Fergal O'Brien (* 8. März ) ist ein irischer Snookerspieler. Seit ist er Profi auf der Snooker Main Tour. Inhaltsverzeichnis. 1 Karriere. Anfangsjahre . Fergal O'johaninkinen.se 1, × ; KB. 1 reference johaninkinen.senooker. com/players/fergal-obrien/ · retrieved. 7 August participant of. Das Profil von Snooker-Spieler Fergal O'Brien im Überblick mit Artikeln, Bildern, wichtigen Lebensdaten und Links.
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Overall, this study has demonstrated that the atRA-B scaffold can enhance functional epithelialisation in primary tracheobronchial cells and can potentially pioneer the development of a novel and biocompatible device to address a currently unmet clinical need in tracheal replacement.
Peripheral nerve injuries have high incidence rates, limited treatment options and poor clinical outcomes, rendering a significant socioeconomic burden.
For effective peripheral nerve repair, the gap or site of injury must be structurally bridged to promote correct reinnervation and functional regeneration.
However, effective repair becomes progressively more difficult with larger gaps. Autologous nerve grafting remains the best clinical option for the repair of large gaps 20—80 mm despite being associated with numerous limitations including permanent donor site morbidity, a lack of available tissue and the formation of neuromas.
To meet the clinical demand of large gap repair and overcome these limitations, tissue engineering has led to the development of nerve guidance conduit-based therapeutics.
This review focuses on the advances of nerve guidance conduit-based therapeutics in terms of their structural properties including biomimetic composition, permeability, architecture, and surface modifications Cardiac Stem Cells CSCs represent a logical cell type to exploit as a regenerative treatment option for tissue damage accrued as a result of a myocardial infarction MI.
However, the isolation and expansion of CSCs prior to cell transplantation is time-consuming, costly and invasive, and the reliability of cell expansion may also prove to be a major obstacle in the clinical application of CSC based transplantation therapy after a MI.
In order to overcome this, we propose the incorporation of growth factor-eluting alginate microparticles MPs into collagen-based scaffolds as an implantable biomaterial to promote the recruitment and expansion of CSCs in the myocardium.
The benefits and limitations of animal models for translational research in cartilage repair. Much research is currently ongoing into new therapies for cartilage defect repair with new biomaterials frequently appearing which purport to have significant regenerative capacity.
These biomaterials may be classified as medical devices, and as such must undergo rigorous testing before they are implanted in humans.
A large part of this testing involves in vitro trials and biomechanical testing. However, in order to bridge the gap between the lab and the clinic, in vivo preclinical trials are required, and usually demanded by regulatory approval bodies.
This review examines the in vivo models in current use for cartilage defect repair testing and the relevance of each in the context of generated results and applicability to bringing the device to clinical practice.
Some of the preclinical models currently used include murine, leporine, ovine, caprine, porcine, canine, and equine models. Each of these has advantages and disadvantages in terms of animal husbandry, cartilage thickness, joint biomechanics and ethical and licencing issues.
This review will examine the strengths and weaknesses of the various animal models currently in use in preclinical studies of cartilage repair.
In recent years, RNA interference RNAi has emerged as a potential therapeutic offering the opportunity to treat a wide range of diseases, including prostate cancer.
Modified cyclodextrins have emerged as effective gene delivery vectors in a range of disease models. The main objective of the current study was to formulate anisamide-targeted cyclodextrin nanoparticles to interact with the sigma receptor overexpressed on the surface of prostate cancer cells.
The inclusion of octaarginine in the nanoparticle optimized uptake and endosomal release of siRNA in two different prostate cancer cell lines PC3 and DU cells.
In sigma receptor-positive cell lines, the uptake of anisamide-targeted nanoparticles was reduced in the presence of the sigma receptor competitive ligand, haloperidol.
When cells were transfected in 2D, the levels of PLK1 mRNA knockdown elicited by targeted versus untargeted nanoparticles tended to be greater but the differences were not statistically different.
To our knowledge, this is the first time that a targeted cyclodextrin has been used to transfect prostate cancer cells in a 3D model of bone metastasis.
Regenerating articular cartilage and fibrocartilaginous tissue such as the meniscus is still a challenge in orthopedic medicine. While a range of different scaffolds have been developed for joint repair, none have facilitated the development of a tissue that mimics the complexity of soft tissues such as articular cartilage.
Furthermore, many of these scaffolds are not designed to function in mechanically challenging joint environments. The overall goal of this study was to develop a porous, biomimetic, shape-memory alginate scaffold for directing cartilage regeneration.
To this end, a scaffold was designed with architectural cues to guide cellular and neo-tissue alignment, which was additionally functionalized with a range of extracellular matrix ECM cues to direct stem cell differentiation towards the chondrogenic lineage.
Shape-memory properties were introduced by covalent crosslinking alginate using carbodiimide chemistry, while the architecture of the scaffold was modified using a directional freezing technique.
Introducing such an aligned pore structure was found to improve the mechanical properties of the scaffold, and promoted higher levels of sGAG and collagen deposition compared to an isotropic non-aligned pore geometry when seeded with adult human stem cells.
Functionalization with collagen improved stem cell recruitment into the scaffold and facilitated more homogenous cartilage tissue deposition throughout the construct.
Incorporating type II collagen into the scaffolds led to greater cell proliferation, higher sGAG and collagen accumulation, and the development of a stiffer tissue compared to scaffolds functionalized with type I collagen.
The results of this study demonstrate how both scaffold architecture and composition can be tailored in a shape-memory alginate scaffold to direct stem cell differentiation and support the development of complex cartilaginous tissues.
A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents. This paper details the development of a heat responsive liposome loaded hydrogel for the controlled release of pro-angiogenic therapeutics.
