There has been an uptick in research activities focusing on 3D bioprinting for bone regeneration. In this issue of “From Academia”, we included four recent publications tackling the issue from different angles. The first article focuses on a new 3D printing composite using silicone resing derived larnite/C scaffold to create new regeneration and treatment strategies for bone tumor patients. The second study focuses on a new bio-ink for 3D bioprinting bone, nanoengineered ionic covalent entanglement (NICE) bioink formulation, which not only showed good printability, mechanical properties, biodegradability, but also the ability to induce endochondral differentiation of encapsulated human mesenchymal stem cells (hMSCs) in the absence of an osteoinductive agent on a genetic level. In the third study, researchers developed a new PLA-based composite formulation that could be used to produce bone scaffold and regeneration. In the last article, a new iron-based ink formulation, as well as matching 3D printing, de-binding, and sintering conditions, was developed to create iron scaffolds with a porosity of 67%, pore interconnectivity of 96%, and a strut density of 89% after sintering. The study shows the great potential of extrusion-based 3D printed porous iron to be further developed as a biodegradable bone substituting biomaterial. “From Academia” features recent, relevant, close to commercialization academic publications. Subjects include but not limited to healthcare 3D printing, 3D bioprinting, and related emerging technologies.
Email: Rance Tino (firstname.lastname@example.org) if you want to share relevant academic publications with us.
Silicone resin derived larnite/C scaffolds via 3D printing for potential tumor therapy and bone regeneration
Authored by Shengyang Fu, Haoran Hu, Jiajie Chen, Yufang Zhu, Shichang Zhao. Chemical Engineering Journal. 15 February 2020
Three-dimensional (3D) printing has been used to fabricate bioceramic scaffolds for treating tumor-related defects in recent years, but the fabrication process and the introduction of anti-tumor agents are still challenging.
In this study, porous free carbon-embedding larniteIn this study, porous free carbon-embedding larnite (a calcium silicate mineral with formula: Ca₂SiO₄. ) (larnite/C) scaffolds have been successfully fabricated by 3D printing of the silicone resin loaded with CaCO3 filler and high-temperature treatment under an inert atmosphere. The fabricated larnite/C scaffolds had uniform interconnected macropores (ca. 400 μm) and exhibited excellent photothermal effect, which was able to kill human osteosarcoma cells (MNNG/HOS) and inhibit the tumor growth in nude mice.
Moreover, the larnite/C scaffolds could stimulate the expression of the osteogenesis-related genes (ALP, OCN, and Runx-2) in rat bone mesenchymal stem cells (rBMSCs), and also promoted new bone formation in critical-sized rat calvarial defects. Therefore, the combination of 3D printing with polymer-derived ceramics strategy could fabricate multifunctional bioceramic scaffolds, which would be promising for potential application in treating tumor-related bone defects.
Authored by David Chimene, Logan Miller, Lauren M. Cross, Manish K. Jaiswal, Irtisha Singh, and Akhilesh K. Gaharwar. ACS Applied Materials & Interfaces. 24 February 2020
Bioprinting is an emerging additive manufacturing approach to the fabrication of patient-specific, implantable three-dimensional (3D) constructs for regenerative medicine.
However, developing cell-compatible bioinks with high printability, structural stability, biodegradability, and bioactive characteristics is still a primary challenge for translating 3D bioprinting technology to preclinical and clinal models. To overcome this challenge, we developed a nanoengineered ionic covalent entanglement (NICE) bioink formulation for 3D bone bioprinting.
The NICE bio-inks allow precise control over printability, mechanical properties, and degradation characteristics, enabling custom 3D fabrication of mechanically resilient, cellularized structures. We demonstrate cell-induced remodeling of 3D bioprinted scaffolds over 60 days, demonstrating deposition of nascent extracellular matrix proteins. Interestingly, the bioprinted constructs induce endochondral differentiation of encapsulated human mesenchymal stem cells (hMSCs) in the absence of an osteoinductive agent.
Using next-generation transcriptome sequencing (RNA-seq) technology, we establish the role of nanosilicates, a bioactive component of NICE bioink, to stimulate endochondral differentiation at the transcriptome level. Overall, the osteoinductive bioink has the ability to induce the formation of osteo-related mineralized extracellular matrix by encapsulated hMSCs in growth factor-free conditions.
