Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function.First,this review provides a brief int...Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function.First,this review provides a brief introduction to the current state-of-the-art for neuroectoderm brain organoid development,emphasizing their biggest advantages in comparison with classical two-dimensional cell cultures and animal models.However,despite their usefulness for developmental studies,a major limitation for most brain organoid models is the absence of contributing cell types from endodermal and mesodermal origin.As such,current research is highly investing towards the incorporation of a functional vasculature and the microglial immune component.In this review,we will specifically focus on the development of immune-competent brain organoids.By summarizing the different approaches applied to incorporate microglia,it is highlighted that immune-competent brain organoids are not only important for studying neuronal network formation,but also offer a clear future as a new tool to study inflammatory responses in vitro in 3D in a brainlike environment.Therefore,our main focus here is to provide a comprehensive overview of assays to measure microglial phenotype and function within brain organoids,with an outlook on how these findings could better understand neuronal network development or restoration,as well as the influence of physical stress on microglia-containing brain organoids.Finally,we would like to stress that even though the development of immune-competent brain organoids has largely evolved over the past decade,their full potential as a pre-clinical tool to study novel therapeutic approaches to halt or reduce inflammation-mediated neurodegeneration still needs to be explored and validated.展开更多
As we navigate the transition from the Fourth to the Fifth Industrial Revolution,the emerging fields of biomanufacturing and biofabrication are transforming life sciences and healthcare.These sectors are benefiting fr...As we navigate the transition from the Fourth to the Fifth Industrial Revolution,the emerging fields of biomanufacturing and biofabrication are transforming life sciences and healthcare.These sectors are benefiting from a synergy of synthetic and engineering biology,sustainable manufacturing,and integrated design principles.Advanced techniques such as 3D bioprinting,tissue engineering,directed assembly,and self-assembly are instrumental in creating biomimetic scaffolds,tissues,organoids,medical devices,and biohybrid systems.The field of biofabrication in the United Kingdom and Ireland is emerging as a pivotal force in bioscience and healthcare,propelled by cutting-edge research and development.Concentrating on the production of biologically functional products for use in drug delivery,in vitro models,and tissue engineering,research institutions across these regions are dedicated to innovating healthcare solutions that adhere to ethical standards while prioritising sustainability,affordability,and healthcare system benefits.展开更多
Treatment of acute ischaemic stroke(AIS)focuses on rapid recanalisation of the occluded artery.In recent years,advent of mechanical thrombectomy devices and new procedures have accelerated the analysis of thrombi retr...Treatment of acute ischaemic stroke(AIS)focuses on rapid recanalisation of the occluded artery.In recent years,advent of mechanical thrombectomy devices and new procedures have accelerated the analysis of thrombi retrieved during the endovascular thrombectomy procedure.Despite ongoing developments and progress in AIS imaging techniques,it is not yet possible to conclude definitively regarding thrombus characteristics that could advise on the probable efficacy of thrombolysis or thrombectomy in advance of treatment.Intraprocedural devices with dignostic capabilities or new clinical imaging approaches are needed for better treatment of AIS patients.In this review,what is known about the composition of the thrombi that cause strokes and the evidence that thrombus composition has an impact on success of acute stroke treatment has been examined.This review also discusses the evidence that AIS thrombus composition varies with aetiology,questioning if suspected aetiology could be a useful indicator to stroke physicians to help decide the best acute course of treatment.Furthermore,this review discusses the evidence that current widely used radiological imaging tools can predict thrombus composition.Further use of new emerging technologies based on bioimpedance,as imaging modalities for diagnosing AIS and new medical device tools for detecting thrombus composition in situ has been introduced.Whether bioimpedance would be beneficial for gaining new insights into in situ thrombus composition that could guide choice of optimum treatment approach is also reviewed.展开更多
Due to the nature of non-invasive wound closure,the ability to close different forms of leaks,and the potential to immobilize various devices,bioadhesives are altering clinical practices.As one of the vital factors,bi...Due to the nature of non-invasive wound closure,the ability to close different forms of leaks,and the potential to immobilize various devices,bioadhesives are altering clinical practices.As one of the vital factors,bioadhesives’strength is determined by adhesion and cohesion mechanisms.As well as being essential for adhesion strength,the cohesion mechanism also influences their bulk functions and the way the adhesives can be applied.Although there are many published reports on various adhesion mechanisms,cohesion mechanisms have rarely been addressed.In this review,we have summarized the most used cohesion mechanisms.Furthermore,the relationship of cohesion strategies and adhesion strategies has been discussed,including employing the same functional groups harnessed for adhesion,using combinational approaches,and exploiting different strategies for cohesion mechanism.By providing a comprehensive insight into cohesion strategies,the paper has been integrated to offer a roadmap to facilitate the commercialization of bioadhesives.展开更多