Lysolipid-based thermosensitive liposomes LTSLs embedded in a chitosan-based thermoresponsive hydrogel matrix represents a novel approach for the spatiotemporal release of therapeutic agents.
This hydrogel platform demonstrates remarkable flexibility in terms of drug scheduling and sequencing, enabling the release of multiple agents and the ability to control drug dosing in a minimally invasive fashion.
The possibility to tune the release kinetics of different drugs independently represents an innovative platform to utilise for a variety of treatments.
This approach allows a significant degree of flexibility in achieving a desired release profile via a minimally invasive stimulus, enabling treatments to be tuned in response to changing symptoms and complications.
Content-Dependent Osteogenic Response of Nanohydroxyapatite: The use of collagen-based scaffolds in orthopedic applications has been limited due to poor mechanical properties, but this may be overcome by the introduction of a stiffer supporting phase.
Thus, we have developed a synthesis technique to produce non-aggregating, stable nano-hydroxyapatite nHA particles, permitting the fabrication of biomimetic-inspired scaffolds through the combination of nano-sized HA with collagen, as found in native bone.
This study evaluates the mechanical and biological impact of incorporating increasing concentrations of these nanoparticles into porous collagen scaffolds 1: Mechanical assessment demonstrated that increasing nHA incorporation correlated with increasing Young's moduli, which could be further amplified using cross-linking treatments.
Typically, the porosity of a scaffold is sacrificed to produce a stiffer material; however, through the use of nano-sized particles the inclusion of up to 5: Moreover, increasing nHA presence induced significant bioactive responses, achieving superior cellular attachment and enhanced osteogenesis, promoting earlier expression of bone markers and cell-mediated mineralization vs.
Interestingly, these content-dependent results observed in vitro did not directly translate in vivo. Instead, similar levels of bone formation were achieved within critical-sized rat calvarial defects, independent of nHA content, following acellular implantation.
The addition of nHA, both 1: Ultimately, these results demonstrate the immense osteoinductivity of non-aggregated nanoparticles of HA incorporated into collagen-composite scaffolds, and emphasizes the importance of in vivo-based evaluation of therapies intended for clinical use.
Nanoparticle-mediated siRNA delivery assessed in a 3D co-culture model simulating prostate cancer bone metastasis.
This study aimed to develop and characterise a 3D in vitro co-culture model to simulate prostate cancer bone metastasis and to assess the ability of the model to investigate nanoparticle-mediated siRNA delivery and gene knockdown.
To characterise the co-culture model, cell proliferation, enzyme secretion and the utility of two different gene delivery vectors to mediate siRNA uptake and gene knockdown were assessed.
Results indicate that the prostate cancer-osteoblast in vitro co-culture model was more physiologically relevant versus the monoculture.
This model has the potential to help improve the design and efficacy of gene delivery formulations, to more accurately predict in vivo performance and, therefore, to reduce the risk of product failure in late-stage clinical development.
Stem cells display a donor dependent response to escalating levels of growth factor release from extracellular matrix-derived scaffolds: Stem cells display a donor dependent response to escalating levels of growth factor.
Numerous growth factor delivery systems have been developed for tissue engineering. However, little is known about how the dose of a specific protein will influence tissue regeneration, or how different patients will respond to altered levels of growth factor presentation.
After seeding these scaffolds with human infrapatellar fat pad-derived stem cells FPSCs , it was found that cartilage-specific ECM accumulation was greatest for the higher levels of growth factor loading.
Similar results were observed for FPSCs from all donors, although the absolute level of secreted matrix did vary from donor to donor.
Jul BMC Proceedings. Validity of clinical assessment compared with plantar fascia thickness on ultrasound for plantar fasciitis: Positive fluid balance as a prognostic factor in children with sepsis during first 3 hours of resuscitation in intensive care unit Linda Sirone, Renars Erts, Jana Pavare P3: Too little or too much?
Endoscopic retrograde cholangiopancreatography in the west of Ireland: Imaging proteasomal inhibition after seizures in the brain: Granular analysis of causes of peritoneal dialysis technique failure in the first six months of therapy Richard Bresler, Zita Abreu, Stefan Trohonel, Joanne Bargman P Job satisfaction of surgeons working in hajj pilgrimage: Is it possible to predict resistance of an organism to stress based on the level of corticosterone?
Mariia Zharova, Pavel Umrukhin P Does bladder drainage with intermittent catheterisation preserve kidney function in boys with posterior urethral valves?
Investigating the role of Stonin 2, a Clathrin Mediated Endocytosis adaptor protein, in altered hippocampal synaptic transmission characterized in schizophrenia Marina Yostos, David Cotter, Melanie Focking P Incidental glucose and lipid metabolisms disorders among office workers: Diagnosis and control of hypertension as indicators of the level of awareness among relatives of medical students Ahmad A.
Study of the variability of glucose levels in patients with diabetes undergoing continuous glucose monitoring Paraic Behan, Seamus Sreenan P Carroll, Laura Fee, Noel G.
Multifunctional Biomaterials from the Sea: Natural biomaterials such as collagen show promise in tissue engineering applications due to their inherent bioactivity.
The main limitation of collagen is its low mechanical strength and somewhat unpredictable and rapid degradation rate; however, combining collagen with another material, such as chitosan, can reinforce the scaffold mechanically and may improve the rate of degradation.
Additionally, the high cost and the risk of prion transmission associated with mammal-derived collagen has prompted research into alternative sources such as marine-origin collagen.
In this context, the overall goal of this study was to determine if the incorporation of chitosan into collagen scaffolds could improve the mechanical and biological properties of the scaffold.
In addition the study assessed if collagen, derived from salmon skin marine , can provide an alternative to collagen derived from bovine tendon mammal for tissue engineering applications.
