant for evaluating materials that are intended to facilitate the generation of new tissue. An algorithm is proposed that sets out the pathway from materials design and characterization through to the production of a file that sets out full biocompatibility, functionality, and tissue incorporation data that are suitable for regulatory consideration for first-in-man experiences. Central to this algorithm is the choice of animal models and the real-time monitoring of the implanted construct performance.

Biocompatibility is a very common word that is used within biomaterial science and used for description of the interactions between the foreign material and the body. However, the meaning of biocompatibility as well as the mechanisms that collectively constitutes is still unclear. With the advance of nanotechnology, new concerns have been observed related to biocompatibility of these biomaterials. Due to their small size and variability of their physical and chemical properties, nanoparticles’ (NP) distribution within the body and interactions with the target cells and tissues are highly variable. Here, we tried to provide an overview about NPs, the concept of biocompatibility and biocompatibility-related issues in nanomedicine and several different NPs.

This study assessed anti-vascular endothelial growth factor (VEGF) therapy intensity and its relationship with visual acuity (VA) change in real-world neovascular age-related macular degeneration (nAMD) patients.This retrospective analysis was performed on a large database of aggregated, longitudinal, de-identified electronic medical records from a geographically and demographically diverse sample of patients of United States retina specialists (Vestrum Health Retina Database).Treatment-naïve nAMD patients who underwent anti-VEGF injections between January 1, 2012, and October 31, 2016, were eligible if follow-up data were available before October 31, 2017.Age, gender, anti-VEGF treatment type, number of treatments, and VA were extracted from the database.Mean VA change assessed at 1 year and stratified based on number of anti-VEGF injections received over 1 year.In this analysis, 49 485 eyes were included. The mean age was 80.9 years, and 64% were female. Mean baseline VA was 53.8 letters (Snellen equivalent, 20/80). At 1 year, after a mean of 7.3 anti-VEGF injections, there was a mean gain of 1 letter (0.95 letter; 95% confidence interval [CI] for change in VA, +0.77 to +1.13 letter; P0.001). When stratified by anti-VEGF agent, the mean VA changes were nearly identical at 1 year. There was a linear relationship between mean letters gained and mean number of injections, between 4 and 10 injections over 1 year, with 4 or fewer or 10 or more injections associated with loss of vision or a plateau, respectively. Greater mean 1-year change in VA also trended with worse baseline VA; those patients with better VA at presentation tended to be particularly vulnerable to vision loss. Those who received the fewest injections tended to be older and have worse baseline VA.Real-world nAMD patients receive fewer anti-VEGF injections and experience worse visual outcomes compared with patients receiving fixed, frequent therapy in randomized controlled trials. Mean change in VA correlates with treatment intensity at 1 year, but with ceiling effects related to treatment intensity and baseline VA. Older patients and those with poor baseline VA may be particularly prone to undertreatment.

Endovascular treatment of thoracic aortic pathologies has recently progressed towards more proximal pathologies, including those of the aortic arch and ascending aorta where there is a higher risk for stent-graft migration during the deployment or the moulding procedure due to the beating and ejecting heart. Typical measures to prevent dislodgement of the balloon or the stent-graft during the procedure are rapid pacing or pharmacologically induced hypotension. We present a circular and fully non-occlusive stent-graft moulding balloon that does not require any reduction of cardiac output or hypotension during inflation, moulding and deflation of the balloon.

This paper addresses a significant paradox in biomaterials science; biocompatibility phenomena have been experienced and described for over 50 years but without an agreed understanding of the framework of mechanisms that control the events that occur when a biomaterial is exposed to the tissues of the human body. The need for such an understanding has become more urgent as biomaterials are now used in wide-ranging applications such as tissue engineering, drug and gene delivery, and imaging contrast agents. A detailed analysis of these phenomena, especially in terms of clinical outcomes rather than in vitro experiments, determines that two overarching mechanisms, mechanotransduction and sterile inflammation associated with damage-associated molecular patterns, are responsible for the vast majority of phenomena. In contrast, interfacial interactions, for so long being assumed to play pivotal roles in biocompatibility, especially relating to protein adsorption, are actually relatively unimportant unless, through conformational changes, they are able to participate in 3D ECM development. Critical to this new view of biocompatibility is the fact that the combination of mechanotransduction and sterile inflammation, especially focusing on inflammasome activation and the immunology of the balance between inflammation and fibrosis, allows biomaterials science to encompass mechanisms of innate and adaptive immunity without recourse to the traditional implications of pathogen induced responses of the immune system. In this way, a system of biocompatibility pathways can be generated; these are able to explain a wide range of clinical biocompatibility challenges, including nanoparticle translocation and internalization, intraocular lens opacification, leukocyte-dominated responses to metallic wear debris in joint replacement, stem cell differentiation of nanostructured hydrogels, tissue responses to incontinence meshes, and restenosis of intravascular stents. Perhaps even more importantly, the identification of these molecular pathways of biocompatibility offers prospects of the control of the host response by targeting specific points in these pathways, for example the inhibition of epithelial to mesenchymal transformation that can result in excessive fibrosis, and the inhibition of activation of the NLRP3 inflammasome following exposure to biomaterial-induced stresses; this should lead to a more effective translation of biocompatibility understanding into better clinical outcomes.

