Research On Optimal Control Of Three-Dimensional Bio-Printing Hydrogel Scaffolds Based On Optical Coherence Tomography

As an important component of tissue engineering,scaffolds provide the necessary space and environment for cell growth.Also its chemical composition and physical structure can affect cell activities,such as cell adhesion,migration,proliferation and differentiation.Hydrogels have good biocompatibility,biodegradable,hydrophilic and power of encapsulating cells,which have been widely applied to construct tissue engineering scaffolds.According to the pre-designed geometry,3D bio-printing technology can prepare the fully connected 3D structure nontoxic and easily.Thus it has become a good tool to manufacture scaffolds,which will be used in cell inoculation or cell package.Combining the hydrogel with 3D Bio-printing technology provides a controllable solution for developing cell seeding / package scaffolds.Tissue engineering scaffolds were fabricated by 3D bio-printing,and its internal porous geometry is tailed to obtain desired geometrical,mechanical or fluid transport properties.However,because of the inherent characteristics of the hydrogels,it is difficult to produce customized porous structures matching the envisioned morphological and physical requirements directly.Current studies have confirmed that there are significant differences in morphological parameters between the printed structure and the design,which seriously affect the practical application of the hydrogel scaffolds.Thus,it is important that the custom structure which matching the expected morphological parameters should be created.Therefore,we propose a method that optimizing the three-dimensional hydrogel scaffold biological stability and controllability.Firstly,we achieve the quantitative characterization of three-dimensional printing hydrogel scaffold structure,then feedback on design and print of scaffold based on characterization results,after that reduce the morphological differences between design and print based on iteration,finally,improve the stability of the hydrogel scaffold controllability.The key to this method is how to achieve a scaffolds' high-resolution,non-invasive online quantitative characterization.Thus this paper presents the approach which based on optical coherence tomography technology.The method follows:The first closed loop is called as "experimental" group,used to evaluate the hydrogel scaffolds' internal controllability.The hydrogel scaffolds with different pore sizes were designed,printed,imaged and analyzed by the swept source OCT system.The quantitative characterization include pore size,strut thickness,porosity,surface area and scaffold volume,and compare with the original design parameters.The second closed loop is called as "production" group,the mismatch between the designed and as-printed morphology was used as input,difference correlation analysis and 3D printing process optimization were also integrated to decrease the mismatch.The effectiveness of the compensation was verified at the end of the printing run with optimized printing parameters setting.For example,for the averaged pore size,the mismatch decreased from 30% to 2%.It shows that it is feasible to predict and precise control three-dimensional biological hydrogel scaffold based on OCT technology.Also it concludes that,OCT can further expand its application in the field of tissue engineering,and may be a key tool for scaffold design and characterization,3D bio-printing process control,the engineered tissues monitor in vitro.