Scaffold architecture and mechanical properties were assessed as well as their ability to support mesenchymal stem cell growth and differentiation.
Overall, the addition of chitosan to bovine and salmon skin-derived collagen scaffolds improved the mechanical properties, increasing the compressive strength, swelling ratio and prolonged the degradation rate.
Mesenchymal stem cell MSC attachment and proliferation was most improved on the bovine-derived collagen scaffold containing a Regardless of chitosan content, the bovine-derived collagen scaffolds out-performed the salmon skin-derived collagen scaffolds, displaying a larger pore size and higher percentage porosity, more regular architecture, higher compressive modulus, a greater capacity for water uptake and allowed for more MSC proliferation and differentiation.
This versatile scaffold incorporating the marine biomaterial chitosan show great potential as appropriate platforms for promoting orthopaedic tissue repair while the use of salmon skin-derived collagen may be more suitable in the repair of soft tissues such as skin.
Collagen is commonly used in tissue engineering due to its biocompatibility; however, it has low mechanical strength and an unpredictable degradation rate.
In addition, high cost and risk of prion transmission associated with mammalian-derived collagen has prompted research into alternative collagen sources, namely, marine-derived collagen.
In this study, scaffolds made from salmon-skin collagen were compared to the more commonly used bovine-derived collagen with a focus on orthopaedic applications.
To improve the mechanical properties of these scaffolds, another marine biomaterial, chitosan, was added to produce scaffolds with increased mechanical stability.
The collagen-chitosan composites were also shown to support mesenchymal stem cell differentiation towards both bone and cartilage tissue.
This multi-functional scaffold therefore has potential in both bone and cartilage regeneration applications.
MSC fate following non-viral transfection with therapeutic genes strongly depends on the choice of gene delivery vector. Alginate hydrogels incorporating cell penetrating peptide-mediated gene delivery for cartilage tissue engineering.
This could potentially be achieved in vivo through the delivery of regulatory genes. Essential to effective gene delivery is the choice of gene carrier.
Non-viral delivery vectors have been extensively used in TE but their intrinsic effects on MSC differentiation remain relatively unexplored.
Therefore the objective of this study was to investigate the influence of three different nonviral gene delivery vectors polyethylenimine PEI , nanohydroxyapatite nHA and RALA peptide on modulating stem cell fate after the delivery of genes encoding for chondrogenic and osteogenic growth factors.
Next generation bone tissue engineering: Non-viral miRa inhibition using collagen-nanohydroxyapatite scaffolds rapidly enhances osteogenesis.
The influence of microRNAs in the regenerative capacity of stem cells offers vast therapeutic potential towards bone grafting; however their efficient delivery to the target site remains a major challenge.
This study describes how the functionalisation of porous collagen-nanohydroxyapatite nHA scaffolds with miRa inhibiting complexes, delivered using non-viral nHA particles, enhanced human mesenchymal stem cell-mediated osteogenesis through the novel focus on a key activator of osteogenesis, Runx2.
This study showed enhanced Runx2 and osteocalcin expression, as well as increased alkaline phosphatase activity and calcium deposition, thus demonstrating a further enhanced therapeutic potential of a biomaterial previously optimised for bone repair applications.
The promising features of this platform offer potential for a myriad of applications beyond bone repair and tissue engineering, thus presenting a new paradigm for microRNA-based therapeutics.
Repair of large osteochondritis dissecans lesions using a novel multilayered tissue engineered construct in an equine athlete: Repair of large OCD lesions in a horse.
Osteochondral lesions resulting from osteochondritis dissecans are problematic to treat and present a significant challenge for clinicians.
The aims of this study were to investigate the use of a scaffold-assisted microfracture approach, employing a novel, multilayered, collagen-based, osteochondral graft substitute in the treatment of severe osteochondritis dissecans of both lateral femoral trochlear ridges in an equine athlete, and to assess the potential of this novel scaffold to enhance repair of the osteochondral unit.
A 15 month-old female filly presented with large osteochondritis dissecans lesions involving both femoral lateral trochlear ridges.
After routine arthroscopic debridement and microfracture of the subchondral bone, multilayered osteochondral defect repair scaffolds were implanted into the fragmentation beds in both left and right femoropatellar joints via mini-arthrotomies.
Exploratory arthroscopy 5 months postimplantation revealed smooth cartilaginous repair tissue, contiguous with the adjacent cartilage, covering the defect.
At month follow up, the filly had no signs of lameness and was exercising at her intended level. Radiographically, although still slightly flattened, the femoral trochlear ridges were smooth, with no evidence of osteoarthritis.
Ultrasonographically, the defects were filled with bone and covered with an overlying cartilaginous layer, with the trochlear ridge contour almost entirely restored.
This report demonstrates the effective clinical use of this novel, multilayered, osteochondral defect repair scaffold in the treatment of osteochondritis dissecans of an equine athlete.
The successful repair achieved here using this novel scaffold in an equine patient with large bilateral lesions shows the potential for clinical translation in the treatment of human patients presenting with osteochondral defects.
Incorporating therapeutic genes into 3D biomaterials is a promising strategy for enhancing tissue regeneration.
Alginate hydrogels have been extensively investigated for cartilage and bone tissue engineering, including as carriers of transfected cells to sites of injury, making them an ideal gene delivery platform for cartilage and osteochondral tissue engineering.
The objective of this study was to develop gene-activated alginate hydrogels capable of supporting nanohydroxyapatite nHA -mediated non-viral gene transfer to control the phenotype of mesenchymal stem cells MSCs for either cartilage or endochondral bone tissue engineering.
Initial analysis using reporter genes showed effective gene delivery and sustained overexpression of the transgenes was achieved.