The rising incidence of bone disorders has resulted in the need for more effective therapies to meet this demand, exacerbated by an increasing ageing population. Bone tissue engineering is seen as a means of developing alternatives to conventional bone grafts for repairing or reconstructing bone defects by combining biomaterials, cells and signalling factors. However, skeletal tissue engineering has not yet achieved full translation into clinical practice as a consequence of several challenges. The use of additive manufacturing techniques for bone biofabrication is seen as a potential solution, with its inherent capability for reproducibility, accuracy and customisation of scaffolds as well as cell and signalling factor delivery. This review highlights the current research in bone biofabrication, the necessary factors for successful bone biofabrication, in addition to the current limitations affecting biofabrication, some of which are a consequence of the limitations of the additive manufacturing technology itself.

Over the past ten years, tissue engineering has witnessed significant technological and scientific advancements. Progress in both stem cell science and additive manufacturing have established new horizons in research and are poised to bring improvements in healthcare closer to reality. However, more sophisticated indications such as the scale-up fabrication of biological structures (e.g., human tissues and organs) still require standardization. To that end, biocompatible electronics may be helpful in the biofabrication process. Here, we report the results of our systematic exploration to seek biocompatible/degradable functional electronic materials that could be used for electronic device fabrications. We investigated the electronic properties of various biomaterials in terms of energy diagrams, and the energy band gaps of such materials were obtained using optical absorption spectroscopy. The main component of an electronic device is manufactured with semiconductor materials (i.e., Eg between 1 to 2.5 eV). Most biomaterials showed an optical absorption edge greater than 2.5 eV. For example, fibrinogen, glycerol, and gelatin showed values of 3.54, 3.02, and 3.0 eV, respectively. Meanwhile, a few materials used in the tissue engineering field were found to be semiconductors, such as the phenol red in cell culture media (1.96 eV energy band gap). The data from this research may be used to fabricate biocompatible/degradable electronic devices for medical applications.

More than 6 billion people live outside industrialized countries and have insufficient access to cardiac surgery. Given the recently confirmed high prevailing mortality for rheumatic heart disease in many of these countries together with increasing numbers of patients needing interventions for lifestyle diseases due to an accelerating epidemiological transition, a significant need for cardiac surgery could be assumed. Yet, need estimates were largely based on extrapolated screening studies while true service levels remained unknown. A multi-author effort representing 16 high-, middle-, and low-income countries was undertaken to narrow the need assessment for cardiac surgery including rheumatic and lifestyle cardiac diseases as well as congenital heart disease on the basis of existing data deduction. Actual levels of cardiac surgery were determined in each of these countries on the basis of questionnaires, national databases, or annual reports of national societies. Need estimates range from 200 operations per million in low-income countries that are nonendemic for rheumatic heart disease to >1,000 operations per million in high-income countries representing the end of the epidemiological transition. Actually provided levels of cardiac surgery range from 0.5 per million in the assessed low- and lower-middle income countries (average 107 ± 113 per million; representing a population of 1.6 billion) to 500 in the upper-middle-income countries (average 270 ± 163 per million representing a population of 1.9 billion). By combining need estimates with the assessment of de facto provided levels of cardiac surgery, it emerged that a significant degree of underdelivery of often lifesaving open heart surgery does not only prevail in low-income countries but is also disturbingly high in middle-income countries.

Imperial porphyry was greatly admired during the Roman and Byzantine periods because the deep purple of the stone was closely associated with the chosen colour of the Emperor. Outcrops of this hard volcanic rock are extremely restricted and only found in a small area of the eastern Egyptian desert. The quarries were kept under close Imperial control, with the vast majority of the items produced only intended for Imperial use or patronage: sculpture, columns, baths, basins and sarcophagi. The numbers of imported coloured marbles in Roman Britain are not great and are generally restricted to small individual pieces, many of which show signs of having been cut to shape, suggesting they were employed essentially as a luxury item for decorative purposes in selected buildings of Roman Britain, or perhaps as pietra dura in furniture. Amongst these imported coloured marbles are a small number of pieces of Imperial porphyry, associated with a limited number of sites.

