Competition and interaction of polydisperse bubbles in polymer foams

The e®ects of interactions between bubbles of di®erent sizes during bubble growth in a polymeric foam are investigated. Two models are used: a two-dimensional sim-ulation in which both the e®ects of gas di®usion through the polymer and bubble interactions through °uid stresses are included, and a three-dimensional model in which bubbles are assumed to interact only through direct competition for gas, and di®usion of gas into the bubbles is instantaneous. In the two-dimensional model, two di®erent bubble sizes are used in a hexagonal array. For slow gas di®usion, the additional polymer stresses have little e®ect on the ¯nal bubble size distribution. For faster gas di®usion the growth occurs in two phases, just as was found in earlier work for isolated bubbles: an initial rapid viscous phase and a later phase controlled by the rate of polymer relaxation. In this later phase, polymers in the windows between neighbouring bubbles become highly stretched and these regions of high stress determine the dynamics of the growth. In the three-dimensional model we consider the e®ects of rheology on a pair of di®erent-sized spherical bubbles, interacting only through competition for available gas. Viscoelastic e®ects result in a wider distribution of bubble volumes than would be found for a Newtonian °uid. Key words: Polymeric °uid; bubble growth; foam; bubble interactions; size distribution ¤ To whom correspondence should be addressed

Examination of adipocere formation in a cold water environment

Adipocere is a late-stage postmortem decomposition product that forms from the lipids present in soft tissue. Its formation in aquatic environments is typically related to the presence of a moist, warm, anaerobic environment, and the effect of decomposer microorganisms. The ideal temperature range for adipocere formation is considered to be 21-45°C and is correlated to the optimal conditions for bacterial growth and enzymatic release. However, adipocere formation has been reported in cooler aquatic environments at considerable depths. This study aimed to investigate the chemical process of adipocere formation in a cold freshwater environment in Lake Ontario, Canada. Porcine tissue was used as a human tissue analogue and submerged at two depths (i.e., 10 and 30 feet) in the trophogenic zone of the lake. Samples were collected at monthly postmortem submersion intervals and analysed using diffuse reflectance infrared Fourier transform spectroscopy to provide a qualitative profile of the lipid degradation and adipocere formation process. Early stage adipocere formation occurred rapidly in the cold water environment and proceeded to intermediate stage adipocere formation by the second month of submersion. However, further adipocere formation was inhibited in the third month of the study when temperatures approached the freezing point. The depth of submergence did not influence the chemical conversion process as similar stages of adipocere formation occurred at both depths investigated. The study demonstrated that adipocere can form rapidly, even on small amounts of soft tissue, which may be representative of dismembered or disarticulated limbs discovered in an aquatic environment. © 2010 Springer-Verlag

Investigation of static zones and wall slip through sequential ram extrusion of contrasting micro-crystalline cellulose-based pastes

The shape and size of static regions in the extrusion flow of a viscoplastic material through axisymmetric square entry dies was studied experimentally using a simple flow field analysis technique. A white micro-crystalline cellulose/water paste was extruded sequentially with a graphite-stained black analogue paste, revealing static regions in the corners of the system extending less than 30% of the barrel radius into the centre of the channel. Slow (relative to the bulk) slip flow along the die face was evident in the experiments, implying the existence of a stick-slip transition on this surface. Finite element simulations using the Papanastasiou regularised Bingham plastic viscosity model and the linear Navier wall slip law were found to reproduce the experimental results poorly, capturing only separately the slip dominated bulk flow and the static corner region for different values of the slip coefficient _. The effect of severe wall slip was to reduce the distinction between unyielded and yielded material making the definition of the yield surface challenging. Investigation and implementation of a stick-slip wall condition is believed to be required for further work in this area.This is the author's accepted manuscript. The final version is available from Elsevier in the Journal of Non-Newtonian Fluid Mechanics here: http://www.sciencedirect.com/science/article/pii/S0377025714001207

