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Abstract Additive manufacturing is a promising method for producing customized 3D bioactive constructs for regenerative medicine. Here, 3D printed highly osteogenic scaffolds using nanoengineered ionic–covalent entanglement ink (NICE) for bone tissue engineering are reported. This NICE ink consists of ionic–covalent entanglement reinforced with Laponite, a 2D nanosilicate (nSi) clay, allowing for the printing of anatomic‐sized constructs with high accuracy. The 3D printed structure is able to maintain high structural stability in physiological conditions without any significant swelling or deswelling. The presence of nSi imparts osteoinductive characteristics to the NICE scaffolds, which is further augmented by depositing pluripotent stem cell‐derived extracellular matrix (ECM) on the scaffolds. This is achieved by stimulating human induced pluripotent stem cell‐derived mesenchymal stem cells (iP‐hMSCs) with 2‐chloro‐5‐nitrobenzanilide, a PPARγ inhibitor that enhances Wnt pathway, resulting in the deposition of an ECM characterized by high levels of collagens VI and XII found in anabolic bone. The osteoinductive characteristics of these bioconditioned NICE (bNICE) scaffolds is demonstrated through osteogenic differentiation of bone marrow derived human mesenchymal stem cells. A significant increase in the expression of osteogenic gene markers as well as mineralized ECM are observed on bioconditioned NICE (bNICE) scaffolds compared to bare scaffolds (NICE). The bioconditioned 3D printed scaffolds provide a unique strategy to design personalized bone grafts for in situ bone regeneration.
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Biomimetic 3D Printing of Hierarchical and Interconnected Porous Hydroxyapatite Structures with High Mechanical Strength for Bone Cell Culture
Human bone demonstrates superior mechanical properties due to its sophisticated hierarchical architecture spanning from the nano/microscopic level to the macroscopic. Bone grafts are in high demand due to the rising number of surgeries because of increasing incidence of orthopedic disorders, non‐union fractures, and injuries in the geriatric population. The bone scaffolds need to provide porous matrix with interconnected porosity for tissue growth as well as sufficient strength to withstand physiological loads, and be compatible with physiological remodeling by osteoclasts/osteoblasts. The‐state‐of‐art additive manufacturing (AM) technologies for bone tissue engineering enable the manipulation of gross geometries, for example, they rely on the gaps between printed materials to create interconnected pores in 3D scaffolds. Herein, the authors firstly print hierarchical and porous hydroxyapatite (HAP) structures with interconnected pores to mimic human bones from microscopic (below 10 µm) to macroscopic (submillimeter to millimeter level) by combining freeze casting and extrusion‐based 3D printing. The compression test of 3D printed scaffold demonstrates superior compressive stress (22 MPa) and strain (4.4%). The human mesenchymal stromal cells (MSCs) tests demonstrate the biocompatibility of printed scaffold.
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- Award ID(s):
- 1656006
- PAR ID:
- 10080887
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Engineering Materials
- Volume:
- 21
- Issue:
- 1
- ISSN:
- 1438-1656
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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