This article introduces biomedical and dental materials that were used in medicine and dentistry technology. Comprehensive discussion was carried out within three scopes of Clinical Applications; Evolution of Biomaterials; and Current and Future Trends of Biomedical Materials. Compromised quality of human tissue or organ due to disease, malfunction and structural degeneration lead to the creation of new technologies to replace or augment the affected parts. These new technologies are reviewed in the topic of Clinical Applications. To support the creation of the new technologies, special biomaterials with specific materials properties are required. This issue was explained in the second topic of this article and discussed within five sub categories of the Metals, Ceramics, Polymers, Natural Materials, and Biomaterials Surfaces. In the final part of this article major changes in both medical practice and materials technology were presented in the perspective of the current and future trends.

The effects of flame treatment on the surface characteristics of four injection moulded, automotive grade, polypropylene samples, pigmented with carbon black, have been studied. The changes in wettability have been monitored by water contact angle and Dyne inks, whilst XPS has been used to establish the changes in oxygen surface concentration as a function of flame treatment. As expected carbon pigmented and carbon plus talc filled samples showed a significant increase in oxygen concentration and surface wettability with increasing flame treatment. For the glass filled sample this effect was not so pronounced. Inspection of the XPS valence band shows initial attack in the flame treatment process to be at the pendant methyl group of the poly(propylene) molecular architecture. XPS in conjunction with cluster ion bombardment shows the depth of surface treatment to range from ca. 7 nm at one pass of flame treatment to some 15 nm following seven passes. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) shows the segregation of characteristic additives during the injection moulding process which are subsequently greatly reduced during the flame treatment. As treatment level increases oxygen increases from mono-atomic to diatomic attachment. This work extends the understanding of the flame treatment of moulded polyolefines and establishes that the beneficial properties conferred are the result of the conjoint effect of the oxygenation of the bulk polymer along with the removal of surface segregated processing aids.

Efficient function and long-term durability without the need for anticoagulation, coupled with the ability to be accommodated in many different types of patient, are the principal requirements of replacement heart valves. Although the clinical use of valves appeared to have remained steady for several decades, the evolving demands for the elderly and frail patients typically encountered in the developed world, and the needs of much younger and poorer rheumatic heart disease patients in the developing world have now necessitated new paradigms for heart valve technologies and associated materials. This includes further consideration of durable elastomeric materials. The use of polymers to produce flexible leaflet valves that have the benefits of current commercial bioprosthetic and mechanical valves without any of their deficiencies has been held desirable since the mid 1950s. Much attention has been focused on thermoplastic polyurethanes in view of their generally good physico-chemical properties and versatility in processing, coupled with the improving biocompatibility and stability of recent formulations. Accelerated in vitro durability of between 600 and 1000 million cycles has been achieved using polycarbonate urethanes, and good resistance to degradation, calcification and thrombosis in vivo has been shown with some polysiloxane-based polyurethanes. Nevertheless, polymeric valves have remained relegated to use in temporary ventricular assist devices for bridging heart failure patients to transplantation. Some recent studies suggest that there is a greater degree of instability in thermoplastic materials than hitherto believed so that significant challenges remain in the search for the combination of durability and biocompatibility that would allow polymeric valves to become a clinical reality for surgical implantation. Perhaps more importantly, they could become candidates for use in situations where minimally invasive transcatheter procedures are used to replace diseased valves. Being amenable to relatively inexpensive mass production techniques, the attainment of this goal could benefit very large numbers of patients in developing and emerging countries who currently have no access to treatment for rheumatic heart disease that is so prevalent in these areas. This review discusses the evolution and current status of polymeric valves in wide-ranging circumstances.

