Abstract

Beta-tricalcium phosphate (β-TCP)-based bioinks were developed to support direct-ink 3D printing-based manufacturing of macroporous scaffolds. Binding of the gelatin:β-TCP ink compositions was optimized by adding carboxymethylcellulose (CMC) to maximize the β-TCP content while maintaining printability. Post-sintering, the gelatin:β-TCP:CMC inks resulted in uniform grain size, uniform shrinkage of the printed structure, and included microporosity within the ceramic. The mechanical properties of the inks improved with increasing β-TCP content. The gelatin:β-TCP:CMC ink (25:75 gelatin:β-TCP and 3% CMC) optimized for mechanical strength was used to 3D print several architectures of macroporous scaffolds by varying the print nozzle tip diameter and pore spacing during the 3D printing process (compressive strength of 13.1 ± 2.51 MPa and elastic modulus of 696 ± 108 MPa was achieved). The sintered, macroporous β-TCP scaffolds demonstrated both high porosity and pore size but retained mechanical strength and stiffness compared to macroporous, calcium phosphate ceramic scaffolds manufactured using alternative methods. The high interconnected porosity (45–60%) and fluid conductance (between 1.04 ×10−9 and 2.27 × 10−9 m4s/kg) of the β-TCP scaffolds tested, and the ability to finely tune the architecture using 3D printing, resulted in the development of novel bioink formulations and made available a versatile manufacturing process with broad applicability in producing substrates suitable for biomedical applications.

Highlights

  • Ceramics, such as synthetic calcium phosphates, have attracted the interest of biomedical researchers and have been used in implant applications in bone [1]

  • The 1%-CMCcontaining bioink was very similar to the initial bioinks without CMC, while addition of 5% CMC made the resultant bioinks very viscous (Supplementary Fig. S1 shows rheological information) at the 70 kPa print pressure and prevented their use in 3D printing

  • Scanning electron microscopy (SEM) micrographs of the printed surface revealed that the average grain size of the 65% β-TCP plus 3% CMC, 70% β-TCP plus 3% CMC and 75% β-TCP plus 3% CMC scaffolds were 5.85 ± 0.176 μm, 7.52 ± 0.269 μm, and 6.33 ± 0.171 μm, respectively (Fig. 1b)

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Summary

Introduction

Ceramics, such as synthetic calcium phosphates, have attracted the interest of biomedical researchers and have been used in implant applications in bone [1]. In such case, the material choice proved judicious because calcium phosphates have similar chemical composition and structure as native bone and are, biocompatible. In order to obtain new tissue formation (the ultimate objective of all tissue engineering endeavors), the ceramic scaffolds must provide appropriate architecture (e.g., open and highly porous structures) and appropriate chemical cues (e.g., select ions and growth factors that promote cell functions pertinent to new tissue formation), and scaffold-material degradation synchronous with the rate of new tissue formation [5, 6]. In the case of bone-related applications, the dynamic milieu of that tissue requires that the ceramic scaffolds must have appropriate mechanical properties; in this respect, ceramics have limitations since they undergo brittle failure under compressive loading

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