3D Bioprinting of Multifunctional Dynamic Nanocomposite Bioinks Incorporating Cu‐Doped Mesoporous Bioactive Glass Nanoparticles for Bone Tissue Engineering

Abstract

Bioprinting has seen significant progress in recent years for the fabrication of bionic tissues with high complexity. However, it remains challenging to develop cell‐laden bioinks exhibiting superior physiochemical properties and bio‐functionality. In this study, a multifunctional nanocomposite bioink is developed based on amine‐functionalized copper (Cu)‐doped mesoporous bioactive glass nanoparticles (ACuMBGNs) and a hydrogel formulation relying on dynamic covalent chemistry composed of alginate dialdehyde (oxidized alginate) and gelatin, with favorable rheological properties, improved shape fidelity, and structural stability for extrusion‐based bioprinting. The reversible dynamic microenvironment in combination with the impact of cell‐adhesive ligands introduced by aminated particles enables the rapid spreading (within 3 days) and high survival (>90%) of embedded human osteosarcoma cells and immortalized mouse bone marrow‐derived stroma cells. Osteogenic differentiation of primary mouse bone marrow stromal stem cells (BMSCs) and angiogenesis are promoted in the bioprinted alginate dialdehyde‐gelatin (ADA‐GEL or AG)‐ACuMBGN scaffolds without additional growth factors in vitro, which is likely due to ion stimulation from the incorporated nanoparticles and possibly due to cell mechanosensing in the dynamic matrix. In conclusion, it is envisioned that these nanocomposite bioinks can serve as promising platforms for bioprinting complex 3D matrix environments providing superior physiochemical and biological performance for bone tissue engineering.

Biomimetic Mineralized Hydroxyapatite Nanofiber-Incorporated Methacrylated Gelatin Hydrogel with Improved Mechanical and Osteoinductive Performances for Bone Regeneration

“…More importantly, their microstructures are similar to that of the natural extracellular microenvironment, which is favorable for cell growth and tissue regeneration. 7 , 8 Polysaccharide-type natural polymers, such as hyaluronate, 9 alginate and chitosan, 10 , 11 protein-type natural polymers, such as gelatin and collagen, 12 , 13 and synthetic polymers, such as poly(N-isopropylacrylamide) and poly(ethylene glycol), 14 , 15 have all been well studied. In particular, gelatin is a collagen derivative with many beneficial biological features, such as the matrix metalloproteinase (MMP)-sensitive degradation sites and the Arg-Gly-Asp (RGD) sequence, which facilitates cell migration, adhesion and differentiation.…”

Non-additive effect of the DNA methylation inhibitor, 5-Aza-dC, and glass as a culture surface on osteogenic differentiation

“…Glass has been used as an osteo-inductive material for bone regeneration in orthopedic and dentistry applications for several years [ 46 , 47 ]. In addition, glass nanoparticles were included as a component of bio-inks to enhance bone tissue engineering [ 48 , 49 ]. In the present study, we combine the two factors, i.e., epigenetic modifier pretreatment and the culture surface, aiming to obtain the maximum differentiation efficiency.…”

Enhancing Stem Cell-Based Therapeutic Potential by Combining Various Bioengineering Technologies

“…Currently, multipotent MSCs are one of the most popular stem cell types used in 3D bioprinting, probably due to the relative ease to culture in vitro and high self-renewability, multipotency, and high safety (low immunogenicity and tumorigenicity) compared with other types of stem cells ( Skeldon et al, 2018 ). Zhu et al (2022) developed 3D-bioprinted bone-like tissue scaffolds using BM-MSCs and multifunctional nanocomposite bioink consisting of alginate dialdehyde-gelatin and mesoporous bioactive glass nanoparticles. Similarly, Costantini et al (2016) fabricated hydrogel cartilage scaffolds loaded with 3D-bioprinted BM-MSCs using a bioink consisting of chondroitin sulfate amino ethyl methacrylate, gelatin methacrylamide, and hyaluronic acid methacrylate.…”