Modernising Orodispersible Film Characterisation to Improve Palatability and Acceptability Using a Toolbox of Techniques.

Orodispersible films (ODFs) have been widely used in paediatric, geriatric and dysphagic patients due to ease of administration and precise and flexible dose adjustments. ODF fabrication has seen significant advancements with the move towards more technologically advanced production methods. The acceptability of ODFs is dependent upon film composition and process of formation, which affects disintegration, taste, texture and mouthfeel. There is currently a lack of testing to accurately assess ODFs for these important acceptability sensory perceptions. This study produced four ODFs formed of polyvinyl alcohol and sodium carboxymethylcellulose using 3D printing. These were assessed using three in vitro methods: Petri dish and oral cavity model (OCM) methods for disintegration and bio-tribology for disintegration and oral perception. Increasing polymer molecular weight (MW) exponentially increased disintegration time in the Petri dish and OCM methods. Higher MW films adhered to the OCM upper palate. Bio-tribology analysis showed that films of higher MW disintegrated quickest and had lower coefficient of friction, perhaps demonstrating good oral perception but also stickiness, with higher viscosity. These techniques, part of a toolbox, may enable formulators to design, test and reformulate ODFs that both disintegrate rapidly and may be better perceived when consumed, improving overall treatment acceptability.

Tribological evaluation of a novel hybrid for repair of articular cartilage defects.

The friction and wear properties of silica/poly(tetrahydrofuran)/poly(ε-caprolactone) (SiO2/PTHF/PCL-diCOOH) hybrid materials that are proposed as cartilage tissue engineering materials were investigated against living articular cartilage. A testing rig was designed to allow testing against fresh bovine cartilage. The friction force and wear were compared for five compositions of the hybrid biomaterial articulating against freshly harvested bovine cartilage in diluted bovine calf serum. Under a non-migrating contact, the friction force increased and hence shear force applied to the opposing articular cartilage also increased, resulting in minor damage to the cartilage surface. This worse case testing scenario was used to discriminate between material formulations and revealed the increase in friction and damaged area was lowest for the hybrid containing the most silica. Further friction and wear tests on one hybrid formulation with an elastic modulus closest to that of cartilage were then conducted in a custom incubator system. This demonstrated that over a five day period the friction force, cell viability and glucosaminoglycan (GAG) release into the lubricant were similar between a cartilage-cartilage interface and the hybrid-cartilage interface, supporting the use of these materials for cartilage repair. These results demonstrate how tribology testing can play a part in the development of new materials for chondral tissue engineering. STATEMENT OF SIGNIFICANCE: Designing materials that maintain the low friction and wear of articular cartilage whilst supporting the growth of new tissue is critical if further damage is to be avoided during repair of cartilage defects. This work examines the tribological performance of a SiO2/PTHF/PCL-diCOOH hybrid material and demonstrates a testing protocol that could be applied to any proposed material for cartilage regeneration. Tribological tests demonstrated that changing the hybrid composition decreased friction and reduced damage to the cartilage counterface. This study demonstrates how tribological testing can be integrated into the design process to produce materials with a higher chance of clinical success.

Measurement of molten chocolate friction under simulated tongue-palate kinematics: Effect of cocoa solids content and aeration.

The perception of some food attributes is related to mechanical stimulation and friction experienced in the tongue-palate contact during mastication. This paper reports a new bench test to measure friction in the simulated tongue-palate contact. The test consists of a flat PDMS disk, representing the tongue loaded and reciprocating against a stationary lower glass surface representing the palate. The test was applied to molten chocolate samples with and without artificial saliva. Friction was measured over the first few rubbing cycles, simulating mechanical degradation of chocolate in the tongue-palate region. The effects of chocolate composition (cocoa solids content ranging between 28 â€‹wt% and 85 â€‹wt%) and structure (micro-aeration/non-aeration 0-15 â€‹vol%) were studied. The bench test clearly differentiates between the various chocolate samples. The coefficient of friction increases with cocoa solids percentage and decreases with increasing micro-aeration level. The presence of artificial saliva in the contact reduced the friction for all chocolate samples, however the relative ranking remained the same.

A lubrication replenishment theory for hydrogels.