Furthermore, we demonstrate the ability of NICE bioink to fabricate patient-specific, implantable 3D scaffolds for repair of craniomaxillofacial bone defects. We envision the development of this NICE bioink technology toward a realistic clinical process for 3D bioprinting patient-specific bone tissue for regenerative medicine.
Biocompatible heterogeneous bone incorporated with polymeric biocomposites for human bone repair by 3D printing technology
Authored by Meiling Wan Shuifeng Liu Da Huang Yang Qu Yang Hu Qisheng Su Wenxu Zheng Xianming Dong Hongwu Zhang Yen Wei Wuyi Zhou. Journal of Applied Polymer Science. 24 November 2020
Polylactic acid (PLA) has become a popular polymer material due to its superior biocompatibility. At present, there is little relevant research on heterogeneous bone powder. Besides, the poor dispersibility and adhesivity of inorganic particles in the organic phase remain a problem.
In this study, the pork bone powders were modified with N‐butanol to improve their dispersibility and compatibility in the PLA matrix. In addition, polybutylene succinate‐co‐terephthalates (PBSA) was applied as the flexibility to further reinforce the mechanical properties of materials. The composite filaments with a diameter of 1.75 ± 0.05 mm containing 10 wt% of modified bone powder, 10 wt% PBSA and 80 wt% PLA were prepared by a melt blending method.
The obtained results showed that modified particles were uniformly dispersed within the PLA matrix and improved the mechanical properties of the composite filaments with a tensile strength of 48.5 ± 0.2 MPa and bending strength of 79.1 ± 0.1 MPa and a notch impact strength of 15.8 ± 0.3 kJ/m2.
And the prepared composite materials contained low cytotoxicity, high biocompatibility, and printability, which verified the feasibility of it in 3D printing personalized bone repair applications. This provides a theoretical basis for further research on the effect of bone repair in vivo. Therefore, the composite material will have potential applications such as making customized bones and bone scaffolds by three-dimensional printing technology.
Authored by N.E. Putra, M.A. Leeflang, M. Minneboo, P. Taheri, L.E. Fratila-Apachitei, J.M.C. Mol, J. Zhou, A.A. Zadpoor. Acta Biomaterialia. May 2020
Extrusion-based 3D printing followed by de-binding and sintering is a powerful approach that allows for the fabrication of porous scaffolds from materials (or material combinations) that are otherwise very challenging to process using other additive manufacturing techniques.
Iron is one of the materials that have been recently shown to be amenable to processing using this approach. Indeed, a fully interconnected porous design has the potential of resolving the fundamental issue regarding bulk iron, namely a very low rate of biodegradation.
However, no extensive evaluation of the biodegradation behavior and properties of porous iron scaffolds made by extrusion-based 3D printing has been reported.
Therefore, the in vitro biodegradation behavior, electrochemical response, the evolution of mechanical properties along with biodegradation, and responses of an osteoblastic cell line to the 3D printed iron scaffolds were studied.
An ink formulation, as well as matching 3D printing, de-binding, and sintering conditions, was developed to create iron scaffolds with a porosity of 67%, pore interconnectivity of 96%, and a strut density of 89% after sintering. X-ray diffractometry confirmed the presence of the α-iron phase in the scaffolds without any residuals from the rest of the ink.
Owing to the presence of geometrically designed macropores and random micropores in the struts, the in vitro corrosion rate of the scaffolds was much improved as compared to the bulk counterpart, with 7% mass loss after 28 days. The mechanical properties of the scaffolds remained in the range of those of trabecular bone despite 28 days of in vitro biodegradation.
The direct culture of MC3T3-E1 preosteoblasts on the scaffolds led to a substantial reduction in living cell count, caused by a high concentration of iron ions, as revealed by the indirect assays. On the other hand, the ability of the cells to spread and form filopodia indicated the cytocompatibility of the corrosion products. Taken together, this study shows the great potential of extrusion-based 3D printed porous iron to be further developed as a biodegradable bone substituting biomaterial.