Confocal microscopy demonstrated that complexing the plasmid with nHA prior to hydrogel encapsulation led to transport of the plasmid into the nucleus of MSCs, which did not happen with naked pDNA.
Towards 3D in vitro models for the study of cardiovascular tissues and disease. The field of tissue engineering is developing biomimetic biomaterial scaffolds that are showing increasing therapeutic potential for the repair of cardiovascular tissues.
However, a major opportunity exists to use them as 3D in vitro models for the study of cardiovascular tissues and disease in addition to drug development and testing.
These in vitro models can span the gap between 2D culture and in vivo testing, thus reducing the cost, time, and ethical burden of current approaches.
Here, we outline the progress to date and the requirements for the development of ideal in vitro 3D models for blood vessels, heart valves, and myocardial tissue.
An alternative to the use of in vitro expanded cells in regenerative medicine is the use of freshly isolated stromal cells, where a bioactive scaffold or hydrogel is used to provide an environment that enhances their proliferation and tissue-specific differentiation in vivo.
This study demonstrates that freshly isolated stromal cells generate cartilage tissue in vivo when incorporated into such a fibrin hydrogels functionalized with cartilage ECM particles.
These findings open up new possibilities for intheatre, single-stage, cell-based therapies for joint regeneration.
An endochondral ossification-based approach to bone repair: Chondrogenically-primed MSC-laden scaffolds support greater repair of critical-sized cranial defects than osteogenically stimulated constructs in vivo.
The lack of success associated with the use of bone grafts has motivated the development of tissue engineering approaches for bone defect repair.
However, the traditional tissue engineering approach of direct osteogenesis, mimicking the process of intramembranous ossification IMO leads to poor vascularisation.
In this study, we speculate that mimicking an endochondral ossification ECO approach may offer a solution by harnessing the potential of hypertrophic chondrocytes to secrete angiogenic signals that support vasculogenesis and enhance bone repair.
We hypothesised that stimulation of mesenchymal stem cell MSC chondrogenesis and subsequent hypertrophy within collagen-based scaffolds would lead to improved vascularisation and bone formation when implanted within a critical-sized bone defect in vivo.
To produce ECO-based constructs, two distinct scaffolds, collagen-hyaluronic acid and collagen-hydroxyapatite, with proven potential for cartilage and bone repair respectively, were cultured with MSCs initially in the presence of chondrogenic factors and subsequently supplemented with hypertrophic factors.
To produce IMO-based constructs, collagen-hydroxyapatite scaffolds were cultured with MSCs in the presence of osteogenic factors. These constructs were subsequently implanted into 7 mm calvarial defects on Fischer male rats for up to 8 weeks in vivo.
The results demonstrated that IMO- and ECO-based constructs were capable of supporting enhanced bone repair compared to empty defects.
We speculate this to be associated with the secretion of angiogenic signals as demonstrated by the higher VEGF protein production in the ECO-based constructs prior to implantation leading the greater blood vessel ingrowth.
This study thus demonstrates the ability of recapitulating a developmental process of bone formation to develop tissue-engineered constructs that manifest appreciable promise for bone defect repair.
Challenges, Progress and Future Perspectives. As well as acting to fill defects and allow for cell infiltration and proliferation in regenerative medicine, biomaterial scaffolds can also act as carriers for therapeutics, further enhancing their efficacy.
Drug and protein delivery on scaffolds have shown potential, however, supraphysiological quantities of therapeutic are often released at the defect site, causing off-target side effects and cytotoxicity.
Gene therapy involves the introduction of foreign genes into a cell in order to exert an effect; either replacing a missing gene or modulating expression of a protein.
State of the art gene therapy also encompasses manipulation of the transcriptome by harnessing RNA interference RNAi therapy. The delivery of nucleic acid nanomedicines on biomaterial scaffolds - gene-activated scaffolds -has shown potential for use in a variety of tissue engineering applications, but as of yet, have not reached clinical use.
The current state of the art in terms of biomaterial scaffolds and delivery vector materials for gene therapy is reviewed, and the limitations of current procedures discussed.
Future directions in the clinical translation of gene-activated scaffolds are also considered, with a particular focus on bone and cartilage tissue regeneration.
DNA origami is a DNA-based nanotechnology that utilizes programmed combinations of short complementary oligonucleotides to fold a large single strand of DNA into precise 2D and 3D shapes.
The exquisite nanoscale shape control of this inherently biocompatible material is combined with the potential to spatially address the origami structures with diverse cargoes including drugs, antibodies, nucleic acid sequences, small molecules, and inorganic particles.
This programmable flexibility enables the fabrication of precise nanoscale devices that have already shown great potential for biomedical applications such as: Here, the advances in the DNA-origami field since its inception several years ago are reviewed with a focus on how these DNA-nanodevices can be designed to interact with cells to direct or probe their behavior.
The cellular and molecular basis of vascular calcification VC in atherosclerosis is not fully understood.
In conclusion, resident vascular cells from atherosclerotic environment respond to the inflammatory milieu and undergo calcification. IL-6 may have a role in aberrant differentiation of VSCs contributing to vascular calcification in atherosclerosis.
This article is protected by copyright. Biomaterial-Enhanced Cell and Drug Delivery: Heart failure is a significant clinical issue. It is the cause of enormous healthcare costs worldwide and results in significant morbidity and mortality.
Cardiac regenerative therapy has progressed considerably from clinical and preclinical studies delivering simple suspensions of cells, macromolecule, and small molecules to more advanced delivery methods utilizing biomaterial scaffolds as depots for localized targeted delivery to the damaged and ischemic myocardium.
Here, regenerative strategies for cardiac tissue engineering with a focus on advanced delivery strategies and the use of multimodal therapeutic strategies are reviewed.
