Tendon/ligament-to-bone healing poses a formidable clinical challenge due to the complex structure,composition,cell population and mechanics of the interface.With rapid advances in tissue engineering,a variety of stra...Tendon/ligament-to-bone healing poses a formidable clinical challenge due to the complex structure,composition,cell population and mechanics of the interface.With rapid advances in tissue engineering,a variety of strategies including advanced biomaterials,bioactive growth factors and multiple stem cell lineages have been developed to facilitate the healing of this tissue interface.Given the important role of structure-function relationship,the review begins with a brief description of enthesis structure and composition.Next,the biomimetic biomaterials including decellularized extracellular matrix scaffolds and synthetic-/natural-origin scaffolds are critically examined.Then,the key roles of the combination,concentration and location of various growth factors in biomimetic application are emphasized.After that,the various stem cell sources and culture systems are described.At last,we discuss unmet needs and existing challenges in the ideal strategies for tendon/ligament-to-bone regeneration and highlight emerging strategies in the field.展开更多
Although ultra-small nanoclusters(USNCs,<2 nm)have immense application capabilities in biomedicine,the investigation on body-wide organ responses towards USNCs is scant.Here,applying a novel strategy of single-cell...Although ultra-small nanoclusters(USNCs,<2 nm)have immense application capabilities in biomedicine,the investigation on body-wide organ responses towards USNCs is scant.Here,applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues,we systematically evaluate the interactions between the host and calcium phosphate(CaP)USNCs at the organism level.Combining single-cell mass cytometry,and magnetic luminex assay results,we identify dynamic immune responses to CaP USNCs at the single cell resolution.The innate immune is initially activated and followed by adaptive immune activation,as evidenced by dynamic immune cells proportions.Furthermore,using Nano Genome Atlas of multi-tissues,we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney.Moreover,based on the immunological response profiles,histological evaluation of major organs and local tissue,and a body-wide transcriptomics,we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection.Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.展开更多
基金supported by the National Key Research and Development Program of China(2018YFC1105100)NSFC grants(81871764,82072463,81772418,81972099)Zhejiang Provincial Natural Science Foundation of China(LR20H060001).
文摘Tendon/ligament-to-bone healing poses a formidable clinical challenge due to the complex structure,composition,cell population and mechanics of the interface.With rapid advances in tissue engineering,a variety of strategies including advanced biomaterials,bioactive growth factors and multiple stem cell lineages have been developed to facilitate the healing of this tissue interface.Given the important role of structure-function relationship,the review begins with a brief description of enthesis structure and composition.Next,the biomimetic biomaterials including decellularized extracellular matrix scaffolds and synthetic-/natural-origin scaffolds are critically examined.Then,the key roles of the combination,concentration and location of various growth factors in biomimetic application are emphasized.After that,the various stem cell sources and culture systems are described.At last,we discuss unmet needs and existing challenges in the ideal strategies for tendon/ligament-to-bone regeneration and highlight emerging strategies in the field.
基金the National Key Research and Development Program of China(2018YFC1105100)NSFC grants(T2121004,81972099,82072463,81871764)+1 种基金Zhejiang Provincial Natural Science Foundation of China(LZ22H060002,LR20H060001)Fundamental Research Funds for the Central Universities.
文摘Although ultra-small nanoclusters(USNCs,<2 nm)have immense application capabilities in biomedicine,the investigation on body-wide organ responses towards USNCs is scant.Here,applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues,we systematically evaluate the interactions between the host and calcium phosphate(CaP)USNCs at the organism level.Combining single-cell mass cytometry,and magnetic luminex assay results,we identify dynamic immune responses to CaP USNCs at the single cell resolution.The innate immune is initially activated and followed by adaptive immune activation,as evidenced by dynamic immune cells proportions.Furthermore,using Nano Genome Atlas of multi-tissues,we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney.Moreover,based on the immunological response profiles,histological evaluation of major organs and local tissue,and a body-wide transcriptomics,we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection.Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.
