Development of 3D Printed Adhesive Tissue Engineering Scaffold
Author(s)
Chen, Shuai
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Abstract
Tissue engineering scaffolds (TESs) are temporary extracellular matrix imitation that facilitate cellular adhesion, growth, proliferation, and differentiation, and provide a suitable environment for promoting tissue regeneration. On the basis of pre-designed models, 3 dimensional printing (3D printing) technology can be utilized to create TESs with desired structures and shapes. In general, TESs need to be fixed onto tissue surface through suturing or bio-glue. Traditional fixation methods have multiple disadvantages, such as secondary damage caused by suturing, and cytotoxicity or possible inflammation caused by bio-glue. The objective of this study is to develop 3D-printed TESs with intrinsic bio-adhesion property that can be adhered to damaged tissues without the help of suturing or bio-glue.
In order to achieve this goal, in the first version of protocol, dopamine grafted hyaluronic acid methacrylate (HAMA-dopa) and gelatin methacryloyl (GelMA) were used as major components in bio-ink. Adhesive tissue engineering scaffolds (ATESs) were prepared by freeform reversible embedding of suspended hydrogels (FRESH) printing and air printing (directly print on the substrate) through extrusion. The bio-adhesion strength of ATESs from the two methods was compared, and the results showed that the adhesion strength of scaffolds prepared by the latter method was stronger. However, as the latter method is not clinically convenient and require sophisticated operation, a type of ATES that could have both high enough in vivo adhesion property and convenient clinical application is required.
In the improved version of protocol for fabricating advanced ATESs, tyramine grafted hyaluronic acid methacrylate (HAMA-tyr), gelatin and GelMA were used as major components in the bio-ink and FRESH printing was adopted as fabrication method. The resulted ATESs are off-the-shelf products that are convenient for clinical application. The ATES in the group with the highest adhesion property was adhered to the heart surface of a mouse model with myocardial infarction, which was kept alive for 4 weeks. The results demonstrated that the ATES had enough in vivo adhesion property to be kept on the tissue surface for a proper time length.
In this study, stereolithography (SL) was also used to prepare ATESs. Compared with extrusion printing, SL has the advantages of high fidelity and short production time. In this study, SL was used to fabricate ATESs with blood vessels or porous structures to demonstrate that the method could be used to produce ATESs with sophisticated internal and external structures.
The mechanical properties, swelling behavior, porosity and cytotoxicity of the materials were tested, and the results showed that the 3D printed ATESs have appropriate properties to be functional scaffolds. The fidelity of printing based on different models was evaluated in micro and bulk perspectives, and the results indicated that 3D printed ATESs could be fabricated with acceptable accuracy based on models. In addition, the in vitro adhesion properties of the ATESs under tensile, shear or dynamic stress in air or underwater were tested, and the results showed that the modification methods being used in this study can improve the adhesion strength of the 3D printed ATESs.
The major target of this study was to develop and fabricate shape/structural designable ATESs with high in vivo adhesion property and application convenience. For achieving the target, advanced fabrication protocol was developed based on the experience of the first version, and bio-ink, printing process and fabrication procedure to produce such ATESs were developed. The in vivo adhesion property of the ATES was demonstrated in a mouse model of myocardial infarction for 4 weeks. In order to accommodate for a variety of application situations, both extrusion printing and stereolithography were used to fabricate the ATESs. The analyze of the other properties, such as mechanical properties, swelling behavior, porosity and cytotoxicity, demonstrated that the ATESs were qualified as a functional scaffold for cell supporting and the procedures for the improvement of adhesion properties would not compromise the function of the ATESs as an appropriate scaffold.
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Date
2023-11-10
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Text
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Dissertation