Today, chronic respiratory disease is one of the leading causes of mortality globally. Epithelial dysfunction can play a central role in its pathophysiology.
The development of physiologically-representative in vitro model systems using tissue-engineered constructs might improve our understanding of epithelial tissue and disease.
This study sought to engineer a bilayered collagen-hyaluronate CHyA-B scaffold for the development of a physiologically-representative 3D in vitro tracheobronchial epithelial co-culture model.
CHyA-B scaffolds were fabricated by integrating a thin film top-layer into a porous sub-layer with lyophilisation. The film layer firmly connected to the sub-layer with delamination occurring at stresses of kPa.
Crosslinked scaffolds had a compressive modulus of 1. Histological analysis showed that the Calu-3 bronchial epithelial cell line attached and grew on CHyA-B with adoption of an epithelial monolayer on the film layer.
Immunofluorescence and qRT-PCR studies demonstrated that the CHyA-B scaffolds facilitated Calu-3 cell differentiation, with enhanced mucin expression, increased ciliation and the formation of intercellular tight junctions.
Co-culture of Calu-3 cells with Wi38 lung fibroblasts was achieved on the scaffold to create a submucosal tissue analogue of the upper respiratory tract, validating CHyA-B as a platform to support co-culture and cellular organisation reminiscent of in vivo tissue architecture.
In summary, this study has demonstrated that CHyA-B is a promising tool for the development of novel 3D tracheobronchial co-culture in vitro models with the potential to unravel new pathways in drug discovery and drug delivery.
Developing repair strategies for osteochondral tissue presents complex challenges due to its interfacial nature and complex zonal structure, consisting of subchondral bone, intermediate calcified cartilage and the superficial cartilage regions.
In this study, the long term ability of a multi-layered biomimetic collagen-based scaffold to repair osteochondral defects is investigated in a large animal model: The study thus presents the first data in a clinically applicable large animal model.
Scaffold fixation and early integration was demonstrated at 2 weeks post implantation. Macroscopic analysis demonstrated improved healing in the multi-layered scaffold group compared to empty defects and a market approved synthetic polymer osteochondral scaffold groups at 6 and 12 months post implantation.
Radiological analysis demonstrated superior subchondral bone formation in both defect sites in the multi-layered scaffold group as early as 3 months, with complete regeneration of subchondral bone by 12 months.
Histological analysis confirmed the formation of well-structured subchondral trabecular bone and hyaline-like cartilage tissue in the multi-layered scaffold group by 12 months with restoration of the anatomical tidemark.
Demonstration of improved healing following treatment with this natural polymer scaffold, through the recruitment of host cells with no requirement for pre-culture, shows the potential of this device for the treatment of patients presenting with osteochondal lesions.
Dynamic stimulation allows development of a functional tissue engineered heart valve. Jan BioEngineering in Ireland Incorporation of polymeric microparticles into collagen-hydroxyapatite scaffolds for the delivery of a pro-osteogenic peptide for bone tissue engineering.
Collagen-hydroxyapatite scaffolds are outstanding materials for bone tissue engineering as they are biocompatible, bioresorbable, osteoconductive, and osteoinductive.
The objective of the present work was to assess the potential of increasing their regenerative capacity by functionalising the scaffolds for therapeutic delivery.
This was achieved by the utilization of polymeric drug carriers. With this purpose, alginate, chitosan, gelatine, and poly lactic-co-glycolic acid PLGA microparticles eluting PTHrP , an osteogenic pentapeptide, were fabricated and tested by incorporating them into the scaffolds.
Among them, PLGA microparticles show the most promising characteristics for use as drug delivery devices.
Following the incorporation of the microparticles, the scaffolds maintained their interconnected porous structure and the mechanical properties of the materials were not adversely affected.
In addition, the microparticles released all their PTHrP cargo. Most importantly, the delivered peptide proved to be bioactive and promoted enhanced osteogenesis as assessed by alkaline phosphatase production and osteocalcin and osteopontin gene expression when pre-osteoblastic cells were seeded on the scaffolds.
While the focus was on bone repair, the release system described in this study can be used for the delivery of therapeutics for healing and regeneration of a variety of tissue types depending on the type of collagen scaffold chosen.
Dec Matrix Biology Ireland. Form and function in regenerative medicine: Identification of a suitable treatment for osteochondral repair presents a major challenge due to existing limitations and an urgent clinical need remains for an off-the-shelf, low cost, one-step approach.
A biomimetic approach, where the biomaterial itself encourages cellular infiltration from the underlying bone marrow and provides physical and chemical cues to direct these cells to regenerate the damaged tissue, provides a potential solution.
To meet this need, a multi-layer collagen-based osteochondral defect repair scaffold has been developed in our group.
The objective of this study was to assess the in vivo response to this scaffold and determine its ability to direct regenerative responses in each layer in order to repair osteochondral tissue in a critical-sized defect in a rabbit knee.
Repair was assessed macroscopically, histologically and using micro-CT analysis at 12 weeks post implantation. Analysis of repair tissue demonstrated an enhanced macroscopic appearance in the multi-layer scaffold group compared to the empty group.
In addition, diffuse host cellular infiltration in the scaffold group resulted in tissue regeneration with a zonal organisation, with repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark.
These results demonstrate the potential of this biomimetic multi-layered scaffold to support and guide the host reparative response in the treatment of osteochondral defects.
Osteochondral defects, involving cartilage and the underlying subchondral bone, frequently occur in young active patients due to disease or injury.
While some treatment options are available, success is limited and patients often eventually require joint replacement.
To address this clinical need, a multi-layer collagen-based osteochondral defect repair scaffold designed to direct host-stem cell mediated tissue formation within each region, has been developed in our group.