Hydrogels are suggested as less invasive alternatives to total joint replacements, but their inferior tribological performance compared to articular cartilage remains a barrier to implementation. Existing lubrication theories do not fully characterise the friction response of all hydrogels, and a better insight into the lubrication mechanisms must be established to enable optimised hydrogel performance. We therefore studied the lubricating conditions in a hydrogel contact using fluorescent imaging under simulated physiological sliding conditions. A reciprocating configuration was used to examine the effects of contact dimension and stroke length on the lubricant replenishment in the contact. The results show that the lubrication behaviour is strongly dependent on the contact configurations; When the system operates in a 'migrating' configuration, with the stroke length larger than the contact width, the contact is uniformly lubricated and shows low friction; When the contact is in an 'overlapping' configuration with a stroke length smaller than the contact width, the contact is not fully replenished, resulting in high friction. The mechanism of non-replenishment at small relative stroke length was also observed in a cartilage contact, indicating that the theory could be generalised to soft porous materials. The lubrication replenishment theory is important for the development of joint replacement materials, as most physiological joints operate under conditions of overlapping contact, meaning steady-state lubrication does not necessarily occur.

Fluid load support does not explain tribological performance of PVA hydrogels.

The application of hydrogels as articular cartilage (AC) repair or replacement materials is limited by poor tribological behaviour, as it does not match that of native AC. In cartilage, the pressurisation of the interstitial fluid is thought to be crucial for the low friction as the load is shared between the solid and liquid phase of the material. This fluid load support theory is also often applied to hydrogels. However, this theory has not been validated as no experimental evidence directly relates the pressurisation of the interstitial fluid to the frictional response of hydrogels. This lack of understanding about the governing tribological mechanisms in hydrogels limits their optimised design. Therefore, this paper aims to provide a direct measure for fluid load support in hydrogels under physiologically relevant sliding conditions. A photoelastic method was developed to simultaneously measure the load on the solid phase of the hydrogel and its friction coefficient and thus directly relate friction and fluid load support. The results showed a clear distinction in frictional behaviour between the different test conditions, but results from photoelastic images and stress-relaxation experiments indicated that fluid load support is an unlikely explanation for the frictional response of the hydrogels. A more appropriate explanation, we hypothesized, is a non-replenished lubricant mechanism. This work has important implications for the tribology of cartilage and hydrogels as it shows that the existing theories do not adequately describe the tribological behaviour of hydrogels. The developed insights can be used to optimise the tribological performance of hydrogels as articular cartilage implants.

A low friction, biphasic and boundary lubricating hydrogel for cartilage replacement.

Partial joint repair is a surgical procedure where an artificial material is used to replace localised chondral damage. These artificial bearing surfaces must articulate against cartilage, but current materials do not replicate both the biphasic and boundary lubrication mechanisms of cartilage. A research challenge therefore exists to provide a material that mimics both boundary and biphasic lubrication mechanisms of cartilage. In this work a polymeric network of a biomimetic boundary lubricant, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), was incorporated into an ultra-tough double network (DN) biphasic (water phase + polymer phase) gel, to form a PMPC triple network (PMPC TN) hydrogel with boundary and biphasic lubrication capability. The presence of this third network of MPC was confirmed using ATR-FTIR. The PMPC TN hydrogel had a yield stress of 26 MPa, which is an order of magnitude higher than the peak stresses found in the native human knee. A preliminary pin on plate tribology study was performed where both the DN and PMPC TN hydrogels experienced a reduction in friction with increasing sliding speed which is consistent with biphasic lubrication. In the physiological sliding speed range, the PMPC TN hydrogel halved the friction compared to the DN hydrogel indicating the boundary lubricating PMPC network was working. A biocompatible, tough, strong and chondral lubrication imitating PMPC TN hydrogel was synthesised in this work. By complementing the biphasic and boundary lubrication mechanisms of cartilage, PMPC TN hydrogel could reduce the reported incidence of chondral damage opposite partial joint repair implants, and therefore increase the clinical efficacy of partial joint repair. STATEMENT OF SIGNIFICANCE: This paper presents the synthesis, characterisation and preliminary tribological testing of a new biomaterial that aims to recreate the primary chondral lubrication mechanisms: boundary and biphasic lubrication. This work has demonstrated that the introduction of an established zwitterionic, biomimetic boundary lubricant can improve the frictional properties of an ultra-tough hydrogel. This new biomaterial, when used as a partial joint replacement bearing material, may help avoid damage to the opposing chondral surface-which has been reported as an issue for other non-biomimetic partial joint replacement materials. Alongside the synthesis of a novel biomaterial focused on complementing the lubrication mechanisms of cartilage, your readership will gain insights into effective mechanical and tribological testing methods and materials characterisation methods for their own biomaterials.