The depletion of chondroitin sulfates(CSs)within the intervertebral disc(IVD)during degenerative disc disease(DDD)results in a decrease in tissue hydration,a loss of fluid movement,cell apoptosis,a loss of nerve growt...The depletion of chondroitin sulfates(CSs)within the intervertebral disc(IVD)during degenerative disc disease(DDD)results in a decrease in tissue hydration,a loss of fluid movement,cell apoptosis,a loss of nerve growth inhibition and ultimately,the loss of disc function.To date,little is known with regards to the structure and content of chondroitin sulfates(CSs)during IVD ageing.The behavior of glycosaminoglycans(GAGs),specifically CSs,as well as xylosyltransferase I(XT-I)and glucuronyltransferase I(GT-I),two key enzymes involved in CS synthesis as a primer of glycosaminoglycan(GAG)chain elongation and GAG synthesis in the nucleus pulposus(NP),respectively,were evaluated in a bovine ageing IVD model.Here,we showed significant changes in the composition of GAGs during the disc ageing process(6-month-old,2-year-old and 8-year-old IVDs representing the immature to mature skeleton).The CS quantity and composition of annulus fibrosus(AF)and NP were determined.The expression of both XT-I and GT-I was detected using immunohistochemistry.A significant decrease in GAGs was observed during the ageing process.CSs are affected at both the structural and quantitative levels with important changes in sulfation observed upon maturity,which correlated with a decrease in the expression of both XT-I and GT-I.A progressive switch of the sulfation profile was noted in both NP and AF tissues from 6 months to 8 years.These changes give an appreciation of the potential impact of CSs on the disc biology and the development of therapeutic approaches for disc regeneration and repair.展开更多
Rapid and efficient tendon fixation to a bone following trauma or in response to degenerative processes can be facilitated using a tendon anchoring device.Osteomimetic biomaterials,and in particular,bio-resorbable pol...Rapid and efficient tendon fixation to a bone following trauma or in response to degenerative processes can be facilitated using a tendon anchoring device.Osteomimetic biomaterials,and in particular,bio-resorbable polymer composites designed to match the mineral phase content of native bone,have been shown to exhibit osteoinductive and osteoconductive properties in vivo and have been used in bone fixation for the past 2 decades.In this study,a resorbable,bioactive,and mechanically robust citrate-based composite formulated from poly(octamethylene citrate)(POC)and hydroxyapatite(HA)(POC-HA)was investigated as a potential tendon-fixation biomaterial.In vitro analysis with human Mesenchymal Stem Cells(hMSCs)indicated that POC-HA composite materials supported cell adhesion,growth,and proliferation and increased calcium deposition,alkaline phosphatase production,the expression of osteogenic specific genes,and activation of canonical pathways leading to osteoinduction and osteoconduction.Further,in vivo evaluation of a POC-HA tendon fixation device in a sheep metaphyseal model indicates the regenerative and remodeling potential of this citrate-based composite material.Together,this study presents a comprehensive in vitro and in vivo analysis of the functional response to a citrate-derived composite tendon anchor and indicates that citrate-based HA composites offer improved mechanical and osteogenic properties relative to commonly used resorbable tendon anchor devices formulated from poly(L-co-D,l-lactic acid)and tricalcium phosphate PLDLA-TCP.展开更多
Glutaraldehyde(Glut)is an extensively used sterilant and fixative for the crosslinking of natural soft tissue biomaterials like bovine pericardium(BP)to provide stability and is required for its application in vivo.Th...Glutaraldehyde(Glut)is an extensively used sterilant and fixative for the crosslinking of natural soft tissue biomaterials like bovine pericardium(BP)to provide stability and is required for its application in vivo.There is plenty of debate around the reaction mechanism of Glut with natural biomaterials.Differential scanning calorimetry(DSC)is a commonly used technique that is typically used to measure the thermal profile of polymers.However,a variation known as quasi-isothermal modulated differential scanning calorimetry(QiMDSC)has been utilised for the analysis of polymorphic transformations in both the pharmaceutical and food industries.This communication will address QiMDSC as a method for analysing soft tissue biomaterials and their crosslinking mechanisms and how it can be applied to other biomaterial applications.展开更多
基金funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant agreement No.813263(PMSMat Train,granted to UF,PP,MV,and DP)provided by the Fund for Scientific Research Flanders(FWO-Vlaanderen)of the Flemish Government(FWO sabbatical bench fee K800224N granted to PP)and ERA-NET Re Park(granted to PP)。
文摘Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function.First,this review provides a brief introduction to the current state-of-the-art for neuroectoderm brain organoid development,emphasizing their biggest advantages in comparison with classical two-dimensional cell cultures and animal models.However,despite their usefulness for developmental studies,a major limitation for most brain organoid models is the absence of contributing cell types from endodermal and mesodermal origin.As such,current research is highly investing towards the incorporation of a functional vasculature and the microglial immune component.In this review,we will specifically focus on the development of immune-competent brain organoids.By summarizing the different approaches applied to incorporate microglia,it is highlighted that immune-competent brain organoids are not only important for studying neuronal network formation,but also offer a clear future as a new tool to study inflammatory responses in vitro in 3D in a brainlike environment.Therefore,our main focus here is to provide a comprehensive overview of assays to measure microglial phenotype and function within brain organoids,with an outlook on how these findings could better understand neuronal network development or restoration,as well as the influence of physical stress on microglia-containing brain organoids.Finally,we would like to stress that even though the development of immune-competent brain organoids has largely evolved over the past decade,their full potential as a pre-clinical tool to study novel therapeutic approaches to halt or reduce inflammation-mediated neurodegeneration still needs to be explored and validated.
