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. By applying shear to newly forming materials, it is possible to trigger molecular reorganization of polymer chains, such that they aggregate to form particles and ribbon-like structures. These structures then weakly interact at zero shear forming a solid-like material. The resulting self-healing network is of particular use for a range of different biomedical applications. How these materials are used to allow the delivery of therapeutic entities (cells and proteins) and as a support for additive layer manufacturing of larger-scale tissue constructs is discussed. This technology enables the development of a range of novel materials and structures for tissue augmentation and regeneration.

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. The technology reported here is a dual AMP coating. The dual coating consists of AMPs covalently bonded to the hydroxyapatite surface, followed by deposition of electrostatically bound AMPs. The dual approach gives an efficacious coating which is stable for over 12 months and can prevent colonization of the surface by both Gram-positive and Gram-negative bacteria.

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. We aimed to determine if there were individual differences in the immune response to wear debris that might indicate a poor outcome with a CoCrMo prosthesis. Blood from 22 donors was incubated with CoCrMo particles (>99.9% less than 10 µm diameter) generated by a wear simulator for 24 h. T cell phenotype was assessed by immunostaining and secretion of 8 different pro- and anti-inflammatory cytokines was measured using multiplex technology. Clear differences were seen between individuals in the induction of Th17 and Th1 responses, with some donors showing pro-inflammatory responses (increased IL17 or IFNγ) and others showing anti-inflammatory responses (decreased IL17 or IFNγ). The only differences seen for gender and age related to increased IL-10 expression from T cells in females (p = 0.008) and a trend towards decreased IL-6 expression systemically for older donors (p = 0.058). We conclude that individuals show differential responses to CoCrMo wear debris and that these responses could give early indications of the suitability of the patient for a metal-on-metal prosthesis.

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. Here we test this hypothesis by growing a population of MC3T3 osteoblast-like cells on the surface of two types of hip prosthesis with similar composition, but with differing crystallinity. The surfaces with lower crystallinity facilitated more rapid cell attachment and increased proliferation rate, despite having a less heterogeneous surface topography. This work highlights that the influence of the crystallinity of HA at the nano-scale is dominant over macro-scale topography for cell adhesion and growth. Furthermore, crystallinity could be easily adjusted by without compromising coating purity. These findings could facilitate designing novel coated calcium phosphate surfaces that more rapidly bond tissue following implantation.

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. MicroCT images before and after instrumentation and images were assessed qualitatively and quantitatively. RESULTS: Debris in the canal space was identified through morphological image analysis and superimposition of the images before and after instrumentation. This revealed that the removal of debris is prohibited by protrusions and micro-canals within the tooth creating areas which are inaccessible to the irrigant. Although the results arising from the analytical methodology did provide measurements of debris produced, biological differences in the canals resulted in variances. Both irrigants reduced debris compared to the control which decreased with EDTA and further with NaOCl. However, anatomical variation did not allow definitive conclusions on which irrigant was best to use although both reduced debris build up. CONCLUSIONS: This work presents a new approach for distinguishing between debris and structural inorganic tissue in root canals of teeth. The application may prove useful in other calcified tissue shape determination. CLINICAL SIGNIFICANCE: Remaining debris may contain bacteria and obstruct the flow of irrigating solutions into lateral canal anatomy. This new approach for detecting the amount of remaining debris in canal systems following instrumentation provides a clearer methodology of the identification of such debris.