3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper researches.Herein,by mixing biodegradable polylactic acid(P...3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper researches.Herein,by mixing biodegradable polylactic acid(PLA)nanofibers in the modified alginate with different concentrations of Ca^(2+),we significantly enhance the stiffness range of microgels while retaining the pore size,which provides bionic microenvironment for tumor analysis.As a proof of concept,we simulated the mechanical characteristics of breast tumors by encapsulating cells in 3D microgels with diverse stiffness,and analyzed cellular behaviors of two typical breast cancer cell lines:MCF-7 and SUM-159.Results showed that with the addition of 2.0%(w/v)PLA short nanofibers,the Young’s modulus of modified alginate increased more than three-fold.Besides preserving high survival and proliferation rates,both cells also displayed stronger migration ability in soft microgel spheres,where RT-qPCR analysis revealed the underlying changes at the genetic level.This systematic study demonstrated our method is powerful for creating widely adjustable 3D mechanical microenvironment,and the results of cellular behavior analysis shows its promising application prospects in tumorigenesis and progression.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22034005,81973569,and 21621003).
文摘3D microgels with various mechanical properties have been important platforms tumor metastasis analysis,and widely adjustable stiffness is crucial for deeper researches.Herein,by mixing biodegradable polylactic acid(PLA)nanofibers in the modified alginate with different concentrations of Ca^(2+),we significantly enhance the stiffness range of microgels while retaining the pore size,which provides bionic microenvironment for tumor analysis.As a proof of concept,we simulated the mechanical characteristics of breast tumors by encapsulating cells in 3D microgels with diverse stiffness,and analyzed cellular behaviors of two typical breast cancer cell lines:MCF-7 and SUM-159.Results showed that with the addition of 2.0%(w/v)PLA short nanofibers,the Young’s modulus of modified alginate increased more than three-fold.Besides preserving high survival and proliferation rates,both cells also displayed stronger migration ability in soft microgel spheres,where RT-qPCR analysis revealed the underlying changes at the genetic level.This systematic study demonstrated our method is powerful for creating widely adjustable 3D mechanical microenvironment,and the results of cellular behavior analysis shows its promising application prospects in tumorigenesis and progression.
