Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue

Abstract

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 bioinks 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 osteoinducing 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 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 development of this NICE bioink technology toward a realistic clinical process for 3D bioprinting patient-specific bone tissue for regenerative medicine.

Chitosan-Hydrogel Polymeric Scaffold Acts as an Independent Primary Inducer of Osteogenic Differentiation in Human Mesenchymal Stromal Cells

“…Accordingly, morphological and molecular characterization of osteogenic differentiation performed on BM-hMSCs cultured in a 3D aragonite-based bi-phasic osteochondral scaffold confirmed the active role played by the scaffold in supporting osteogenic differentiation and enhancing cell proliferation [21]. Chimene and colleague demonstrated the osteoinductive capability of 3D bioprinted scaffolds on hMSCs, analysing both nascent ECM and transcripts in the absence of osteoinducing agents [22]. Similar results were previously obtained analysing titania containing phosphate-based glasses.…”

3D Printing of Strong and Tough Double Network Granular Hydrogels

“…A prerequisite for inks to be 3D printed into macroscopic complex structures is their shear-thinning behavior, which is a common property of bioinks [44,45] and jammed microgels. [46] To ensure a reproducible jamming of the microgels, we measure the solid polymer content of samples swollen in deionized water, as reported in Table S1, Supporting Information.…”

3D Bioprinted Bacteriostatic Hyperelastic Bone Scaffold for Damage-Specific Bone Regeneration

“…While a variety of bioink materials have been tested in additive manufacturing of bone-like scaffolds, demonstrating promising in vitro and in vivo osteoconductivity, such scaffold-based therapies have shown only a modest success in clinical applications [24,25]. This is mainly due to the lack of proper osteoconductive cues in the bioink, biomaterial-related infections, insufficient engraftment, and inadequate reproducibility and patient-specificity [26,27].…”