Real-time observation of fluid flows in tissue during stress relaxation using Raman spectroscopy.

This paper outlines a technique to measure fluid levels in articular cartilage tissue during an unconfined stress relaxation test. A time series of Raman spectrum were recorded during relaxation and the changes in the specific Raman spectral bands assigned to water and protein were monitored to determine the fluid content of the tissue. After 1000s unconfined compression the fluid content of the tissue is reduced by an average of 3.9%±1.7%. The reduction in fluid content during compression varies between samples but does not significantly increase with increasing strain. Further development of this technique will allow mapping of fluid distribution and flows during dynamic testing making it a powerful tool to understand the role of interstitial fluid in the functional performance of cartilage.

Zirconia phase transformation in retrieved, wear simulated, and artificially aged ceramic femoral heads.

Zirconia in Zirconia toughened alumina ceramic hip replacements exists in an unstable state and can transform in response to stress giving the material improved fracture toughness. Phase transformation also occurs under hydrothermal conditions such as exist in vivo. To predict the hydrothermal aging that will occur in vivo accelerated aging procedures have been used, but validation of these models requires the study of retrieved hip joints. Here 26 retrievals are analysed to determine the degree of phase transformation in vivo. These were compared with virgin heads, heads that had undergone the accelerated aging process and heads wear tested to 5 million cycles in a hip simulator. Monoclinic content and surface roughness were measured using Raman spectroscopy and white light interferometry respectively. The monoclinic content for retrieved heads was 28.5% ± 7.8, greater than twice that in virgin, aged, or wear tested heads and did not have a significant correlation with time, contrary to the predictions of the hydrothermal aging model. The surface roughness for retrieved heads in the unworn area was not significantly different to that in virgin, aged, or unworn areas of wear tested heads. However in worn areas of the retrieved heads, the surface roughness was higher than observed in wear simulator testing. These results indicate that current testing methodologies do not fully capture the operational conditions of the material and the real performance of future new materials may not be adequately predicted by current pre-clinical testing methods. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society 35:2781-2789, 2017.

The effect of transient conditions on synovial fluid protein aggregation lubrication.

Little is known about the prevailing lubrication mechanisms in artificial articular joints and the way in which these mechanisms determine implant performance. The authors propose that interfacial film formation is determined by rheological changes local to the contact and is driven by aggregation of synovial fluid proteins within the contact inlet region. A direct relationship between contact film thickness and size of the protein aggregation within the inlet region has been observed. In this paper the latest experimental observations of the protein aggregation mechanism are presented for conditions which more closely mimic joint kinematics and loading. Lubricant films were measured for a series of bovine calf serum solutions for CoCrMo femoral component sliding against a glass disc. An optical interferometric apparatus was employed to study the effects of transient motion on lubricant film formation. Central film thickness was measured as a function of time for a series of transient entrainment conditions; start-up motion, steady-state and non-steady-state uni-directional sliding, and bi-directional sliding. The size of the inlet aggregations was found to be dependent upon the type of transient condition. Thick protective protein films were observed to build up within the main contact region for all uni-directional tests. In contrast the inlet aggregation was not observed for bi-directional tests. Contact film thickness and wear was found to be directly proportional to the presence of the inlet protein phase. The inlet phase and contact films were found to be fragile when disrupted by surface scratches or subjected to reversal of the sliding direction.

On the matter of synovial fluid lubrication: implications for Metal-on-Metal hip tribology.

