Physical forces,such as magnetic and mechanical stimulation,are known to play a significant role in the regulation of cell response.In the present study,a biomimetic regeneration patch was fabricated using E-jet 3 D p...Physical forces,such as magnetic and mechanical stimulation,are known to play a significant role in the regulation of cell response.In the present study,a biomimetic regeneration patch was fabricated using E-jet 3 D printing,which integrates mechanical and magnetic stimulation in a biocompatible"one-pot reaction"strategy when combined with a static magnetic field(SMF).The magneto-based therapeutic regeneration patch induced myoblasts to form aligned and multinucleated myotubes,regulated the expression of myogenic-related genes,and activated the p38αmitogen-activated protein kinase pathway via the initiation of myogenic differentiation.To validate the efficiency of the proposed strategy,the regeneration patch was implanted into mice and exposed to a suitable SMF,which resulted in significantly enhanced in vivo skeletal muscle regeneration.The findings demonstrated that appropriate external physical stimulation provides a suitable biophysical microenvironment that is conducive to tissue regeneration.The method used in the present study represents a promising technique to induce the regeneration of damaged skeletal muscle tis sue.展开更多
Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics.Although the efficiencies of vaccines are limited,they can be enhanced by a well-designed antigen delivery sy...Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics.Although the efficiencies of vaccines are limited,they can be enhanced by a well-designed antigen delivery system that promotes sufficient antigen presentation of dendritic cells(DCs)for initiating high T cell immunity.Herein,antigen-loaded manganese oxide(Mn_(3)O_(4))triangular-shaped ultrasmall nanoparti-cles were prepared to stimulate DC-based immunotherapy under the guidance of T_(1)magnetic resonance imaging.The FDA-approved triblock copolymer Pluronic^(■)F-68 wasused not onlyto transferthe phase from hydrophobic to hydrophilic but also to enrich antigen loading and improve the biocompatibility of the prepared nanoparticles.Ovalbumin(OVA),a model antigen,was adsorbed on the surface of polymer-coated nanoparticles through electrostatic interaction to form Mn_(3)O_(4)@PF68-OVA nanoparticle-antigen complexes to stimulate DC-based immunization and antigen-specific T cell immunity.The Mn_(3)O_(4)@PF68-OVA nanovaccine(NV)induces negligible toxicity effects against 4T1 and bone marrow-derived dendritic cells(BMDCs)by conventional methods supports the proliferation of intestine organoids,which are an innovative three-dimensional cytotoxicity evaluation system,thereby indicating their potential safety for in vivo cancer therapies.The designed paramagnetic nanovaccine possessed excellent OVA delivery to dendritic-regulated antigen-specific T cells in vitro by stimulating the maturation level of BMDCs.In ad-dition,Mn_(3)O_(4)@PF68-OVA NVs enhance immunity in vivo by increasing the T-cells and M1 macrophages,which suggests improved immunity.Excitingly,vaccination with Mn_(3)O_(4)@PF68-OVA offer complete pro-tection in the prophylactic group and significant tumor inhibition in the therapeutic group against B16-OVA tumor.In addition,the designed nanovaccine demonstrated high T_(1)-MR imaging in the tumor,fur-ther justifying enhanced tumor accumulation and capability to real-time monitor the treatment proce-dure.This study presents a promising nanosystem to design an effective nanovaccine for T_(1)-MR imaging-guided tumor immunotherapy.展开更多
