3D Bio-Printability of Hybrid Pre-Crosslinked Hydrogels.

Cartwright Nelson,Slesha Tuladhar,Ahasan Habib,Loren Launen

doi:10.3390/ijms222413481

Cartwright Nelson, Slesha Tuladhar + Show 2 more

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https://doi.org/10.3390/ijms222413481

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Abstract

Maintaining shape fidelity of 3D bio-printed scaffolds with soft biomaterials is an ongoing challenge. Here, a rheological investigation focusing on identifying useful physical and mechanical properties directly related to the geometric fidelity of 3D bio-printed scaffolds is presented. To ensure during- and post-printing shape fidelity of the scaffolds, various percentages of Carboxymethyl Cellulose (CMC) (viscosity enhancer) and different calcium salts (CaCl2 and CaSO4, physical cross-linkers) were mixed into alginate before extrusion to realize shape fidelity. The overall solid content of Alginate-Carboxymethyl Cellulose (CMC) was limited to 6%. A set of rheological tests, e.g., flow curves, amplitude tests, and three interval thixotropic tests, were performed to identify and compare the shear-thinning capacity, gelation points, and recovery rate of various compositions. The geometrical fidelity of the fabricated scaffolds was defined by printability and collapse tests. The effect of using multiple cross-linkers simultaneously was assessed. Various large-scale scaffolds were fabricated (up to 5.0 cm) using a pre-crosslinked hybrid. Scaffolds were assessed for the ability to support the growth of Escherichia coli using the Most Probable Number technique to quantify bacteria immediately after inoculation and 24 h later. This pre-crosslinking-based rheological property controlling technique can open a new avenue for 3D bio-fabrication of scaffolds, ensuring proper geometry.

Highlights

Stefano Sivolella and Alfredo RoncaIn recent years, the horizon of tissue engineering and regenerative medicine (TERM)has been expanding vastly due to a revolutionary fabrication technology called 3D bioprinting and the availability of biomaterials compatible with this technique [1]
For the first time, we proposed hybrid hydrogels consisting of alginate and carboxymethyl cellulose (CMC) for the extrusion-based bioprinting process [48,49,50,51]
CMC is a copolymer of β-D-glucose and β-D-glucopyranose-2-O-(carboxymethyl)-mono-sodium salt, which is connected via β-1,4-glucosidic bonds [54]

Summary

Introduction

Stefano Sivolella and Alfredo RoncaIn recent years, the horizon of tissue engineering and regenerative medicine (TERM)has been expanding vastly due to a revolutionary fabrication technology called 3D bioprinting and the availability of biomaterials compatible with this technique [1]. Various bioprinting processes provide spatial control and repeatability of material deposition for attaining design specific 3D tissue scaffolds. Achieving controlled spatiality of the fabricated 3D scaffold with hydrogel materials is still challenging [14]. Different hydrogel materials are blended to prepare a hybrid hydrogel with an expectation of achieving the required properties of bio-ink and final structure [15,16]. Those properties can be categorized as rheological, mechanical, shape fidelity, interlayer attraction, cytotoxicity, and degradability [17]. Material with improper rheological properties may not develop enough mechanical properties, such

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