Bioreactors are used to dynamically condition engineered tissues to achieve the required degree of maturation before in vivo implantation.Integrating sensors and imaging capabilities into bioreactors can help us under...Bioreactors are used to dynamically condition engineered tissues to achieve the required degree of maturation before in vivo implantation.Integrating sensors and imaging capabilities into bioreactors can help us understand how the culture environment influences tissue maturation and growth.Additionally,this enables the monitoring of tissue constructs and provides critical information for quality control.This study aimed to develop a standardized,self-contained,uniaxial bioreactor module for the clinical manufacturing of tissue constructs;this system would benefit from unidirectional mechanical or electrical stimulation,or both.We achieved this goal by integrating stimulation and sensing components that provide an optimal culture environment and monitoring capabilities to improve tissue manufacturing.The uniaxial bioreactor module included integrated,user-friendly mechanical and electrical stimulations with force measurement to enhance the preconditioning of the engineered tissues.Also,a sensor loop and media exchange system were integrated to monitor the culture environment and cellular metabolites over time,and the camera system above the tissue construct enabled the macroscopic visualization of tissue maturation.Furthermore,the onboard media exchange system was programmed into the module to maintain aseptic culture conditions in the long term.Subsequently,using native skeletal muscle tissue and tissue-engineered skeletal muscle constructs,the performance of the uniaxial bioreactor module was validated for its application in preconditioning and enhancing tissue maturation.展开更多
There is an unprecedented need for new treatments for renal failure,as the incidence of this disease is increasing disproportionately to advancements in therapies.Current treatments are limited by the availability of ...There is an unprecedented need for new treatments for renal failure,as the incidence of this disease is increasing disproportionately to advancements in therapies.Current treatments are limited by the availability of viable organs,for which there is a worldwide lack.These treatment modalities also require a substantial amount of infrastructure,significantly limiting the access to care in most countries.Kidney tissue engineering approaches promise to develop alternative solutions that address many of the inadequacies in current care.Although many advancements have been made—primarily in the past decade—in biofabrication and whole-organ tissue engineering,many challenges remain.One major hindrance to the progress of current tissue engineering approaches is establishing successful vascularization of developed engineered tissue constructs.This review focuses on the recent advancements that address the vascular challenge,including the biofabrication of vasculature,whole-organ engineering through decellularization and recellularization approaches,microscale organogenesis,and vascularization using organoids in the context of kidney tissue engineering.We also highlight the specific challenges that remain in developing successful strategies capable of clinical translation.展开更多
The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore,maintain or improve tissue function following disease or injury.To maximize the biological function of a tissue-engin...The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore,maintain or improve tissue function following disease or injury.To maximize the biological function of a tissue-engineered clinical product,specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for implantation.Specifically,the bioreactor should be designed to mimic the mechanical,electrochemical and biochemical environment that the product will be exposed to in vivo.Real-time monitoring of the functional capacity of tissue-engineered products during manufacturing is a critical component of the quality management process.The present review provides a brief overview of bioreactor engineering considerations.In addition,strategies for bioreactor automation,in-line product monitoring and quality assurance are discussed.展开更多
In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candidates were on the waiting list by the end of the year. Despite advances in renal transplant immunology, approximately 40...In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candidates were on the waiting list by the end of the year. Despite advances in renal transplant immunology, approximately 40% of recipients will die or lose graft within 10 years. The limitations of current therapies for renal failure have led researchers to explore the development of modalities that could improve, restore, or replace the renal function. The aim of this paper is to describe a reasonable approach for kidney regeneration and review the current literature regarding cell sources and mechanisms to develop a bioengineering kidney. Due to kidneys peculiar anatomy, extracellular matrix based scaffolds are rational starting point for their regeneration. The perfusion of detergents through the kidney vasculature is an effcient method for delivering decel-lularizing agents to cells and for removing of cellular material from the tissue. Many efforts have focused on the search of a reliable cell source to provide enrichment for achieving stable renal cell systems. For an effcient bioengineered kidney, these cells must be attached to the organ and then maturated into the bio-ractors, which simulates the human body environment.A functional bioengineered kidney is still a big challenge for scientists. In the last ten years we have got many improvements on the feld of solid organ regeneration; however, we are still far away from the main target. Currently, regenerative centers worldwide have been striving to find feasible strategies to develop bioengi-neered kidneys. Cell-scaffold technology gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis or immunosupression. The potential of bioengi-neered organ is to provide a reliable source of organs, which can be refunctionalized and transplanted.展开更多