Rotator Cuff Repair Augmentation Using Osteoinductive Growth Factors

Rotator cuff injuries (RCIs) present a major health problem due to high incidences of degenerative tears greater than 3 cm and prevalence of re-tears following surgical procedures. Since healing and functional restoration relies upon bone ingrowth into the tendon, it is hypothesised that sustained delivery of osteoinductive factors including bone morphogenetic proteins (BMPs), specifically BMP2–7, may significantly improve RCI tendon-bone healing. Here, growth factor candidates and delivery mechanisms are reviewed, specifically for improved RCI healing through enhanced bone ingrowth. In addition to BMPs, other potentially osteogenic factors including platelet-derived growth factors (PDGF), fibroblast growth factor (FGF), transforming growth beta isoforms (TGF-β1 and TGF-3) and parathyroid hormone (PTH) are evaluated since they can induce bone formation at the healing tendon attachment site. Several challenges must be addressed prior to clinical translation. The majority of published studies utilise in vivo animal models. In general, BMP-7 demonstrates a stronger stimulating effect when compared to BMP-2; the reported effectiveness of BMP-2 is often conflicting. Alternative factors, including PDGF and PTH, also demonstrate potential for assisting bone growth in enthesis healing. The use of sustained and biomimetic delivery systems appears to have the greatest positive effects. Some studies have demonstrated a dose-dependent effect, in conjunction with varying age, indicating that stratified therapies could be a viable solution for RCI healing. To adequately resolve potential treatments for RCI, further expanded and correlated animal trials must be undertaken, and indicative human trials are required with consideration of surgical and patient-specific influences

Flow visualisation and modelling of solid soap extrusion

Ram extrusion of a solid granular soap was studied using three geometrically identical but differently-scaled extruders. The experimental design revealed deviation from the Benbow and Bridgwater (1993) extrusion model due to nonideal, scale-dependent effects. Typically these effects, linked to the shear rate in the extruder, are absorbed into the model's material pseudo-properties. The data were able to be represented using the Basterfield et al. (2005) model for extrusion flow which does include a shear rate as a variable. Flow visualisation in conjunction with fluid dynamics-based simulations showed, however, that the assumptions underlying the Basterfield et al. model are not appropriate for soap extrusion, despite the good agreement of the model with the experimental extrusion data. This highlights a need for care in interpretation of extrusion data, in that the limited information gathered about any given experiment, typically just the extrusion pressure, can lead to the generation of spurious parameters if the wrong model is applied.This work was funded by Ceratizit GmbH Austria and Sandvik Hyperion U

Intraarticular injection of bone marrow-derived mesenchymal stem cells enhances regeneration in knee osteoarthritis.

PURPOSE: This review aimed to evaluate the efficacy of intra-articular injections of bone marrow derived mesenchymal stem cells (BM-MSCs) for the treatment of knee osteoarthritis (KOA). METHODS: This narrative review evaluates recent English language clinical data and published research articles between 2014 and 2019. Key word search strings of ((("bone marrow-derived mesenchymal stem cell" OR "bone marrow mesenchymal stromal cell" OR "bone marrow stromal cell")) AND ("osteoarthritis" OR "knee osteoarthritis")) AND ("human" OR "clinical"))) AND "intra-articular injection" were used to identify relevant articles using PMC, Cochrane Library, Web Of Science and Scopus databases. RESULTS: Pre-clinical studies have demonstrated successful, safe and encouraging results for articular cartilage repair and regeneration. This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of BM-MSCs, which have shown to augment pain and improve functional outcomes. Subsequently, clinical applications of intra-articular injections of BM-MSCs are steadily increasing, with most studies demonstrating a decrease in poor cartilage index, improvements in pain, function and Quality of Life (QoL); with moderate-to-high level evidence regarding safety for therapeutic administration. However, low confidence in clinical efficacy remains due to a plethora of heterogenous methodologies utilised, resulting in challenging study comparisons. A moderate number of cells (40 × 106) were identified as most likely to achieve optimal responses in individuals with grade ≥ 2 KOA. Likewise, significant improvements were reported when using lower (24 × 106) and higher (100 × 106) cell numbers, although adverse effects including persistent pain and swelling were a consequence. CONCLUSION: Overall, the benefits of intra-articular injections of BM-MSCs were deemed to outweigh the adverse effects; thus, this treatment be considered as a future therapy strategy. To realise this, long-term large-scale randomised clinical trials are required to enable improved interpretations, to determine the validity of efficacy in future studies. LEVEL OF EVIDENCE: IV

The use of PRP injections in the management of knee osteoarthritis.