基金supported by the W.D.Armstrong Trust.YYSH is funded by the European Research Council(ERC-St G,758865)the UK Research and Innovations(UKRI)Biotechnology and Biological Sciences Research Council(BB/W014564/1)+9 种基金funding from a UKRI Future Leaders Fellowship(MR/V024965/1)supported by the BBSRC London Interdisciplinary Doctoral(LIDo)Programmethe funding support of EPSRC(EP/W004860/1,EP/X033686/1)and MRC(MR/V029827/1,MR/W030381/1)the European Research Council(Pro Li Cell,772462)for supportthe NIHR Nottingham Biomedical Research Centre,University of Nottingham,Nottingham,UK and the AO Foundation,AO CMF(AOCMF-21-04S)funding support from grant MR/W01470X/1the EPSRC(EP/W018977/1)for financial supportfunding from the EPSRC(EP/T020792/1)funding from Biomat DB+(Horizon Europe 101058779)funding received from Science Foundation Ireland(SFI)—Grant No.13/RC/2073_P2。
文摘As we navigate the transition from the Fourth to the Fifth Industrial Revolution,the emerging fields of biomanufacturing and biofabrication are transforming life sciences and healthcare.These sectors are benefiting from a synergy of synthetic and engineering biology,sustainable manufacturing,and integrated design principles.Advanced techniques such as 3D bioprinting,tissue engineering,directed assembly,and self-assembly are instrumental in creating biomimetic scaffolds,tissues,organoids,medical devices,and biohybrid systems.The field of biofabrication in the United Kingdom and Ireland is emerging as a pivotal force in bioscience and healthcare,propelled by cutting-edge research and development.Concentrating on the production of biologically functional products for use in drug delivery,in vitro models,and tissue engineering,research institutions across these regions are dedicated to innovating healthcare solutions that adhere to ethical standards while prioritising sustainability,affordability,and healthcare system benefits.
基金funded by European Regional Development Fund(13/RC/2073_2)Sensome(No grant number),Science Foundation Ireland(13/RC/2073_2).
文摘Treatment of acute ischaemic stroke(AIS)focuses on rapid recanalisation of the occluded artery.In recent years,advent of mechanical thrombectomy devices and new procedures have accelerated the analysis of thrombi retrieved during the endovascular thrombectomy procedure.Despite ongoing developments and progress in AIS imaging techniques,it is not yet possible to conclude definitively regarding thrombus characteristics that could advise on the probable efficacy of thrombolysis or thrombectomy in advance of treatment.Intraprocedural devices with dignostic capabilities or new clinical imaging approaches are needed for better treatment of AIS patients.In this review,what is known about the composition of the thrombi that cause strokes and the evidence that thrombus composition has an impact on success of acute stroke treatment has been examined.This review also discusses the evidence that AIS thrombus composition varies with aetiology,questioning if suspected aetiology could be a useful indicator to stroke physicians to help decide the best acute course of treatment.Furthermore,this review discusses the evidence that current widely used radiological imaging tools can predict thrombus composition.Further use of new emerging technologies based on bioimpedance,as imaging modalities for diagnosing AIS and new medical device tools for detecting thrombus composition in situ has been introduced.Whether bioimpedance would be beneficial for gaining new insights into in situ thrombus composition that could guide choice of optimum treatment approach is also reviewed.
基金The authors would like to acknowledge the Science Foundation Ireland(SFI)and the European Regional Development Fund(Grant Number 13/RC/2073_P2)for financial assistanceYB is supported by funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 713690.
