Animal models have been extensively used as a gold standard in various biological research,including immu-nological studies.Despite high availability and ease of handling procedure,they inadequately represent complex ...Animal models have been extensively used as a gold standard in various biological research,including immu-nological studies.Despite high availability and ease of handling procedure,they inadequately represent complex interactions and unique cellular properties in humans due to inter-species genetic and microenvironmental differences which have resulted in clinical-stage failures.Organoid technology has gained enormous attention as they provide sophisticated insights about tissue architecture and functionality in miniaturized organs.In this review,we describe the use of organoid system to overcome limitations in animal-based investigations,such as physiological mismatch with humans,costly,time-consuming,and low throughput screening.Immune organoids are one of the specific advancements in organogenesis ex vivo,which can reflect human adaptive immunity with more physiologically relevant aspects.We discuss how immune organoids are established from patient-derived lymphoid tissues,as well as their characteristics and functional features to understand immune mechanisms and responses.Also,some bioengineering perspectives are considered for any potential progress of immuno-engineered organoids.展开更多
Bone marrow-derived mesenchymal stem cell(MSC)is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties.Conventional cell expansion methods using 2D tissue cultur...Bone marrow-derived mesenchymal stem cell(MSC)is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties.Conventional cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers,but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected in vivo.To overcome these challenges,in this work,we describe a 3D dynamic hydrogel using magneto-stimulation for direct MSC manufacturing to therapy.With our technology,we found that dynamic mechanical stimulation(DMS)enhanced matrix-integrinβ1 interactions which induced MSCs spreading and proliferation.In addition,DMS could modulate MSC biofunctions including directing MSC differentiation into specific lineages and boosting paracrine activities(e.g.,growth factor secretion)through YAP nuclear localization and FAK-ERK pathway.With our magnetic hydrogel,complex procedures from MSC manufacturing to final clinical use,can be integrated into one single platform,and we believe this‘all-in-one’technology could offer a paradigm shift to existing standards in MSC therapy.展开更多
Microbial resistance to current antibiotics therapies is a major cause of implant failure and adverse clinical outcomes in orthopaedic surgery.Recent developments in advanced antimicrobial nanotechnologies provide num...Microbial resistance to current antibiotics therapies is a major cause of implant failure and adverse clinical outcomes in orthopaedic surgery.Recent developments in advanced antimicrobial nanotechnologies provide numerous opportunities to effective remove resistant bacteria and prevent resistance from occurring through unique mechanisms.With tunable physicochemical properties,nanomaterials can be designed to be bactericidal,antifouling,immunomodulating,and capable of delivering antibacterial compounds to the infection region with spatiotemporal accuracy.Despite its substantial advancement,an important,but under-explored area,is potential microbial resistance to nanomaterials and how this can impact the clinical use of antimicrobial nanotechnologies.This review aims to provide a better understanding of nanomaterial-associated microbial resistance to accelerate bench-to-bedside translations of emerging nanotechnologies for effective control of implant associated infections.展开更多
基金supported by the NUS Presidential Young Professor-ship,Ministry of Education Tier 1,National Medical Research Council Open Fund Young Investigator Research Grant,Manufacturing,Trade and Connectivity Young Investigator Research Grant,iHT OOE award,NUS Healthy Longevity TRP Aged Mice Funding,Joint NCIS Centre Grant and NUS Centre for Cancer Research(N2CR)Seed Funding Programme,TREX Grant,PCM Seed Grant,and PREPARE Strategic Open Grant Call(Vaccines&Therapeutics Co-Operative Programme).
文摘Animal models have been extensively used as a gold standard in various biological research,including immu-nological studies.Despite high availability and ease of handling procedure,they inadequately represent complex interactions and unique cellular properties in humans due to inter-species genetic and microenvironmental differences which have resulted in clinical-stage failures.Organoid technology has gained enormous attention as they provide sophisticated insights about tissue architecture and functionality in miniaturized organs.In this review,we describe the use of organoid system to overcome limitations in animal-based investigations,such as physiological mismatch with humans,costly,time-consuming,and low throughput screening.Immune organoids are one of the specific advancements in organogenesis ex vivo,which can reflect human adaptive immunity with more physiologically relevant aspects.We discuss how immune organoids are established from patient-derived lymphoid tissues,as well as their characteristics and functional features to understand immune mechanisms and responses.Also,some bioengineering perspectives are considered for any potential progress of immuno-engineered organoids.
基金supported by NUS Presidential Young Professorship,MOE Tier 1 grantsupported by the NUS Research Scholarship.
文摘Bone marrow-derived mesenchymal stem cell(MSC)is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties.Conventional cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers,but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected in vivo.To overcome these challenges,in this work,we describe a 3D dynamic hydrogel using magneto-stimulation for direct MSC manufacturing to therapy.With our technology,we found that dynamic mechanical stimulation(DMS)enhanced matrix-integrinβ1 interactions which induced MSCs spreading and proliferation.In addition,DMS could modulate MSC biofunctions including directing MSC differentiation into specific lineages and boosting paracrine activities(e.g.,growth factor secretion)through YAP nuclear localization and FAK-ERK pathway.With our magnetic hydrogel,complex procedures from MSC manufacturing to final clinical use,can be integrated into one single platform,and we believe this‘all-in-one’technology could offer a paradigm shift to existing standards in MSC therapy.
基金funding support from the NUS Presidential Young Professorship and NUS Technological Innovations in Infectious Diseases Translational Research.
文摘Microbial resistance to current antibiotics therapies is a major cause of implant failure and adverse clinical outcomes in orthopaedic surgery.Recent developments in advanced antimicrobial nanotechnologies provide numerous opportunities to effective remove resistant bacteria and prevent resistance from occurring through unique mechanisms.With tunable physicochemical properties,nanomaterials can be designed to be bactericidal,antifouling,immunomodulating,and capable of delivering antibacterial compounds to the infection region with spatiotemporal accuracy.Despite its substantial advancement,an important,but under-explored area,is potential microbial resistance to nanomaterials and how this can impact the clinical use of antimicrobial nanotechnologies.This review aims to provide a better understanding of nanomaterial-associated microbial resistance to accelerate bench-to-bedside translations of emerging nanotechnologies for effective control of implant associated infections.