Burns are a significant cause of trauma,and over the years,the focus of patient care has shifted from just survival to facilitation of improved functional outcomes.Typically,burn treatment,especially in the case of ex...Burns are a significant cause of trauma,and over the years,the focus of patient care has shifted from just survival to facilitation of improved functional outcomes.Typically,burn treatment,especially in the case of extensive burn injuries,involves surgical excision of injured skin and reconstruction of the burn injury with the aid of skin substitutes.Conventional skin substitutes do not contain all skin cell types and do not facilitate recapitulation of native skin physiology.Three-dimensional(3D)bioprinting for reconstruction of burn injuries involves layer-by-layer deposition of cells along with scaffolding materials over the injured areas.Skin bioprinting can be done either in situ or in vitro.Both these approaches are similar except for the site of printing and tissue maturation.There are technological and regulatory challenges that need to be overcome for clinical translation of bioprinted skin for burn reconstruction.However,the use of bioprinting for skin reconstruction following burns is promising;bioprinting will enable accurate placement of cell types and precise and reproducible fabrication of constructs to replace the injured or damaged sites.Overall,3D bioprinting is a very transformative technology,and its use for wound reconstruction will lead to a paradigm shift in patient outcomes.In this review,we aim to introduce bioprinting,the different stages involved,in vitro and in vivo skin bioprinting,and the various clinical and regulatory challenges in adoption of this technology.展开更多
Marrow niches in osteosarcoma(OS)are a specialized microenvironment that is essential for the maintenance and regulation of OS cells.However,existing animal xenograft models are plagued by variability,complexity,and h...Marrow niches in osteosarcoma(OS)are a specialized microenvironment that is essential for the maintenance and regulation of OS cells.However,existing animal xenograft models are plagued by variability,complexity,and high cost.Herein,we used a decellularized osteosarcoma extracellular matrix(dOsEM)loaded with extracellular vesicles from human bone marrow-derived stem cells(hBMSC-EVs)and OS cells as a bioink to construct a micro-osteosarcoma(micro-OS)through 3D printing.The micro-OS was further combined with a microfluidic system to develop into an OS-on-a-chip(OOC)with a built-in recirculating perfusion system.The OOC system successfully integrated bone marrow niches,cell‒cell and cell-matrix crosstalk,and circulation,allowing a more accurate representation of OS characteristics in vivo.Moreover,the OOC system may serve as a valuable research platform for studying OS biological mechanisms compared with traditional xenograft models and is expected to enable precise and rapid evaluation and consequently more effective and comprehensive treatments for OS.展开更多
基金possible by the US Army Medical Research and Development Command through the Medical Technology Enterprise Consortium under Contract#W81XWH-15-9-0001.
文摘Bioreactors are used to dynamically condition engineered tissues to achieve the required degree of maturation before in vivo implantation.Integrating sensors and imaging capabilities into bioreactors can help us understand how the culture environment influences tissue maturation and growth.Additionally,this enables the monitoring of tissue constructs and provides critical information for quality control.This study aimed to develop a standardized,self-contained,uniaxial bioreactor module for the clinical manufacturing of tissue constructs;this system would benefit from unidirectional mechanical or electrical stimulation,or both.We achieved this goal by integrating stimulation and sensing components that provide an optimal culture environment and monitoring capabilities to improve tissue manufacturing.The uniaxial bioreactor module included integrated,user-friendly mechanical and electrical stimulations with force measurement to enhance the preconditioning of the engineered tissues.Also,a sensor loop and media exchange system were integrated to monitor the culture environment and cellular metabolites over time,and the camera system above the tissue construct enabled the macroscopic visualization of tissue maturation.Furthermore,the onboard media exchange system was programmed into the module to maintain aseptic culture conditions in the long term.Subsequently,using native skeletal muscle tissue and tissue-engineered skeletal muscle constructs,the performance of the uniaxial bioreactor module was validated for its application in preconditioning and enhancing tissue maturation.
文摘There is an unprecedented need for new treatments for renal failure,as the incidence of this disease is increasing disproportionately to advancements in therapies.Current treatments are limited by the availability of viable organs,for which there is a worldwide lack.These treatment modalities also require a substantial amount of infrastructure,significantly limiting the access to care in most countries.Kidney tissue engineering approaches promise to develop alternative solutions that address many of the inadequacies in current care.Although many advancements have been made—primarily in the past decade—in biofabrication and whole-organ tissue engineering,many challenges remain.One major hindrance to the progress of current tissue engineering approaches is establishing successful vascularization of developed engineered tissue constructs.This review focuses on the recent advancements that address the vascular challenge,including the biofabrication of vasculature,whole-organ engineering through decellularization and recellularization approaches,microscale organogenesis,and vascularization using organoids in the context of kidney tissue engineering.We also highlight the specific challenges that remain in developing successful strategies capable of clinical translation.