Osteoarthritis (OA) is a degenerative disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture that commonly affects the knee and/or hip joints. It is a major world public health problem and is predicted to increase rapidly with an ageing population and escalating rate of obesity. Autologous blood-derived products possess much promise in the repair and regeneration of tissue and have important roles in inflammation, angiogenesis, cell migration and metabolism in pathological conditions, including OA. Utilising platelet-rich plasma (PRP) to treat tendon, ligament and skeletal muscle has shown variable results across many studies with the current evidence base for the efficacy of PRP in treating sports injuries remaining inconclusive. More uniformly positive results have been observed by various studies for PRP in OA knee in comparison to hyaluronic acid, other intra-articular injections and placebo than in other musculoskeletal tissue. However, methodological concerns as well as satisfactory PRP product classification prevent the true characterisation of this treatment. Thus, further research is required to investigate how leukocyte inclusion, activation and platelet concentration affect therapeutic efficacy. Furthermore, the optimisation of timing, dosage, volume, frequency and rehabilitation strategies need to be ascertained. For knee OA management, these concerns must be addressed before this promising treatment can be widely implemented

Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing.

There is a current need for a therapy that can alleviate the social and economic burden that presents itself with debilitating and recurring musculoskeletal soft tissue injuries and disorders. Currently, several therapies are emerging and undergoing trials in animal models; these focus on the manipulation and administration of several growth factors implicated with healing. However, limitations include in vivo instability, reliance on biocompatible and robust carriers and restricted application procedures (local and direct). The aim of this paper is therefore to critically review the current literature surrounding the use of BPC 157, as a feasible therapy for healing and functional restoration of soft tissue damage, with a focus on tendon, ligament and skeletal muscle healing. Currently, all studies investigating BPC 157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic and for a plethora of soft tissues. However, to date, the majority of studies have been performed on small rodent models and the efficacy of BPC 157 is yet to be confirmed in humans. Further, over the past two decades, only a handful of research groups have performed in-depth studies regarding this peptide. Despite this, it is apparent that BPC 157 has huge potential and following further development has promise as a therapy to conservatively treat or aid recovery in hypovascular and hypocellular soft tissues such as tendon and ligaments. Moreover, skeletal muscle injury models have suggested a beneficial effect not only for disturbances that occur as a result of direct trauma but also for systemic insults including hyperkalamia and hypermagnesia. Promisingly, there are few studies reporting any adverse reactions to the administration of BPC 157, although there is still a need to understand the precise healing mechanisms for this therapy to achieve clinical realisation

A critical review of current progress in 3D kidney biomanufacturing: advances, challenges, and recommendations

The widening gap between organ availability and need is resulting in a worldwide crisis, particularly concerning kidney transplantation. Regenerative medicine options are becoming increasingly advanced and are taking advantage of progress in novel manufacturing techniques, including 3D bioprinting, to deliver potentially viable alternatives. Cell-integrated and wearable artificial kidneys aim to create convenient and efficient systems of filtration and restore elements of immunoregulatory function. Whilst preliminary clinical trials demonstrated promise, manufacturing and trial design issues and identification of suitable and sustainable cell sources have shown that more development is required for market progression. Tissue engineering and advances in biomanufacturing techniques offer potential solutions for organ shortages; however, due to the complex kidney structure, previous attempts have fallen short. With the recent development and progression of 3D bioprinting, cell positioning and resolution of material deposition in organ manufacture have never seen greater control. Cell sources for constructing kidney building blocks and populating both biologic and artificial scaffolds and matrices have been identified, but in vitro culturing and/or differentiation, in addition to maintaining phenotype and viability during and after lengthy and immature manufacturing processes, presents additional problems. For all techniques, significant process barriers, clinical pathway identification for translation of models to humans, scaffold material availability, and long-term biocompatibility need to be addressed prior to clinical realisation

Oligoclonal expansions of CD8(+) T cells in chronic HIV infection are antigen specific

Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8(+) T cells. These 'expansions', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8(+) T cells. However, due to the difficulties in studying antigen-specific T cells in vivo, it has been hard to prove that oligoclonal BV expansions are actually HIV specific. The use of tetrameric major histocompatibility complex-peptide complexes has recently enabled direct visualization of antigen-specific T cells ex vivo but has not provided information on their clonal composition. We have now made use of these tetrameric complexes in conjunction with anti-BV chain-specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8(+) T cells are HIV specific in vivo