Achieving net-zero in the dry eye disease care pathway.

Climate change is a threat to human health and wellbeing across the world. In recent years, there has been a surge in awareness of this crisis, leading to many countries and organisations setting "net-zero" targets. This entails minimising carbon emissions and neutralising remaining emissions by removing carbon from the atmosphere.

Triggered metabolism of adenosine triphosphate as an explanation for the chemical heterogeneity of heterotopic ossification.

Heterotopic ossification (HO), the pathological formation of bone in soft tissues, is a debilitating condition, as well as one of the few instances of de novo bone formation in adults. Chemical mapping of HO tissue showed distinct islands of calcium phosphate within phosphate-deficient, calcium-rich regions, suggesting a transition to apatitic bone mineral from a non-phosphatic precursor. The transition of amorphous calcium carbonate (ACC), a generally suggested bone-mineral precursor, in physiological conditions was thus investigated.

Chemobrionic structures in tissue engineering: self-assembling calcium phosphate tubes as cellular scaffolds.

A diverse range of complex patterns and mineralised hierarchical microstructures can be derived from chemobrionic systems, with formation driven by complex reaction-diffusion mechanisms far from thermodynamic equilibrium. In these experiments, self-assembling calcium phosphate tubes are generated using hydrogels made with 1 M calcium solutions layered with solutions of dibasic sodium phosphate over a range of concentrations between 0.2-1 M.

Organotypic Culture of Bone-Like Structures Using Composite Ceramic-Fibrin Scaffolds.

We have developed an organotypic culture system that allows the production of bone tissue features on a centimeter scale. A composite, calcium phosphate-strained fibrin gel system is able to organize itself in the presence of osteoblastic cells, creating basic hierarchical units as seen in vivo, and can be modified to produce a range of other tissues that require such directional structuring. Constructs evolve over time into multi-compositional structures containing a high mineral content and terminally differentiated, osteocyte-like cells.

Sustained release of decorin to the surface of the eye enables scarless corneal regeneration.

Disorganization of the transparent collagenous matrix in the cornea, as a consequence of a variety of infections and inflammatory conditions, leads to corneal opacity and sight-loss. Such corneal opacities are a leading cause of blindness, according to the WHO. Public health programs target prevention of corneal scarring, but the only curative treatment of established scarring is through transplantation.

Formulation of a covalently bonded hydroxyapatite and poly(ether ether ketone) composite.

Spinal fusion devices can be fabricated from composites based on combining hydroxyapatite and poly(ether ether ketone) phases. These implants serve as load-bearing scaffolds for the formation of new bone tissue between adjacent vertebrae. In this work, we report a novel approach to covalently bond hydroxyapatite and poly(ether ether ketone) to produce a novel composite formulation with enhanced interfacial adhesion between phases.

Structuring of Hydrogels across Multiple Length Scales for Biomedical Applications.

The development of new materials for clinical use is limited by an onerous regulatory framework, which means that taking a completely new material into the clinic can make translation economically unfeasible. One way to get around this issue is to structure materials that are already approved by the regulator, such that they exhibit very distinct physical properties and can be used in a broader range of clinical applications. Here, the focus is on the structuring of soft materials at multiple length scales by modifying processing conditions.

Interfacial Mineral Fusion and Tubule Entanglement as a Means to Harden a Bone Augmentation Material.

A new bone augmenting material is reported, which is formed from calcium-loaded hydrogel-based spheres. On immersion of these spheres in a physiological medium, they become surrounded with a sheath of precipitate, which ruptures due to a build-up in osmotic pressure. This results in the formation of mineral tubes that protrude from the sphere surface.

Effects of freezing, fixation and dehydration on surface roughness properties of porcine left anterior descending coronary arteries.

Background: To allow measurements of surface roughness to be made of coronary arteries using various imaging techniques, chemical processing, such as fixation and dehydration, is commonly used. Standard protocols suggest storing fresh biological tissue at -40°C. The aim of this study was to quantify the changes caused by freezing and chemical processing to the surface roughness measurements of coronary arteries, and to determine whether correction factors are needed for surface roughness measurements of coronary arteries following chemical processes typically used before imaging these arteries.

Calcium pre-conditioning substitution enhances viability and glucose sensitivity of pancreatic beta-cells encapsulated using polyelectrolyte multilayer coating method.

Type I diabetics are dependent on daily insulin injections. A therapy capable of immunoisolating pancreatic beta-cells and providing normoglycaemia is an alternative since it would avoid the late complications associated with insulin use. Here, 3D-concave agarose micro-wells were used to culture robust pancreatic MIN-6 cell spheroids within 24 hours that were shown to exhibit cell-cell contact and uniform size (201 ± 2 μm).

Biologically Analogous Calcium Phosphate Tubes from a Chemical Garden.

Calcium phosphate (CaPO) tubes with features comparable to mineralized biological microstructures, such as Haversian canals, were grown from a calcium gel/phosphate solution chemical garden system. A significant difference in gel mass in response to high and low solute phosphate equivalent environments existed within 30 min of solution layering upon gel (p = 0.0067), suggesting that the nature of advective movement between gel and solution is dependent on the solution concentration.

Antimicrobial peptide coatings for hydroxyapatite: electrostatic and covalent attachment of antimicrobial peptides to surfaces.

