Enhancement Of Thermal-Sensitive Hydrogels For Extrusion-Based 3D Bioprinting

Thermal-sensitive hydrogels are smart materials based on temperature response,which can reversibly transit between gel and sol state via temperature regulation.Due to this mechanism,this kind of materials can be as an ideal ink for extrusion-based 3D bioprinting by changing temperature.Unfortunately,the gelation process based on hydrophilic-hydrophobic interaction is too weak for some of these materials to meet the requirement of 3D printing.Thus,reinforcement of hydrogels is one of the research orientations in exploiting the printable materials.In this thesis,the aliphatic polyester-poly（ethylene glycol）（PEG）block copolymers formed thermal-sensitive hydrogels were used for the investigation.Thus,a series of fast and efficient strategy of materials enhancement was proposed.The details are introduced as follows:Firstly,a series of PCL-PEG-PCL triblock copolymers with different molecular weight were prepared,in which poly（ε-caprolactone）（PCL）is highly crystallized biodegradable polymer.This copolymer formed hydrogels exhibited partial crystallized properties.Compared with amorphous gels,the thermal stability and rheological properties of the partial crystalline ones were improved.Through optimizing the molecular weight and the composition ratio of each block,the degree of crystallinity was maximized.The PCL-PEG-PCL formed hydrogel with optimized crystallinity can not only be extruded and printed via temperature adjustment,but also the three-dimensional printed structure can be effectively maintained with high resolution.Furthermore,the amorphous triblock copolymers,poly（ε-caprolactone/lactide）-b-poly（ethylene glycol）-b-poly（ε-caprolactone/lactide）（PCLA-PEG-PCLA）,were enhanced by the introduction of cellulose nanocrystals（CNC）,which is a kind of rigid,hydrophilic and biocompatible nanomaterials.Similarly,the addition of CNC significantly improved the thermal stability and mechanical properties of the hydrogels,and within a certain range,the enhancement effect was directly proportional to the concentration of CNC.More importantly,the CNC enhanced PCLA-PEG-PCLA hydrogels could also be extruded and printed via temperature regulation.The printed objects had high resolution and fidelity with effectively maintained structure.Finally,the gelatin methacryloyl（Gel MA）has been focused as a bioink over time.In this thesis,the difference of physicochemical property between modified and unmodified gelatin,as well as the mechanical strength between before and after photopolymerization,was systematically investigated.The cell compatibility was also evaluated by using two different kinds of cells.Moreover,Gel MA was also used as a macromolecular crosslinking agent to copolymerized with methacrylic acid（MAA）after printing.This gel can be further enhanced via the coordination interaction between Fe³⁺and carboxy group.Based on transient structural anisotropy during the 3D printing and photo-gelation,these hydrogels can be programmable reversible shape transformed between water and Fe Cl₃ solution.