Abstract The manner in which a mutually acceptable co-existence of biomaterials and tissues is developed and sustained has been the focus of attention in biomaterials science for many years, and ...forms the foundation of the subject of biocompatibility. There are many ways in which materials and tissues can be brought into contact such that this co-existence may be compromised, and the search for biomaterials that are able to provide for the best performance in devices has been based upon the understanding of all the interactions within biocompatibility phenomena. Our understanding of the mechanisms of biocompatibility has been restricted whilst the focus of attention has been long-term implantable devices. In this paper, over 50 years of experience with such devices is analysed and it is shown that, in the vast majority of circumstances, the sole requirement for biocompatibility in a medical device intended for long-term contact with the tissues of the human body is that the material shall do no harm to those tissues, achieved through chemical and biological inertness. Rarely has an attempt to introduce biological activity into a biomaterial been clinically successful in these applications. This essay then turns its attention to the use of biomaterials in tissue engineering, sophisticated cell, drug and gene delivery systems and applications in biotechnology, and shows that here the need for specific and direct interactions between biomaterials and tissue components has become necessary, and with this a new paradigm for biocompatibility has emerged. It is believed that once the need for this change is recognised, so our understanding of the mechanisms of biocompatibility will markedly improve.
The field of tissue engineering has tantalizingly offered the possibility of regenerating new tissue in order to treat a multitude of diseases and conditions within the human body. Nevertheless, in ...spite of significant progress with
and small animal studies, progress toward realizing the clinical and commercial endpoints has been slow and many would argue that ultimate goals, especially in treating those conditions which, as yet, do not have acceptable conventional therapies, may never be reached because of flawed scientific rationale. In other words, sustainable tissue engineering may not be achievable with current approaches. One of the major factors here is the choice of biomaterial that is intended, through its use as a "scaffold," to guide the regeneration process. For many years, effective specifications for these biomaterials have not been well-articulated, and the requirements for biodegradability and prior FDA approval for use in medical devices, have dominated material selection processes. This essay argues that these considerations are not only wrong in principle but counter-productive in practice. Materials, such as many synthetic bioabsorbable polymers, which are designed to have no biological activity that could stimulate target cells to express new and appropriate tissue, will not be effective. It is argued here that a traditional 'scaffold' represents the wrong approach, and that tissue-engineering templates that are designed to replicate the niche, or microenvironment, of these target cells are much more likely to succeed.
Abstract The situations in which biomaterials are currently used are vastly different to those of just a decade ago. Although implantable medical devices are still immensely important, medical ...technologies now encompass a range of drug and gene delivery systems, tissue engineering and cell therapies, organ printing and cell patterning, nanotechnology based imaging and diagnostic systems and microelectronic devices. These technologies still encompass metals, ceramics and synthetic polymers, but also biopolymers, self assembled systems, nanoparticles, carbon nanotubes and quantum dots. These changes imply that our original concepts of biomaterials and our expectations of their performance also have to change. This Leading Opinion Paper addresses these issues. It concludes that many substances which hitherto we may not have thought of as biomaterials should now be considered as such so that, alongside the traditional structural biomaterials, we have substances that have been engineered to perform functions within health care where their performance is directly controlled by interactions with tissues and tissue components. These include engineered tissues, cells, organs and even viruses. This essay develops the arguments for a radically different definition of a biomaterial.
Psychological tests typically include a response scale whose purpose it is to organize and constrain the options available to respondents and facilitate scoring. One such response scale is the Likert ...scale, which initially was introduced to have a specific 5-point form. In practice, such scales have varied considerably in the nature and number of response options. However, relatively little consensus exists regarding several questions that have emerged regarding the use of Likert-type items. First, is there a "psychometrically optimal" number of response options? Second, is it better to include an even or odd number of response options? Finally, do visual analog items offer any advantages over Likert-type items? We studied these questions in a sample of 1,358 undergraduates who were randomly assigned to groups to complete a common personality measure using response scales ranging from 2 to 11 options, and a visual analog condition. Results revealed attenuated psychometric precision for response scales with 2 to 5 response options; interestingly, however, the criterion validity results did not follow this pattern. Also, no psychometric advantages were revealed for any response scales beyond 6 options, including visual analogs. These results have important implications for psychological scale development.
