Development Of Electrohydrodynamic Printing For 3D Micron/nano Scaled Medicines

Fibrous matirces with well-ordered three-dimensional(3D)structures containing various functional matrices have promising applications in drug delivery and tissue engineering fields.Electrohydrodynamic(EHD)technology is an efficient and economical technique to fabricate different 3D structures and integrate multiple functional materials into one structure to meet different requirements.However,the application of electrohydrodynamic technology in the research and development of biological materials is still under developement,especially in the generation of submicron fibers with high precision arrangement and various internal strucutres.In this study,drug-loaded fibrous matrices with various macroscopic and microcosmic structures were manufactured by hybrid EHD technology,and its applications in controlled release,wound healing and tissue engineering were explored.The main aim of current research can be categorised into four sections.Firstly,fibers with random and well-ordered aligment are desirable for drug delivery.Novel fibrous constructs combing both random and well-ordered depossition were developed from a unique engineering platform.Complex constructs were engineered using EHD printing and electrospinning in an intercalating material layer-by-layer format using a side-by-side technological approach.Here,structure generation proceeded with deposition of ordered polycaprolactone(PCL)fibers enabling well-defined void size and overall dimension,after which randomly spun polyvinyl pyrrolidone(PVP)fibers formed a construct overcoat(as a membrane).Differences between polymer dissolution rate,hydrophilicity,mechanical properties and drug release behaviors of the complex constructs were investigated.In vitro cell studies using human umbilical vein blood vessel cell line demonstrated device biocompatibility and Escherichia Coli(E.coli)was selected to demonstrate anti-bacterial function.Secondly,arrangements of fibers using different materials have significant influence on the properties of fiber composites.In this study,dual-needle EHD co-printing was developed to fabricate unique micron-scaled architectures based on multi-material fibrous(filamentous)morphologies.Two stainless steel needles were used to simultaneously co-print PCL and PVP polymers.Differences in polymer hydrophobicity and dissolution rate was used to modulate drug release(tetracycline hydrochloride,TE-HCL)from various co-printed configurations.The alignment and vertical stacking of both PVP and PCL printed filaments were detected.Process parameters were found to strongly influence co-print construct diameter.TE-HCL release from co-printed formulations exhibited two phases;rapid and sustained.In vitro biological assay demonstrated construct biocompatibility.The present study shows the potential of development and use of simultaneously co-printed filaments in drug delivery.Thirdly,core-shell fibers are revolutionary development in the field of biomaterial and technology.In this study,coaxial EHD printing was utilized to produce well-ordered,dual-drug loaded-magnetic core-shell matrices with high resolution.TE-HCL/PCL solution acted as the shell formulation and lidocaine hydrochloride(LH)/poly(ethylene oxide)(PEO)solution acted as the core formulation.It was found that the concentration of PEO solution could influence the resulting coaxial structures.The inner core of coaxial fibers increased with increasing concentration of PEO solution.In addition,adding iron oxide(Fe3O4)NPs and varying concentration of TE-HCL within the PCL shell layer would have an effect on mechanical properties,release behaviors and cell behaviors of core-shell matrices.Results showed rapid release of LH located in the PEO core fibers while TE-HCL loaded in the shell PCL fibers was released sustainably from the coaxial printing matrices.The coaxial drug-loaded matrices also had good bioactivity,indicating the potential of the printed fibers in wound dressings.Finally,micron fibers with muiti-inernal structure have presented unusual potential for use in many novel applications.An EHD printing method were developed to fabricate graphene loaded PCL/PEO dual-core matrices for nerve tissue engineering in this research.Graphene were incorporated in shell PCL components,while gelatin and dopamine hydrochloride(DAH)were encapsulated in two PEO fluids to enhance the biocompatibility of the graphene loaded matrices.Furthermore,the effect of PEO concentration on the formation of dual-core fibers were evaluated.Besides,the influence of process parameters on the morphology of multi-compartment fibers were also detected.The graphene loaded dual-core matrices had two inner chambers and increasing the quantity of graphene in the matrices would make the surface smoother.Meanwhile,the addition of graphene also resulted in the reduction of elasticity of the matrices.The biological results indicated that graphene loaded dual-core matrices had good biocompatibility and could improve the migration for PC 12 cells,suggesting its potential to be applied in nerve restoration.