The present study investigates the in vivo response to this scaffold in a critical-sized defect in a rabbit knee. Results shows the scaffolds ability to guide the host reparative response leading to tissue regeneration with a zonal organisation, repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark.
The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation.
Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems.
Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence.
In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated.
In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context.
This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone osteocytes, osteoclasts and osteoblasts , which was representative of the bone's capacity to sense microdamage and subsequently initiate a basic multicellular unit response.
Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate.
We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis.
Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis.
Substrate composition and dimensionality direct osteocyte gene expression. Bone tissue engineering is a promising strategy to enhance bone regeneration and scaffolds are increasingly used as delivery platforms for therapeutics to direct bone formation by mesenchymal stromal cells MSCs in vivo.
Additionally, the role of mechanotransduction in osteoinduction as well as the age-dependent loss of differentiation potential in MSCs is now well recognised.
However, there is limited information about age-dependent effects in MSCs mechanosensitivity and the genes controlling these effects.
Therefore, this project aims to identify age-dependent mechanoresponsive targets in order to functionalize scaffolds for the induction of enhanced bone formation.
These results not only show an enhanced propensity for osteogenic differentiation of C-MSCs compared to A-MSCs induced by the surface properties, but also the activation of angiogenic pathways i.
Future investigations into the age-dependent mechanisms underpinning the mechanoresponsiveness of MSCs may thus elucidate new therapeutic targets for improved bone and vascular regeneration.
Scaffolds provide a framework for construct development; therefore, it is crucial to identify the optimal pore size for augmented tissue formation.
Consequently, primary mesenchymal stem cells MSCs were assessed and their behaviour compared to osteoblasts. MSCs responded similarly to osteoblasts whereby cell attachment and scaffold infiltration improved with increasing pore size.
However, MSCs showed reduced cell motility, proliferation, and scaffold infiltration compared to osteoblasts. In summary, these results reveal how larger pores promote improved cell infiltration, essential for construct development, however the optimal scaffold pore size can be cell type specific.
As such, this study highlights a necessity to tailor both scaffold micro-architecture and cell-type when designing constructs for successful bone tissue engineering applications.
Defects within bones caused by trauma and other pathological complications may often require the use of a range of therapeutics to facilitate tissue regeneration.
A number of approaches have been widely utilized for the delivery of such therapeutics via physical encapsulation or chemical immobilization suggesting significant promise in the healing of bone defects.
The study focuses on the chemical immobilization of osteostatin, a pentapeptide of the parathyroid hormone PTHrP , within a collagen-hydroxyapatite scaffold.
In vitro characterization demonstrates that this cross-linking method of immobilization supports a pro-osteogenic effect on osteoblasts.
Collectively, this study suggests that such an approach of chemical immobilization offers greater spatiotemporal control over growth factors and can significantly modulate tissue regeneration.
Such a system may be adopted for a range of different proteins and thus offers the potential for the treatment of various complex pathologies that require localized mediation of drug delivery.
Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic properties, and induces a contractile phenotype in smooth muscle cells.
Spatiotemporal delivery of small molecule therapeutics using a thermosensitive liposome loaded hydrogel. The pre-vascularisation of a collagen-chondroitin sulphate scaffold using human amniotic fluid-derived stem cells to enhance and stabilise endothelial cell-mediated vessel formation.
A major problem in tissue engineering TE is graft failure in vivo due to core degradation in in vitro engineered constructs designed to regenerate thick tissues such as bone.
The integration of constructs post-implantation relies on the rapid formation of functional vasculature. A recent approach to overcome core degradation focuses on the creation of cell-based, pre-engineered vasculature formed within the TE construct in vitro, prior to implantation in vivo.
The primary objective of this study was to investigate whether an amniotic fluid-derived stem cell AFSC - human umbilical vein endothelial cell HUVEC co-culture could be used to engineer in vitro vasculature in a collagen chondroitin sulphate CCS scaffold.
However, this microcapillary-like structure formation was reduced in hypoxic conditions. Overall, however, these results demonstrate the potential of this newly developed co-culture system for the formation of pre-engineered vasculature within TE constructs.
Published by Elsevier Ltd. Incorporation of fibrin into a collagen-glycosaminoglycan matrix results in a scaffold with improved mechanical properties and enhanced capacity to resist cell-mediated contraction.
Fibrin has many uses as a tissue engineering scaffold, however many in vivo studies have shown a reduction in function resulting from the susceptibility of fibrin to cell-mediated contraction.
The overall aim of the present study was to develop and characterise a reinforced natural scaffold using fibrin, collagen and glycosaminoglycan FCG , and to examine the cell-mediated contraction of this scaffold in comparison to fibrin gels.
Through the use of an injection loading technique, a homogenous FCG scaffold was developed. Mechanical testing showed a six-fold increase in compressive modulus and a thirty-fold increase in tensile modulus of fibrin when reinforced with a collagen-glycosaminoglycan backbone structure.
Human vascular smooth muscle cells vSMCs were successfully incorporated into the FCG scaffold and demonstrated excellent viability over 7 days, while proliferation of these cells also increased significantly.
The FCG scaffold, which is composed of natural biomaterials, shows potential for use in applications where dimensional stability is crucial to the functionality of the tissue.
The use of collagen-based scaffolds to simulate prostate cancer bone metastases with potential for evaluating delivery of nanoparticulate gene therapeutics.
Life in 3D is Never Flat: The development of safe, effective and patient-acceptable drug products is an expensive and lengthy process and the risk of failure at different stages of the development life-cycle is high.
Improved biopharmaceutical tools which are robust, easy to use and accurately predict the in vivo response are urgently required to help address these issues.