In order to provide a biomimetic natural extracellular matrix microenvironment with excellent mechanical capacity for tissue regeneration,a novel porous hybrid glycidyl methacrylate-modified silk fibroin/poly(L-lactic...In order to provide a biomimetic natural extracellular matrix microenvironment with excellent mechanical capacity for tissue regeneration,a novel porous hybrid glycidyl methacrylate-modified silk fibroin/poly(L-lactic acid-co-ε-caprolactone)–polyethylene glycol diacrylate(SFMA/P(LLA-CL)–PEGDA)hybrid three-dimensional(3D)nanofibrous scaffolds was successfully fabricated through the combination of 3D nanofibrous platforms and divinyl PEGDA based photocrosslinking,and then further improved water resistance by ethanol vapor post-treatment.Scanning electron microscopy and micro-computed tomography results demonstrated significant PEGDA hydrogel-like matrices bonded nanofibers,which formed a 3D structure similar to that of“steel bar(nanofibers)‒cement(PEGDA)”,with proper pore size,high porosity,and high pore connectivity density.Meanwhile,the hybrid 3D nanofibrous scaffolds showed outstanding swelling properties as well as improved compressive and tensile properties.Furthermore,these hybrid 3D nanofibrous scaffolds could provide a biocompatible microenvironment,capable of inducing the material‒cell hybrid and regulating human umbilical vein endothelial cells proliferation.They thus present significant potential in tissue regeneration.展开更多
Herein,the rational design micromilieus involved silk fibroin(SF)-based materials have been used to encapsulate the osteoblasts,forming an extracellular coated shell on the cells,which exhibited the high potential to ...Herein,the rational design micromilieus involved silk fibroin(SF)-based materials have been used to encapsulate the osteoblasts,forming an extracellular coated shell on the cells,which exhibited the high potential to shift the regulation of osteoblasts to osteocytes by encapsulation cues.SF coating treated cells showed a change in cell morphology from osteoblasts-like to osteocytes-like shape comparedwith untreated ones.Moreover,the expression of alkaline phosphatase(ALP),collagen I(Col I)and osteocalcin(OcN)further indicated a potential approach for inducingosteoblasts regulation,which typically accelerates calcium deposition and cell calcification,presenting a key role for the SF encapsulation in controlling osteoblasts behavior.This discovery showed that SF-based cell encapsulation could be used for osteoblasts behavior regulation,which offers a great potential to modulate mammalian cells'phenotype involvingalternatingsurrounding cues.展开更多
基金financially supported by the Natural Science Foundation of Hunan Province(No.2019JJ40018)Hunan University(No.53112102)。
文摘Physical forces,such as magnetic and mechanical stimulation,are known to play a significant role in the regulation of cell response.In the present study,a biomimetic regeneration patch was fabricated using E-jet 3 D printing,which integrates mechanical and magnetic stimulation in a biocompatible"one-pot reaction"strategy when combined with a static magnetic field(SMF).The magneto-based therapeutic regeneration patch induced myoblasts to form aligned and multinucleated myotubes,regulated the expression of myogenic-related genes,and activated the p38αmitogen-activated protein kinase pathway via the initiation of myogenic differentiation.To validate the efficiency of the proposed strategy,the regeneration patch was implanted into mice and exposed to a suitable SMF,which resulted in significantly enhanced in vivo skeletal muscle regeneration.The findings demonstrated that appropriate external physical stimulation provides a suitable biophysical microenvironment that is conducive to tissue regeneration.The method used in the present study represents a promising technique to induce the regeneration of damaged skeletal muscle tis sue.
基金financially supported by the National Natural Science Foundation of China(No.51672250 and 51902289)the Zhejiang International Science and Technology Cooperation Project(Nos.2021C01180 and 2019C04020)the Research Foundation of ZSTU(No.18012134-Y).
