Adequate drug delivery across the blood–brain barrier(BBB) is a critical factor in treating central nervous system(CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is t...Adequate drug delivery across the blood–brain barrier(BBB) is a critical factor in treating central nervous system(CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization,the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2(LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine(PLL)and negatively charged surface of fibers;this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.展开更多
Living cells and active factors are the two core elements of tissue repair,directly affecting the healing efficiency of damaged tissue.Nanofat(NF)can release living cells,such as adipose-derived stem cells(ADSCs),as w...Living cells and active factors are the two core elements of tissue repair,directly affecting the healing efficiency of damaged tissue.Nanofat(NF)can release living cells,such as adipose-derived stem cells(ADSCs),as well as active growth factors to promote angiogenesis,thus realizing cell-based wound healing.Herein,a novel living electrospun short fibrous sponge is constructed by modifying three-dimensional(3D)bionic short fibers with engineered NF.The uniform distribution of the polydopamine(PDA)modification endows the living sponges with stable mechanical properties,reversible water absorption and excellent adhesion even after repeated compression by an external force and long-term aqueous immersion.Meanwhile,the living electrospun short fibrous sponges with uniform NF modification contain living cells such as ADSCs and active growth factors such as vascular endothelial growth factor(VEGF),which can effectively promote the tube formation of human umbilical vein endothelial cells(HUVECs).In vivo,the living sponges can effectively and continuously act on wounds and act as a bionic living skin to prevent the loss of internal nutrients,creating a comfortable and favorable microenvironment for tissue regeneration and promoting the healing of diabetic wounds.Therefore,living electrospun short fibrous sponges via engineered NF are expected to achieve continuous wound healing with in situ living cells and active factors in injured tissues.展开更多
基金supported by the National Key Research and Development Program of China (2020YFA0908200)the National Natural Science Foundation of China (82271204, 81771138, and32000937)+1 种基金the Shanghai Municipal Health Commission(20204Y0354)Sanming Project of Medicine in Shenzhen(SZSM202211007)。
文摘Adequate drug delivery across the blood–brain barrier(BBB) is a critical factor in treating central nervous system(CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization,the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2(LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine(PLL)and negatively charged surface of fibers;this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.
基金funded by the National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China General Program(32000937 and 51873107)+3 种基金Shanghai Municipal Health Commission(20204Y0354)Youth Innovation Technology Project of Higher School in Shandong Province(20190919)China Postdoctoral Science Foundation(2022T150426)Program of Shanghai Academic Research Leader(22XD1422600).
文摘Living cells and active factors are the two core elements of tissue repair,directly affecting the healing efficiency of damaged tissue.Nanofat(NF)can release living cells,such as adipose-derived stem cells(ADSCs),as well as active growth factors to promote angiogenesis,thus realizing cell-based wound healing.Herein,a novel living electrospun short fibrous sponge is constructed by modifying three-dimensional(3D)bionic short fibers with engineered NF.The uniform distribution of the polydopamine(PDA)modification endows the living sponges with stable mechanical properties,reversible water absorption and excellent adhesion even after repeated compression by an external force and long-term aqueous immersion.Meanwhile,the living electrospun short fibrous sponges with uniform NF modification contain living cells such as ADSCs and active growth factors such as vascular endothelial growth factor(VEGF),which can effectively promote the tube formation of human umbilical vein endothelial cells(HUVECs).In vivo,the living sponges can effectively and continuously act on wounds and act as a bionic living skin to prevent the loss of internal nutrients,creating a comfortable and favorable microenvironment for tissue regeneration and promoting the healing of diabetic wounds.Therefore,living electrospun short fibrous sponges via engineered NF are expected to achieve continuous wound healing with in situ living cells and active factors in injured tissues.