We describe the presentation of patients developing endophthalmitis after intravitreal injection with vascular endothelial growth factor (VEGF) inhibitors. Moreover, we evaluate the management by comparing the outcomes of immediate tap and injection of intravitreal antibiotics (TAI) versus initial surgical pars plana vitrectomy (PPV). Finally, we analyze the predictive factors of visual outcomes at 6-month follow-up.Retrospective, single-center, nonrandomized interventional study.Patients developing endophthalmitis after receiving an intravitreal injection of anti-VEGF agent between 2006 and 2016.All patients received a vitreous biopsy sent for cultures before the initiation of treatment: TAI group versus PPV with intravitreal antibiotics (PPV group).Best-corrected visual acuity (BCVA) at 6-month follow-up after treatment for endophthalmitis.A total of 258 357 intravitreal injections occurred over the course of the 10-year period, of which 40 patients (0.016%) had endophthalmitis within 3 weeks after injection. In total, 34 patients (85.0%) had pain and 25 patients (62.5%) had hypopyon on initial examination. Among 24 culture-positive cases, 66.7% of the causative organisms were coagulase-negative Staphylococcus, followed by Streptococcus species (10.0%). The best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution [logMAR]) at 6-month follow-up was significantly worse for patients who had a positive culture for Streptococcus species (4.0; standard deviation [SD], 0.8) (approximately light perception) compared with those who had a positive culture for coagulase-negative Staphylococcus (0.4; SD, 0.3) (∼20/50) (P0.0001). Compared with the TAI group, a higher proportion of samples were culture-positive in the PPV group (90.9% vs. 48.3%, P = 0.03). There was no statistically significant difference in BCVA at 6-month follow-up between the TAI and PPV groups. Younger age (85 years) and lower intraocular pressure (IOP) (≤25 mmHg) at presentation were predictive of achieving a BCVA of 20/400 or better at 6-month follow-up after treatment. Initial management (TAI vs. PPV), duration of symptoms, presence of pain, presence of hypopyon, presenting BCVA, and culture status (positive vs. negative) were not found to be predictive of visual outcomes at 6-month follow-up.No significant difference in BCVA at 6-month follow-up was detected between the TAI and PPV groups. Younger age and lower IOP at presentation were associated with better visual outcomes at 6-month follow-up.

Geographic atrophy is an advanced form of age-related macular degeneration (AMD) and a leading cause of vision loss for which there are no approved treatments. Genetic studies in AMD patients have implicated dysregulation of the alternative complement pathway in the pathogenesis of geographic atrophy. Lampalizumab is a potential therapeutic that targets complement factor D, a pivotal activator of the alternative complement pathway. The MAHALO phase 2 clinical trial was a multicenter, randomized, controlled study that evaluated lampalizumab administered by intravitreal injection monthly (n = 42) and every other month (n = 41) versus sham control (n = 40) in patients with geographic atrophy secondary to AMD. The primary endpoint was the mean change in lesion area from baseline to month 18 as measured by fundus autofluorescence. Specific AMD-associated genetic polymorphisms were also analyzed. The MAHALO study met its primary efficacy endpoint with an acceptable safety profile; monthly lampalizumab treatment demonstrated a 20% reduction in lesion area progression versus sham control [80% confidence interval (CI), 4 to 37%]. A more substantial monthly treatment benefit of 44% reduction in geographic atrophy area progression versus sham control (95% CI, 15 to 73%) was observed in a subgroup of complement factor I (CFI) risk-allele carriers (57% of the patients analyzed were CFI risk-allele carriers). The MAHALO study shows a potential treatment effect in patients with geographic atrophy and supports therapeutic targeting of the alternative complement pathway for treating AMD pathogenesis.

The medical-technology sector must educate society in an unbiased rational way about the successes and benefits of biotechnology innovation.

The pathogenesis of kidney disease and injury is complex, as are the multiple functions that the kidney performs and the microenvironment characteristics within the organ. It should not be surprising that engineering solutions to the treatment of these conditions have been extremely difficult to develop, unlike the situation in the heart, where multiple technologies play significant roles in reducing mortality and morbidity. Transplantation is by far the best solution for end-stage renal failure, giving much better outcomes than chronic hemodialysis. The bioartificial kidney has been very difficult to develop to the point where it can be clinically and commercially successful, while attempts at kidney tissue engineering are still in their infancy. This chapter reviews the engineering challenges that are faced in the search for alternative therapies, which are much needed in the light of continuing donor organ shortages, and attempts to bring a systems engineering approach to these problems.

This chapter deals with the role of the immune response in the biocompatibility of biomaterials used in renal technologies, the nature of which is profoundly influenced by the already compromised immune system found in uremic patients. In biomaterials science in general, there has been much confusion over the role that the immune response plays in biocompatibility phenomena. To a large extent this has been associated with lack of any particular need to equate the usual sequence of inflammation and repair that accompanies the introduction of biomaterials into a host site with the innate immune response, even though the main cellular and humoral features of the latter were usually evident in the former. At the same time, adaptive immune responses were not considered particularly relevant to the biocompatibility of biomaterials since they do not normally contain antigens that initiate this type of response. As described in this chapter, the overall understanding of biocompatibility is now changing, with a more informed incorporation of toxicological and immunological mechanisms into the host response to biomaterials. This has been partly associated with the different modalities of biomaterials use in therapies, especially with more biologically active materials used as scaffolds in tissue engineering and the type of prolonged extracorporeal contact that is seen with hemodialysis.