Artificial articular joints present an interesting, and difficult, tribological problem. These bearing contacts undergo complex transient loading and multi axes kinematic cycles, over extremely long periods of time (>10 years). Despite extensive research, wear of the bearing surfaces, particularly metal-metal hips, remains a major problem. Comparatively little is known about the prevailing lubrication mechanism in artificial joints which is a serious gap in our knowledge as this determines film formation and hence wear. In this paper we review the accepted lubrication models for artificial hips and present a new concept to explain film formation with synovial fluid. This model, recently proposed by the authors, suggests that interfacial film formation is determined by rheological changes local to the contact and is driven by aggregation of synovial fluid proteins. The implications of this new mechanism for the tribological performance of new implant designs and the effect of patient synovial fluid properties are discussed.

Effects of fiber orientation on the frictional properties and damage of regenerative articular cartilage surfaces.

Articular cartilage provides a low-friction, wear-resistant surface for diarthrodial joints. Due to overloading and overuse, articular cartilage is known to undergo significant wear and degeneration potentially resulting in osteoarthritis (OA). Regenerative medicine strategies offer a promising solution for the treatment of articular cartilage defects and potentially localized early OA. Such strategies rely on the development of materials to restore some aspects of cartilage. In this study, microfibrous poly(ɛ-caprolactone) scaffolds of varying fiber orientations (random and aligned) were cultured with bovine chondrocytes for 4 weeks in vitro, and the mechanical and frictional properties were evaluated. Mechanical properties were quantified using unconfined compression and tensile testing techniques. Frictional properties were investigated at physiological compressive strains occurring in native articular cartilage. Scaffolds were sheared along the fiber direction, perpendicular to the fiber direction and in random orientation. The evolution of damage as a result of shear was evaluated via white light interferometry and scanning electron microscopy. As expected, the fiber orientation strongly affected the tensile properties as well as the compressive modulus of the scaffolds. Fiber orientation did not significantly affect the equilibrium frictional coefficient, but it was, however, a key factor in dictating the evolution of surface damage on the surface. Scaffolds shear tested perpendicular to the fiber orientation displayed the highest surface damage. Our results suggest that the fiber orientation of the scaffold implanted in the joint could strongly affect its resistance to damage due to shear. Scaffold fiber orientation should thus be carefully considered when using microfibrous scaffolds.

Edge loading in metal-on-metal hips: low clearance is a new risk factor.

The revision rate of large head metal-on-metal and resurfacing hips are significantly higher than conventional total hip replacements. The revision of these components has been linked to high wear caused by edge loading; which occurs when the head-cup contact patch extends over the cup rim. There are two current explanations for this; first, there is loss of entrainment of synovial fluid resulting in breakdown of the lubricating film and second, edge loading results in a large local increase in contact pressure and consequent film thickness reduction at the cup rim, which causes an increase in wear. This paper develops a method to calculate the distance between the joint reaction force vector and the cup rim--the contact patch centre to rim (CPCR) distance. However, the critical distance for the risk of edge loading is the distance from the contact patch edge to rim (CPER) distance. An analysis of explanted hip components, divided into edge worn and non-edge-worn components showed that there was no statistical difference in CPCR values, but the CPER value was significantly lower for edge worn hips. Low clearance hips, which have a more conformal contact, have a larger diameter contact patch and thus are more at risk of edge loading for similarly positioned hips.

Synovial fluid lubrication of artificial joints: protein film formation and composition.

Despite design improvements, wear of artificial implants remains a serious health issue particularly for Metal-on-Metal (MoM) hips where the formation of metallic wear debris has been linked to adverse tissue response. Clearly it is important to understand the fundamental lubrication mechanisms which control the wear process. It is usually assumed that MoM hips operate in the ElastoHydrodynamic Lubrication (EHL) regime where film formation is governed by the bulk fluid viscosity; however there is little experimental evidence of this. The current paper critically examines synovial fluid lubrication mechanisms and the effect of synovial fluid chemistry. Two composition parameters were chosen; protein content and pH, both of which are known to change in diseased or post-operative synovial fluid. Film thickness and wear tests were carried out for a series of model synovial fluid solutions. Two distinct film formation mechanisms were identified; an adsorbed surface film and a high-viscosity gel. The entrainment of this gel controls film formation particularly at low speeds. However wear of the femoral head still occurs and this is thought to be due primarily to a tribo-corrosion mechanisms. The implications of this new lubrication mechanism and the effect of different synovial fluid chemistries are examined. One important conclusion is that patient synovial fluid chemistry plays an important role in determining implant wear and the likelihood of failure.