The interface between implanted devices and their host tissue is complex and is often optimized for maximal integration and cell adhesion. However, this also gives a surface suitable for bacterial colonization. We have developed a novel method of modifying the surface at the material-tissue interface with an antimicrobial peptide (AMP) coating to allow cell attachment while inhibiting bacterial colonization.

Bedside, Benchtop, and Bioengineering: Physicochemical Imaging Techniques in Biomineralization.

The need to quantify physicochemical properties of mineralization spans many fields. Clinicians, mineralization researchers, and bone tissue bioengineers need to be able to measure the distribution, quantity, and the mechanical and chemical properties of mineralization within a wide variety of substrates from injured muscle to electrospun polymer scaffolds and everything in between. The techniques available to measure these properties are highly diverse in terms of their complexity and utility.

Modification of gellan gum with nanocrystalline hydroxyapatite facilitates cell expansion and spontaneous osteogenesis.

Nanocomposites composed of hydrogels and calcium phosphates are of great interest in the development of bone graft replacements since they may have a structural and compositional resemblance to bone. Culture beads formed from such materials could be used in stirred tank culture and thereby enable cell expansion in a sufficiently efficient manner to allow for the generation of enough large number of cells for large-scale bone reconstruction. Although combinations of materials such as alginate, collagens, and various calcium phosphates have been investigated as culture beads, these materials are unsuitable for application since they have been shown to rapidly degrade in physiological conditions and enable relatively little tailoring of mechanical properties.

The effects of cobalt-chromium-molybdenum wear debris in vitro on serum cytokine profiles and T cell repertoire.

Cobalt-chromium-molybdenum (CoCrMo) alloy-based metal-on-metal prostheses have been the implant of choice for total hip replacement in younger patients. However 6.2% of patients require revision of their CoCrMo total hip replacement (THR) implant within five years of surgery and their use was restricted in 2013.

Nanoscale crystallinity modulates cell proliferation on plasma sprayed surfaces.

Calcium phosphate coatings have been applied to the surface of metallic prostheses to mediate hard and soft tissue attachment for more than 40years. Most coatings are formed of high purity hydroxyapatite, and coating methods are often designed to produce highly crystalline surfaces. It is likely however, that coatings of lower crystallinity can facilitate more rapid tissue attachment since the surface will exhibit a higher specific surface area and will be considerably more reactive than a comparable highly crystalline surface.

Exploiting cell-mediated contraction and adhesion to structure tissues in vitro.

Progress in tissue engineering is now impacting beyond the field of regenerative medicine. Engineered tissues are now used as tools to evaluate the toxicity of compounds or even to enable the modelling of disease. While many of the materials that are used to facilitate tissue growth are designed to enable cell attachment, many researchers consider that the contraction and modification of these matrices by attached cells is not desirable and take measures to prevent this from occurring.

Quantification of volume and size distribution of internalised calcium phosphate particles and their influence on cell fate.

We report preliminary findings suggesting that the diameter of the internalised calcium phosphate particles is critical to cell fate with particles/aggregates of particles of larger than 1.5 μm not processed by lysosomes leading to cell death. This has significant implications for the design of medical materials even from those consisting of non-toxic calcium phosphate salts.

Thiol modification of silicon-substituted hydroxyapatite nanocrystals facilitates fluorescent labelling and visualisation of cellular internalisation.

Calcium phosphates are used widely as orthopaedic implants and in nanocrystalline form to enable the transfer of genetic material into cells. Despite widespread use, little is known about their fate after they have crossed the cell membrane. Here we present a method of surface modification of silicon-substituted hydroxyapatite (SiHA) through a silane group, which enables the engraftment of a fluorescent dye to facilitate real-time biological tracking.

An analytical Micro CT methodology for quantifying inorganic dentine debris following internal tooth preparation.

Objectives: MicroCT allows the complex canal network of teeth to be mapped but does not readily distinguish between structural tissue (dentine) and the debris generated during cleaning. The aim was to introduce a validated approach for identifying debris following routine instrumentation and disinfection.

Methods: The mesial canals of 12 mandibular molars were instrumented, and irrigated with EDTA and NaOCl.

Synthetic decapeptide reduces bacterial load and accelerates healing in the wounds of restraint-stressed mice.

Wound healing is a complex process involving four transitional yet concurrent stages: coagulation, inflammation, cell proliferation/epithelialization and remodeling. These overlapping stages occur uneventfully in normal physiology. However, during psychological stress, the inflammatory response can become dysregulated and result in increased susceptibility to bacterial infection and delayed wound closure.

Antimicrobial decapeptide KSL-W enhances neutrophil chemotaxis and function.

Mammalian cationic antimicrobial peptides have received increased attention over the last decade, due to their prokaryotic selectivity and decreased risk of microbial resistance. In addition, antimicrobial peptides display differential biological effects on mammalian immune cell function, such as migration, adhesion, and modulation of respiratory burst, which make them even more attractive as therapeutic agents. Synthetic combinatorial libraries provide a time-efficient and cost-effective source for these diverse molecules.

Ala42S100A8 ameliorates psychological-stress impaired cutaneous wound healing.

Although wound healing is generally a successful, carefully orchestrated and evolutionary sound process, it can be disregulated by extrinsic factors such as psychological-stress. In the SKH-1 restraint stress model of cutaneous wound healing, the rate of wound closure is approximately 30% slower in stressed mice. Delay in healing is associated with exaggerated acute inflammation and deficient bacterial clearance at the wound site.