Study On Additive-equal Composite Material Forming With Micro-nano Structure And Its Application In Soft Tissue Reparation

With the continuous progress of society and the rapid development of national economy,people have a stronger desire to improve living standards and quality of life.Under this background,the demand for tissue and organ defect repair has attracted more and more attention.In fact,traffic accidents,extreme work,serious and chronic diseases such as cardiovascular and cerebrovascular diseases and tumors will lead to organ defects,which has become one of the important contents of clinical treatment,and the attention and clinical needs in this field are becoming increasingly prominent with the intensification of social aging.As the theoretical basis of constructing artificial tissues and organs in vitro,the technical connotation of tissue engineering and regenerative medicine has been derived and expanded in the direction of interdisciplinary.The new technology field of biological manufacturing,which is formed by the cross integration of tissue engineering,biomaterials and advanced manufacturing technology,has shown great development potential in the construction of artificial tissues and organs in vitro.The representative advanced manufacturing technologies covered mainly include additive manufacturing,micro nano manufacturing,electrospinning and other technologies.Moreover,due to the unique anisotropic fiber structure and micro nano topology of natural tissues,The internal components are also extremely rich.It is often difficult to realize the cross-scale controllable forming of multiple materials with a single manufacturing technology.Therefore,more and more research began to pay attention to the composite of multiple processes to prepare artificial organ repair materials.In this context,starting from the common problems of soft tissue repair,this paper proposes to integrate the characteristics of various technologies such as material modification,electrostatic direct writing,electrospinning and micro embossing,innovatively gives an equal material micro nano composite molding technology,focuses on the process parameter design and optimization method to ensure the molding quality,and builds a biological manufacturing system platform that can realize the proposed composite molding process,The work of using the proposed molding technology and system platform to construct artificial blood vessels that can be used for small-diameter blood vessel replacement and repair scaffolds for tissue defects caused by fundus lesions was explored.The feasibility and effectiveness of the constructed samples were verified by cell inoculation experiment and mechanical property characterization.The specific research results of this paper mainly include:1)Starting from the common problems of soft tissue repair,an innovative micro nano composite molding process of additive materials is proposed,which combines the technical characteristics of micro imprinting,electrostatic direct writing,electrostatic spinning and material surface modification.The characteristics of micro imprinting technology can effectively ensure the mechanical properties of thin-walled structures,and electrostatic direct writing can form controllable bionic microstructures on thin-walled structures,Electrospinning and material surface modification technology can achieve the function of packaging and biological performance optimization in the three-dimensional tubular shaping of thin-walled structure.These technical characteristics show unique advantages in meeting the mechanical and structural bionics in the bionic construction of soft tissue.2)For the micro nano composite molding process of additive materials proposed above,the corresponding biological manufacturing system platform is studied and developed,focusing on the electro-hydraulic printing module including man-machine interface and the embossing module with controllable temperature gradient.The design and optimization methods of key process parameters affecting the final sample preparation performance during multi module collaborative preparation are studied,and the experimental verification of sample preparation is carried out.3)According to the construction requirements of small-diameter artificial blood vessels(diameter less than 6mm,pipe wall thickness 300-500 microns,and pipe wall contains typical three-layer structure),combined with the composite forming process proposed above,and further starting from the temperature sensitive properties of the material,it is proposed to controllably curl the composite formed film into a tube through a millimeter level tubular mold,and wrap it with electrospinning,so as to finally obtain the forming process of small-diameter artificial blood vessel samples,On this basis,the effects of material surface modification and electrostatic direct writing microstructure on the growth of endothelial cells guided by the final vascular inner wall were studied;Through the characterization of mechanical properties,the mechanical properties of twodimensional thin-walled structure and three-dimensional plastic pipe,the feasibility of the proposed forming process and technology in constructing smalldiameter artificial blood vessel is further analyzed and verified.4)Starting from the structural requirements of the repair scaffold for human retinal pigment epithelium(RPE)lesions(the 3.5 mm*6mm film with a thickness of 6 microns is covered with 30 microns of non-through hole structure)and the mechanical properties required for minimally invasive delivery,it is proposed to prepare the surface microstructure of RPE scaffold based on the above composite molding process idea and further combine lithography technology and mold turning technology,taking into account the cell biocompatibility,The surface modification method of the scaffold is given.Finally,the performance of the prepared samples and the feasibility of the proposed process are verified by experiments.