Extrusion-based 3D printing of poly(propylene fumarate) scaffolds with hydroxyapatite gradients

Abstract

The primary focus of this work is to present the current challenges of printing scaffolds with concentration gradients of nanoparticles with an aim to improve the processing of these scaffolds. Furthermore, we address how print fidelity is related to material composition and emphasize the importance of considering this relationship when developing complex scaffolds for bone implants. The ability to create complex tissues is becoming increasingly relevant in the tissue engineering community. For bone tissue engineering applications, this work demonstrates the ability to use extrusion-based printing techniques to control the spatial deposition of hydroxyapatite (HA) nanoparticles in a 3D composite scaffold. In doing so, we combined the benefits of synthetic, degradable polymers, such as poly(propylene fumarate) (PPF), with osteoconductive HA nanoparticles that provide robust compressive mechanical properties. Furthermore, the final 3D printed scaffolds consisted of well-defined layers with interconnected pores, two critical features for a successful bone implant. To demonstrate a controlled gradient of HA, thermogravimetric analysis was carried out to quantify HA on a per-layer basis. Moreover, we non-destructively evaluated the tendency of HA particles to aggregate within PPF using micro-computed tomography (μCT). This work provides insight for proper fabrication and characterization of composite scaffolds containing particle gradients and has broad applicability for future efforts in fabricating complex scaffolds for tissue engineering applications.

Keywords:

• Viscosity
• composites
• compressive modulus
• bone tissue engineering
• gradient

Abbreviations:

• Atomic force microscopy, AFM
• Analysis of variance, ANOVA
• Phenylbis(246-trimethylbenzoyl)-phosphine oxide, BAPO
• Diethyl fumarate, DEF
• Dimethyl sulfoxide, DMSO
• Extracellular matrix, ECM
• Fourier transform-infrared spectroscopy, FT-IR
• Hydroxyapatite, HA
• (Tukey’s) Honestly Significant Difference test, HSD
• Polydispersity index, PDI
• Poly(propylene fumarate), PPF
• Poly(propylene fumarate)-co-poly(ε-caprolactone), PPF-co-PCL
• Sodium dodecyl sulfate, SDS
• Scanning electron microscopy, SEM
• Stereolithography, STL
• Thermogravimetric analysis, TGA
• Micro-computed tomography, μCT.

Acknowledgments

We acknowledge Dr Matteo Pasquali for his assistance with the viscosity analysis and Dr Marco Santoro for his feedback on the manuscript. We also would like to thank Dr Daniel Puperi for his assistance in developing custom Python code for the compressive mechanical analysis.