基金US Army Medical Research and Development Command through the Medical Technology Enterprise Consortium under Contract#W81XWH-15-9-0001.
文摘The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore,maintain or improve tissue function following disease or injury.To maximize the biological function of a tissue-engineered clinical product,specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for implantation.Specifically,the bioreactor should be designed to mimic the mechanical,electrochemical and biochemical environment that the product will be exposed to in vivo.Real-time monitoring of the functional capacity of tissue-engineered products during manufacturing is a critical component of the quality management process.The present review provides a brief overview of bioreactor engineering considerations.In addition,strategies for bioreactor automation,in-line product monitoring and quality assurance are discussed.
文摘In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candidates were on the waiting list by the end of the year. Despite advances in renal transplant immunology, approximately 40% of recipients will die or lose graft within 10 years. The limitations of current therapies for renal failure have led researchers to explore the development of modalities that could improve, restore, or replace the renal function. The aim of this paper is to describe a reasonable approach for kidney regeneration and review the current literature regarding cell sources and mechanisms to develop a bioengineering kidney. Due to kidneys peculiar anatomy, extracellular matrix based scaffolds are rational starting point for their regeneration. The perfusion of detergents through the kidney vasculature is an effcient method for delivering decel-lularizing agents to cells and for removing of cellular material from the tissue. Many efforts have focused on the search of a reliable cell source to provide enrichment for achieving stable renal cell systems. For an effcient bioengineered kidney, these cells must be attached to the organ and then maturated into the bio-ractors, which simulates the human body environment.A functional bioengineered kidney is still a big challenge for scientists. In the last ten years we have got many improvements on the feld of solid organ regeneration; however, we are still far away from the main target. Currently, regenerative centers worldwide have been striving to find feasible strategies to develop bioengi-neered kidneys. Cell-scaffold technology gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis or immunosupression. The potential of bioengi-neered organ is to provide a reliable source of organs, which can be refunctionalized and transplanted.
文摘Burns are a significant cause of trauma,and over the years,the focus of patient care has shifted from just survival to facilitation of improved functional outcomes.Typically,burn treatment,especially in the case of extensive burn injuries,involves surgical excision of injured skin and reconstruction of the burn injury with the aid of skin substitutes.Conventional skin substitutes do not contain all skin cell types and do not facilitate recapitulation of native skin physiology.Three-dimensional(3D)bioprinting for reconstruction of burn injuries involves layer-by-layer deposition of cells along with scaffolding materials over the injured areas.Skin bioprinting can be done either in situ or in vitro.Both these approaches are similar except for the site of printing and tissue maturation.There are technological and regulatory challenges that need to be overcome for clinical translation of bioprinted skin for burn reconstruction.However,the use of bioprinting for skin reconstruction following burns is promising;bioprinting will enable accurate placement of cell types and precise and reproducible fabrication of constructs to replace the injured or damaged sites.Overall,3D bioprinting is a very transformative technology,and its use for wound reconstruction will lead to a paradigm shift in patient outcomes.In this review,we aim to introduce bioprinting,the different stages involved,in vitro and in vivo skin bioprinting,and the various clinical and regulatory challenges in adoption of this technology.
基金the Shanghai Pujiang Program(21PJ1409200)the China Postdoctoral Science Foundation(2022M722122)+6 种基金Three-year Action Plan of Shenkang Development Center(SHDC2020CR2019B)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiao Tong University School of Medicine(2022LHB07,2022LHA01)Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal Systemthe Fundamental Research Funds for the Central Universities(YG2023LC07)Clinical Research Program of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYLJ202122)the Project of Biobank from Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(YBKB202116)the National Scientific Foundation of China(82171993,81972058,82130073).
文摘Marrow niches in osteosarcoma(OS)are a specialized microenvironment that is essential for the maintenance and regulation of OS cells.However,existing animal xenograft models are plagued by variability,complexity,and high cost.Herein,we used a decellularized osteosarcoma extracellular matrix(dOsEM)loaded with extracellular vesicles from human bone marrow-derived stem cells(hBMSC-EVs)and OS cells as a bioink to construct a micro-osteosarcoma(micro-OS)through 3D printing.The micro-OS was further combined with a microfluidic system to develop into an OS-on-a-chip(OOC)with a built-in recirculating perfusion system.The OOC system successfully integrated bone marrow niches,cell‒cell and cell-matrix crosstalk,and circulation,allowing a more accurate representation of OS characteristics in vivo.Moreover,the OOC system may serve as a valuable research platform for studying OS biological mechanisms compared with traditional xenograft models and is expected to enable precise and rapid evaluation and consequently more effective and comprehensive treatments for OS.