文摘Due to the nature of non-invasive wound closure,the ability to close different forms of leaks,and the potential to immobilize various devices,bioadhesives are altering clinical practices.As one of the vital factors,bioadhesives’strength is determined by adhesion and cohesion mechanisms.As well as being essential for adhesion strength,the cohesion mechanism also influences their bulk functions and the way the adhesives can be applied.Although there are many published reports on various adhesion mechanisms,cohesion mechanisms have rarely been addressed.In this review,we have summarized the most used cohesion mechanisms.Furthermore,the relationship of cohesion strategies and adhesion strategies has been discussed,including employing the same functional groups harnessed for adhesion,using combinational approaches,and exploiting different strategies for cohesion mechanism.By providing a comprehensive insight into cohesion strategies,the paper has been integrated to offer a roadmap to facilitate the commercialization of bioadhesives.
基金This publication has emanated from research conducted with the financial support of Science Foundation Ireland(SFI)cofunded under the European Regional Development Fund under Grant Number 13/RC/2073.
文摘The depletion of chondroitin sulfates(CSs)within the intervertebral disc(IVD)during degenerative disc disease(DDD)results in a decrease in tissue hydration,a loss of fluid movement,cell apoptosis,a loss of nerve growth inhibition and ultimately,the loss of disc function.To date,little is known with regards to the structure and content of chondroitin sulfates(CSs)during IVD ageing.The behavior of glycosaminoglycans(GAGs),specifically CSs,as well as xylosyltransferase I(XT-I)and glucuronyltransferase I(GT-I),two key enzymes involved in CS synthesis as a primer of glycosaminoglycan(GAG)chain elongation and GAG synthesis in the nucleus pulposus(NP),respectively,were evaluated in a bovine ageing IVD model.Here,we showed significant changes in the composition of GAGs during the disc ageing process(6-month-old,2-year-old and 8-year-old IVDs representing the immature to mature skeleton).The CS quantity and composition of annulus fibrosus(AF)and NP were determined.The expression of both XT-I and GT-I was detected using immunohistochemistry.A significant decrease in GAGs was observed during the ageing process.CSs are affected at both the structural and quantitative levels with important changes in sulfation observed upon maturity,which correlated with a decrease in the expression of both XT-I and GT-I.A progressive switch of the sulfation profile was noted in both NP and AF tissues from 6 months to 8 years.These changes give an appreciation of the potential impact of CSs on the disc biology and the development of therapeutic approaches for disc regeneration and repair.
基金Foundation Ireland(SFI)and the European Regional Development Fund(Grant No.13/RC/2073).
文摘Rapid and efficient tendon fixation to a bone following trauma or in response to degenerative processes can be facilitated using a tendon anchoring device.Osteomimetic biomaterials,and in particular,bio-resorbable polymer composites designed to match the mineral phase content of native bone,have been shown to exhibit osteoinductive and osteoconductive properties in vivo and have been used in bone fixation for the past 2 decades.In this study,a resorbable,bioactive,and mechanically robust citrate-based composite formulated from poly(octamethylene citrate)(POC)and hydroxyapatite(HA)(POC-HA)was investigated as a potential tendon-fixation biomaterial.In vitro analysis with human Mesenchymal Stem Cells(hMSCs)indicated that POC-HA composite materials supported cell adhesion,growth,and proliferation and increased calcium deposition,alkaline phosphatase production,the expression of osteogenic specific genes,and activation of canonical pathways leading to osteoinduction and osteoconduction.Further,in vivo evaluation of a POC-HA tendon fixation device in a sheep metaphyseal model indicates the regenerative and remodeling potential of this citrate-based composite material.Together,this study presents a comprehensive in vitro and in vivo analysis of the functional response to a citrate-derived composite tendon anchor and indicates that citrate-based HA composites offer improved mechanical and osteogenic properties relative to commonly used resorbable tendon anchor devices formulated from poly(L-co-D,l-lactic acid)and tricalcium phosphate PLDLA-TCP.
基金supported by both Boston Scientific Galway[grant number:Higher Education].
文摘Glutaraldehyde(Glut)is an extensively used sterilant and fixative for the crosslinking of natural soft tissue biomaterials like bovine pericardium(BP)to provide stability and is required for its application in vivo.There is plenty of debate around the reaction mechanism of Glut with natural biomaterials.Differential scanning calorimetry(DSC)is a commonly used technique that is typically used to measure the thermal profile of polymers.However,a variation known as quasi-isothermal modulated differential scanning calorimetry(QiMDSC)has been utilised for the analysis of polymorphic transformations in both the pharmaceutical and food industries.This communication will address QiMDSC as a method for analysing soft tissue biomaterials and their crosslinking mechanisms and how it can be applied to other biomaterial applications.
