Research On High Precision 3D Printing Technology Of Nerve Scaffold Based On Hydrogel Bio-ink

Peripheral nervous system is an important part of the human nervous system.Traumatic injury usually leads to peripheral nerve injury,and in severe cases,it will lead to neurological dysfunction,which will bring heavy burden to families and society.Although considerable progress has been made in microsurgery,nerve grafts are still needed to repair large space peripheral nerve injuries.Due to the limited source of autologous nerve transplantation and the loss of donor function,the research and development of artificial nerve scaffold for repairing peripheral nerve defects has become a hot research.In view of the difficulty in processing nerve scaffold with both physical and biological guidance signals,this paper preparing nerve scaffold with hydrogel bio-ink as the material by extrusion 3D printing method,and studying the mechanical behavior,printing process and gradient technology.Firstly,a quantitative test method for the printing performance of hydrogel bio-ink was proposed.Parameters of collagen hydrogel creep recovery curve was identified by using four element model.The identified parameters were input into COMSOL for simulation,and the deformation of collagen with different concentrations over time was obtained.According to the principle of extrusion printing and the viscoelasticity of hydrogel materials,the transport dynamics models of single material and two-component gradient hydrogel materials in printing process were established through theoretical formula derivation.At the same time,the 3D printing experimental platform needed to verify the mechanical model and theory is introduced.Then,a new plastic injector was designed to verify the single material printing control model.The printing process of gelatin core dissolving nerve scaffold was studied,and the parameters of three different concentrations of collagen nerve scaffold were evaluated.It was found that 5% collagen was suitable for preparing nerve scaffold.The printing process of nano-clay core disolving nerve scaffold was studied,and the removal process of nano-clay core disolving nerve scaffold was proposed,which was freeze-dried first and then washed with PBS buffer.The biological experiment of nerve scaffold was carried out,and the animal experiment results showed that the microtubule array nerve scaffold had a repairing effect on nerve defects.Finally,a two-component gradient printing nozzle was designed,and the control model of two-component gradient printing was verified through high-frequency and low-frequency gradient change experiments.The printing process of one-dimensional and two-dimensional gradient changes was studied.The red-and-white one-dimensional gradient structure and two-dimensional black-and-white portrait pictures were successfully printed by using F127.The gradient printing process of collagen with nerve growth factor was studied,and the collagen hydrogel structure with factor gradient was prepared,which laid the foundation for the study of nerve scaffold with factor gradient.