文摘Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics.Although the efficiencies of vaccines are limited,they can be enhanced by a well-designed antigen delivery system that promotes sufficient antigen presentation of dendritic cells(DCs)for initiating high T cell immunity.Herein,antigen-loaded manganese oxide(Mn_(3)O_(4))triangular-shaped ultrasmall nanoparti-cles were prepared to stimulate DC-based immunotherapy under the guidance of T_(1)magnetic resonance imaging.The FDA-approved triblock copolymer Pluronic^(■)F-68 wasused not onlyto transferthe phase from hydrophobic to hydrophilic but also to enrich antigen loading and improve the biocompatibility of the prepared nanoparticles.Ovalbumin(OVA),a model antigen,was adsorbed on the surface of polymer-coated nanoparticles through electrostatic interaction to form Mn_(3)O_(4)@PF68-OVA nanoparticle-antigen complexes to stimulate DC-based immunization and antigen-specific T cell immunity.The Mn_(3)O_(4)@PF68-OVA nanovaccine(NV)induces negligible toxicity effects against 4T1 and bone marrow-derived dendritic cells(BMDCs)by conventional methods supports the proliferation of intestine organoids,which are an innovative three-dimensional cytotoxicity evaluation system,thereby indicating their potential safety for in vivo cancer therapies.The designed paramagnetic nanovaccine possessed excellent OVA delivery to dendritic-regulated antigen-specific T cells in vitro by stimulating the maturation level of BMDCs.In ad-dition,Mn_(3)O_(4)@PF68-OVA NVs enhance immunity in vivo by increasing the T-cells and M1 macrophages,which suggests improved immunity.Excitingly,vaccination with Mn_(3)O_(4)@PF68-OVA offer complete pro-tection in the prophylactic group and significant tumor inhibition in the therapeutic group against B16-OVA tumor.In addition,the designed nanovaccine demonstrated high T_(1)-MR imaging in the tumor,fur-ther justifying enhanced tumor accumulation and capability to real-time monitor the treatment proce-dure.This study presents a promising nanosystem to design an effective nanovaccine for T_(1)-MR imaging-guided tumor immunotherapy.
基金This work was sponsored by the Jiaxing Public Welfare Research Project(Grant Nos.2021AY10062 and 2021AY10063)the Zhejiang Provincial Natural Science Foundation of China(Grant Nos.LY20C100003 and LY22C100001)the National Undergraduate Training Program for Innovation and Entrepreneurship(Grant No.202010354009).
文摘In order to provide a biomimetic natural extracellular matrix microenvironment with excellent mechanical capacity for tissue regeneration,a novel porous hybrid glycidyl methacrylate-modified silk fibroin/poly(L-lactic acid-co-ε-caprolactone)–polyethylene glycol diacrylate(SFMA/P(LLA-CL)–PEGDA)hybrid three-dimensional(3D)nanofibrous scaffolds was successfully fabricated through the combination of 3D nanofibrous platforms and divinyl PEGDA based photocrosslinking,and then further improved water resistance by ethanol vapor post-treatment.Scanning electron microscopy and micro-computed tomography results demonstrated significant PEGDA hydrogel-like matrices bonded nanofibers,which formed a 3D structure similar to that of“steel bar(nanofibers)‒cement(PEGDA)”,with proper pore size,high porosity,and high pore connectivity density.Meanwhile,the hybrid 3D nanofibrous scaffolds showed outstanding swelling properties as well as improved compressive and tensile properties.Furthermore,these hybrid 3D nanofibrous scaffolds could provide a biocompatible microenvironment,capable of inducing the material‒cell hybrid and regulating human umbilical vein endothelial cells proliferation.They thus present significant potential in tissue regeneration.
基金supported by the National Natural Science Foundation of China(Grant Nos.51902289 and 51672250)the Natural Science Foundation of Zhejiang Province(Grant No.LQ19E020010)+2 种基金the Project of Zhejiang Provincial Department of Education(Grant No.Y201840323)the Key Project of Zhejiang Science and Technology(Grant Nos.2021C01180 and 2019C04020)the Research Foundation of ZSTU(Grant Nos.18012134-Y and 2020Q008).
文摘Herein,the rational design micromilieus involved silk fibroin(SF)-based materials have been used to encapsulate the osteoblasts,forming an extracellular coated shell on the cells,which exhibited the high potential to shift the regulation of osteoblasts to osteocytes by encapsulation cues.SF coating treated cells showed a change in cell morphology from osteoblasts-like to osteocytes-like shape comparedwith untreated ones.Moreover,the expression of alkaline phosphatase(ALP),collagen I(Col I)and osteocalcin(OcN)further indicated a potential approach for inducingosteoblasts regulation,which typically accelerates calcium deposition and cell calcification,presenting a key role for the SF encapsulation in controlling osteoblasts behavior.This discovery showed that SF-based cell encapsulation could be used for osteoblasts behavior regulation,which offers a great potential to modulate mammalian cells'phenotype involvingalternatingsurrounding cues.