Public Significance Statement
We studied several aspects of questionnaire response scales and their impact on the reliability and validity of a personality measure. We found that smaller numbers of response options have a negative impact on the measurement precision of a scale, which has important implications how psychological measures should be developed and used in practice.
Sparse seismic instrumentation in the oceans limits our understanding of deep Earth dynamics and submarine earthquakes. Distributed acoustic sensing (DAS), an emerging technology that converts ...optical fiber to seismic sensors, allows us to leverage pre-existing submarine telecommunication cables for seismic monitoring. Here we report observations of microseism, local surface gravity waves, and a teleseismic earthquake along a 4192-sensor ocean-bottom DAS array offshore Belgium. We observe in-situ how opposing groups of ocean surface gravity waves generate double-frequency seismic Scholte waves, as described by the Longuet-Higgins theory of microseism generation. We also extract P- and S-wave phases from the 2018-08-19 Formula: see text Fiji deep earthquake in the 0.01-1 Hz frequency band, though waveform fidelity is low at high frequencies. These results suggest significant potential of DAS in next-generation submarine seismic networks.
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.
To assess visual acuity (VA) outcomes and antivascular endothelial growth factor (anti-VEGF) treatment intensity in diabetic macular oedema (DMO).
Retrospective 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).
At 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, p<0.001). When stratified by anti-VEGF medication and by years 2013-2018, no clinically meaningful differences in injection frequency or 1-year VA change resulted. At 1 year, 50% of eyes received ≤6 injections, while <20% received 10-13 injections, representing monthly treatment. Mean letters gained at 1 year generally showed a linear relationship with mean number of anti-VEGF injections, beyond two injections. Eyes with good baseline VA (≥20/40) generally were at risk of VA loss at 1 year; those with moderately severe baseline impairment (20/70 to 20/200) who received ≥10 injections improved by a mean of +10.3 letters.
In 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.
Photoinduced electron transfer (PET) is a phenomenon whereby the absorption of light by a chemical species provides an energetic driving force for an electron-transfer reaction
. This mechanism is ...relevant in many areas of chemistry, including the study of natural and artificial photosynthesis, photovoltaics and photosensitive materials. In recent years, research in the area of photoredox catalysis has enabled the use of PET for the catalytic generation of both neutral and charged organic free-radical species. These technologies have enabled previously inaccessible chemical transformations and have been widely used in both academic and industrial settings. Such reactions are often catalysed by visible-light-absorbing organic molecules or transition-metal complexes of ruthenium, iridium, chromium or copper
. Although various closed-shell organic molecules have been shown to behave as competent electron-transfer catalysts in photoredox reactions, there are only limited reports of PET reactions involving neutral organic radicals as excited-state donors or acceptors. This is unsurprising because the lifetimes of doublet excited states of neutral organic radicals are typically several orders of magnitude shorter than the singlet lifetimes of known transition-metal photoredox catalysts
. Here we document the discovery, characterization and reactivity of a neutral acridine radical with a maximum excited-state oxidation potential of -3.36 volts versus a saturated calomel electrode, which is similarly reducing to elemental lithium, making this radical one of the most potent chemical reductants reported
. Spectroscopic, computational and chemical studies indicate that the formation of a twisted intramolecular charge-transfer species enables the population of higher-energy doublet excited states, leading to the observed potent photoreducing behaviour. We demonstrate that this catalytically generated PET catalyst facilitates several chemical reactions that typically require alkali metal reductants and can be used in other organic transformations that require dissolving metal reductants.
Abstract 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.
PDF
