Research Of Multi-scale Tissue Engineering Scaffold Based On Additive Manufacturing

Tissue engineering scaffolds have been widely used in tissue engineering because they act as carriers for cell adhesion and produce a cellular microenvironment for tissue regeneration.The ideal tissue engineering scaffold needs to have both good biocompatibility and sufficient mechanical strength.It is a dilemma for scaffolds to meet both needs above.The normal strategy is mixing or coating other materials to improve the biocompatibility.However,the addition of other materials during the modification of the coating makes the scaffold difficult in clinical.Could we solve this dilemma by simply adjusting the scaffold structure?Since the cell size is about 10 microns,could the compatibility of conventional scaffolds be greatly improved by the introduction of ultrafine fibers(2-5 μm)?This thesis combines fused deposition modeling and fused near-field direct writing technology to develop a macro-micro multi-scale additive manufacture platform,using a single nozzle to achieve multi-scale tissue engineering scaffolds with good biocompatibility and mechanical strength,The micro-scale scaffold(5-20μm)provides a better interface for cell adhesion,and the macro-scale scaffold(200-600 μm)provides adequate mechanical properties.The specific work of the thesis is as follows:Firstly,a macro-micro multi-scale scaffold additive manufacturing platform was built.Through the air pressure and high-voltage control system,the integration of melt extrusion process and the fused near-field direct writing process on a single nozzle was realized.Biodegradable polycaprolactone(PCL)material was used to print fibers ranged from 200-600μm and 5-20μm.Secondly,we systematically studied the micro-scale scaffold.At first,the influence of temperature,pressure,and speed on the diameter of micro-scale fiber was discussed.Next,in order to mimic the complex micro-structure of real tissues,it was proposed to compensate the error caused by the lag effect during the printing process.By the speed regulation,the complex structure with multiple acute corners were obtained.For example,spider webs,flowers,and snail-like complex patterns were successfully printed.Then,we systematically studied macro-micro multi-scale scaffold process.Since the sequence of fused near field direct writing and fused deposition modeling process has great impact on the quality of printed scaffolds,we tried to find a better printing sequence.Furthermore,the influence of different printing speed and gap distance on fiber deposition was discussed.Secondly,in order to mimic the specific microstructure of the in-vivo tissue,the multi-scale scaffold with controllable filling patterns could be successfully printed by specially designed printing path.Finally,we studied the biocompatibility of the scaffold.To demonstrate the multi-scale scaffold biocompatibility,bone mesenchymal stem cells(BMSCs)were seeded on the multi-scale scaffolds fabricated above.The cell growth on the scaffold was evaluated by experiments such as cell adhesion,proliferation,activity,and morphology.The results show that the cells were easy to adhere to the scaffold,and a high proliferation rate,cell activity and good growth state were observed due to the presence of micro-scale fibers.