Fabrication Of Anisotropic Magnetic Hydrogel And Its Application As 3D Tumor Cell Culture Substrate

The research problems of biomedical engineering are often complex because of the specialty of interdisciplinary.Materials with simple structures and monofunction are often unable to meet the needs of researchs.And researchers also found that composite materials combining of materials with different properties have new structures or features.Based on these aspects,multifunctional composite material is a research hot spot of biomedical engineering.As one of the branches of nano-materials,magnetic nanomaterial draws sustained attention because of its good biocompatibility and responses to external magnetic field.Composites based on magnetic nanomaterials shows a rapid development in recent years.Hydrogel,due to its excellent characteristics,is widely used as components of composites.Materials with different characteristics composited together will not only maintain their original characteristics,but also create new structures and functions with the assistance of applied functional field.In this paper,a series of novel magnetic hydrogels with anisotropic structures and properties were developed by combining magnetic field assisted assembly and gelation.The interrelation of anisotropic structures and characteristic were studied and the application of these composite materials in tumor diagnosis and treatment was preliminarily explored.The specific content of the paper includes the following sections:1.A novel magnetic hydrogel was prepared via static magnetic induced assembly of magnetic nanomaterials and gelation of hydrogel.The preparation strategy was simple and feasible,having excellent versatility.The basic demands of magnetic nanomaterials and hydrogel for fabricating of anisotropic magnetic hydrogel were explored based on computer simulation and calculation.The effects of the type,size and concentration of magnetic nanomaterials,the concentration of hydrogel monomer and cross-linker,the magnetic field strength and the assembled time on the structures of magnetic hydrogel were studied.And it is firstly reported that the high resolution Micro CT was used for the first time to characterize and reconstruction the distribution of magnetic nanomaterial assemblies in 3D.2.The mechanical,optical,magnetic properties and hyperemia under alternating magnetic field were studied.The mechanical property of magnetic hydrogel was anisotropic and the enhancement of magnetic nanomaterial assemblies was changed with the direction.The distribution of these assemblies endowed the composite materials optical properties of a 3D raster.The controllable enhancement effect of magnetic hydrogel in alternating magnetic field was firstly discovered and reported.And the hyperthermia mechanism was studied and the results showed that anisotropic hyperemia property might be caused by the magnetic interaction between assembled magnetic nanomaterials.It was showed that the adjustable thermogenesis can be applied in the controlled drug release of magnetic hydrogels.Due to the controllability of thermogenesis,the aligned magnetic hydrogel will have promising potentials in the clinic applications.3.The anisotropic magnetic hydrogels prepared with assistance of alternating magnetic field/rotating magnetic field were firstly reported.The effect of alternating magnetic field/rotating magnetic field on the assemblies’ structures was preliminarily explored.Results showed that the assistance of alternating magnetic field could improve the magnetic interaction between assembled magnetic nanomaterials;the rotating magnetic field would induce magnetic nanomaterial to form disk like structures.Magnetic hydrogel with containing these structures also showed anisotropic hyperthermia properties and increase of rotating speed of magnetic field will improve the magnetothermal effect.4.By combining anti cell-adhesive hydrogel and cell-adhesive magnetic colloidal assemblies together,magnetic hydrogels were fabricated and sliced.This composite material provided a matrix with cell-adhesive microarray on the surface.Cells from different cell lines could spontaneously form multicellular spheroids when cultured on this functionalized interface.This may be due to the balance of cell-matrix interaction and cell-cell interaction induced by the interfacial properties.Furthermore,cells which could only form loose cell aggregates in classic 3D cell culture model(such as hanging drop system)were able to be promoted to form compact multicellular spheroids on this platform.Cells cultured on sliced magnetic hydrogels showed higher drug resistance than those cultured on plates.In the light of its simplicity in fabricating as well as effectiveness in promoting formation of multicellular spheroids which mimic solid tumor or tissue in vivo,this composite material holds promise in anti-cancer drugs or hyperthermia therapies evaluation in vitro in the future.