In this review the advantages and challenges of in vitro 3D versus 2D cell culture models will be discussed in terms of evaluating new drug products at the pre-clinical development stage.
Examples of models with a 3D architecture including scaffolds, cell-derived matrices, multicellular spheroids and biochips will be described.
The ability to simulate the microenvironment of tumours and vital organs including the liver, kidney, heart and intestine which have major impact on drug absorption, distribution, metabolism and toxicity will be evaluated.
Examples of the application of 3D models including a role in formulation development, pharmacokinetic profiling and toxicity testing will be critically assessed.
Although utilisation of 3D cell culture models in the field of drug delivery is still in its infancy, the area is attracting high levels of interest and is likely to become a significant in vitro tool to assist in drug product development thus reducing the requirement for unnecessary animal studies.
Published by Elsevier B. Incorporation of the natural marine multi-mineral dietary supplement Aquamin enhances osteogenesis and improves the mechanical properties of a collagen-based bone graft substitute.
Aquamin is a commercially-available supplement derived from the algae species Lithothamnion, which has proven osteogenic potential. By harnessing this potential and combining Aquamin with a collagen scaffold, with architecture and composition optimised for bone repair, the aim of this study was to develop a natural osteo-stimulative bone graft substitute.
The fabrication process produced a homogenous Aquamin distribution throughout the scaffold. Release kinetics revealed that in the first 12 h, the entire Aquamin content was released from the F however, less than half of Aquamin in the F was released with the remainder released approximately 21 days later giving an initial burst release followed by a delayed release.
Osteoblasts cultured on the CollAqua scaffolds showed improved osteogenesis as measured by alkaline phosphatase, osteopontin and osteocalcin expression.
This was confirmed by increased mineralisation as determined by von Kossa and Alizarin red staining. In conclusion, a cell and growth factor free collagen-based bone graft substitute with enhanced mechanical properties has been developed.
The addition of Aquamin to the collagen biomaterial significantly improved mineralisation by osteoblasts and results in a new product which may be capable of enhancing osteogenesis to facilitate bone repair in vivo.
When such engineered tissues are implanted in vivo they have been shown to induce bone formation by recapitulating aspects of the developmental process of endochondral ossification.
Alginate, a naturally sourced and biocompatible hydrogel, offers an attractive 3D environment to facilitate the in vitro chondrogenesis of MSCs.
Furthermore, such alginate hydrogels can potentially be used to engineer cartilage tissues of scale to promote endochondral bone regeneration in large bone defects.
The aim of this study was to investigate the ability of chondrogenically-primed MSC-laden alginate hydrogels to induce healing in two distinct critically-sized defect models.
However, any newly deposited bone was generated appositional to the alginate material, and occurred only superficially or where the alginate was seen to degrade.
Alginate material was found to persist within both orthotopic locations 8 weeks post-implantation, with its slow rate of degradation appearing to prevent complete bone regeneration.
In conclusion, while chondrogenically primed MSC—alginate constructs can act as templates to treat critically-sized defects within bones formed through either intramembranous or endochondral ossification, further optimization of the degradation kinetics of the hydrogel itself will be required to accelerate bone tissue deposition and facilitate complete regeneration of such defects.
In-situ structural characterisation of 2D nanomaterials incorporated into bioengineered materials. Jun Microscience Microscopy Congress. Platelet-rich plasma releasate differently stimulates cellular commitment toward the chondrogenic lineage according to concentration.
Platelet-rich plasma has been used to treat articular cartilage defects, with the expectations of anabolic and anti-inflammatory effects.
However, its role on cellular chondrogenic or fibrogenic commitment is still a controversy. Herein, the role of platelet-rich plasma releasate, the product obtained following platelet-rich plasma activation, on cellular commitment toward the chondrogenic lineage was evaluated in vitro.
Human nasoseptal chondrogenic cells and human bone marrow mesenchymal stromal cells were used as cell types already committed to the chondrogenic lineage and undifferentiated cells, respectively, as different concentrations of platelet-rich plasma releasate were tested in comparison to commonly used fetal bovine serum.
Low concentration of platelet-rich plasma releasate 2. In a three-dimensional culture system, platelet-rich plasma releasate alone did not induce full nasoseptal chondrogenic cells cartilage-like pellet formation.
Nonetheless, platelet-rich plasma releasate played a significant role on cell commitment as high-passage nasoseptal chondrogenic cells only originated cartilage-like pellets when expanded in the presence of platelet-rich plasma releasate rather than fetal bovine serum.
Histological analyses and measurements of pellet area demonstrated that even low concentrations of platelet-rich plasma releasate were enough to prevent nasoseptal chondrogenic cells from losing their chondrogenic potential due to in vitro expansion thereby promoting their recommitment.
Low concentration of platelet-rich plasma releasate supplemented in chondrogenic medium also increased the chondrogenic potential of mesenchymal stromal cells seeded on collagen-hyaluronic acid scaffolds, as observed by an increase in chondrogenic-related gene expression, sulfated glycosaminoglycan production, and compressive modulus following in vitro culture.
In conclusion, platelet-rich plasma releasate was able to prevent cellular chondrogenic capacity loss, inducing regain of their phenotype, and modulate cell commitment.
Our data support the hypothesis of platelet-rich plasma chondrogenic. Given a lovely ride by Paddy, he really flew his hurdles and seems to be improving nicely.
It is great to see him winning now as he has always looked like a good horse at home, but for some reason he wasn't reproducing it on the track.
The penny has finally dropped this season, this is his third win from his last four runs and his confidence is high. Queen Of Mantua ran well to finish a close third, but Are They Your Own was a bit disappointing, he made a mistake at the first hurdle, and then could never get into a position to challenge and dropped away through the field.
We are going to Bangor today with Potters Dream in the 3 mile conditional jockeys handicap hurdle, Conor rides him today and we hope he can step up a bit on his previous form, this is his first run for us.
Off to Wolverhampton now with Abbraccio on the all weather over 1m5f, then a quick shuttle up to Uttoxeter for Gud Day and Henrio.
We have had some heavy showers, but it isn't really getting into the ground at home. A busy day with three runner. Gud Day is having his first run over fences so fingers crossed and Henrio is having his first run for us so again hopefully he'll run a nice race and give us something to build on.
You know things are getting busy when you have to get Jelly to dust her saddle of!! Well Mett looked after her very well.
We had a lot of rain last night so hopefully the ground has eased a bit, also it would be great to use our grass gallop again.
It's amazing what a difference the weather has made to all of the horses, this time last year they were coming in from the field looking lean and be-draggled due to the constant cold and wet summer we had, but now they look big and strong.
Let's hope it is reflected in their races! Abbraccio is running over 1m5f, Gud Day is running in his first chase and Henrio is having his first run for us in a bumper.
A great win by Dark Energy at Market Rasen, he really loves it there! What was most pleasing was how he stuck his neck out and battled to win after the last fence, he never used to do that.
Me And Ben ran a cracker to come a fast finishing second, she should be winning soon. Noble Bacchus got no further than the first hurdle as he jinked a bit to his right and Alain fell off!
At least he redeemed himself slightly Alain not the horse by winning on Dark Energy. Today we are o Beggars Velvet was found to be not quite right last time out, and we think he is better over fences anyway.
Officially Modern is having his second run over fences and will hopefully get the trip a bit better as we felt he didn't quite get home last time, he is a very gassy horse who boiled over before the race last time at Worcester, so we will try to get him to the start a bit calmer today.
Me and Ben ran another blinder at Cartmel to finish close second. Well done Lois who looks after all of today's runners! Sections of this page.
Email or Phone Password Forgot account? I'm a big fan Best of luck See More. Information about Page Insights Data. This is worth watching - our very own Conor really struggles with mornings, "friend" Harry Beswick came up with a novel idea!!!!
Fergal O'Brien Racing Blog. The morning after the night before - here is a review of a great Saturday for the yard A Great Day Yesterday. What a great day we had yesterday with an across the card treble, Alvarado won the staying chase at Cheltenham in good style, jumping and travelling well all the way and bursting clear after the last.
This was a good performance in what was described as the most competitive renewal of this race.
obrien fergal -Ich, der Urheber dieses Werkes, veröffentliche es unter der folgenden Lizenz:. This means that free usage outside of Wikimedia projects under the following terms of licence is possible: The timestamp is only as accurate as the clock in the camera, and it may be completely wrong. Auf diesem Niveau konnte er sich dann auch stabilisieren. Auch wenn er dazu nicht verpflichtet ist, kann der Uploader dir eventuell dabei helfen, solche Nachweise einzuholen. The following page uses this file: Sonst kam er aber auch bei den anderen Turnieren nicht über die dritte Runde hinaus. Ein Modelvertrag oder ein anderer Nachweis einer solchen Zustimmung kann dich vor rechtlichen Schwierigkeiten schützen. The following page uses this file: This means that free usage outside of Wikimedia projects under the following terms of licence is possible: Ich würde mich sehr über die Zusendung eines Belegexemplares bzw. The following page uses this file: Deshalb musste er durch zahlreiche Qualifikationsrunden, aber schon bei seinem ersten Turnier, dem Dubai Classic , erreichte er die Runde der Letzten Ebdon war im Jahr darauf gleich viermal sein Gegner. Auch wenn er dazu nicht verpflichtet ist, kann der Uploader dir eventuell dabei helfen, solche Nachweise einzuholen. Ich, der Urheber dieses Werkes, veröffentliche es unter der folgenden Lizenz:. Bitte schreiben Sie eine E-Mail an derhexer wikipedia. Sonst kam er aber auch bei den anderen Turnieren nicht über die dritte Runde hinaus. Dort war dann allerdings erneut gegen McManus mit 7: I, the copyright holder of this work, hereby publish it under the following license:. Snookerspieler Irland Ire Geboren Mann. Deshalb musste er durch zahlreiche Qualifikationsrunden, aber schon bei seinem ersten Turnier, dem Dubai Classic , erreichte er die Runde der Letzten Seit ist er Profi auf der Snooker Main Tour. Inhalte nur unter Verwendung von Lizenzbedingungen weitergeben, die mit denen dieses Lizenzvertrages identisch, vergleichbar oder kompatibel sind.
Another winner to add to our tally yesterday at Sedgefield. Today we have 2 runners at Wetherby.
A crisp morning on the gallops. Some cracking shots thanks to Dr Simon. We are working the horses this morning which is always exciting to watch.
The weather is holding us back a little bit but we are making the most of the quicker ground with some summer horses we have kept in.
He was given a super ride by Alain who hit him into contention coming into the home straight and this exciting young horse wanted to win.
A very busy Saturday morning with a huge turnout at the yard. The weather was very cold but everyone wrapped up warm and braved it out.
We enjoyed a solid day yesterday. Hopefully something will come to light or maybe the trip was a bit too…. A busy morning at the yard with preparations on full steam ahead for the first Cheltenham meeting of the season.
Oscar Rose gained a very well deserved win yesterday in the Mares Novice hurdle at Worcester. This biography of a living person needs additional citations for verification.
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December Learn how and when to remove this template message. Retrieved 16 January Retrieved 25 February Fergal O'Brien wins longest frame in snooker history to qualify".
Paul Hunter Classic Ranking  [nb 1]. Riga Masters [nb 3]. World Open [nb 4]. Paul Hunter Classic [nb 5]. European Masters [nb 6].