TY - JOUR
T1 - Conditioning of 3D Printed Nanoengineered Ionic–Covalent Entanglement Scaffolds with iP-hMSCs Derived Matrix
AU - Sears, Candice
AU - Mondragon, Eli
AU - Richards, Zachary I.
AU - Sears, Nick
AU - Chimene, David
AU - McNeill, Eoin P.
AU - Gregory, Carl A.
AU - Gaharwar, Akhilesh K.
AU - Kaunas, Roland
N1 - Funding Information:
C.S. and E.M. contributed equally to this work. A.K.G. would like to acknowledge financial support from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) of the National Institutes of Health (NIH) Director's New Innovator Award (DP2 EB026265) and the National Science Foundation (NSF) Award (CBET 1705852). R.K. and C.A.G. would like to acknowledge financial support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR066033 and R21 AR072292) and the National Science Foundation (NSF) Award (CBET 1264848 and 1264832). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agency.
Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - 3D printing
KW - hydrogel scaffolds
KW - mesenchymal stem cells
KW - osteogenic differentiation
KW - stem cell-derived extracellular matrix
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U2 - 10.1002/adhm.201901580
DO - 10.1002/adhm.201901580
M3 - Article
C2 - 32147960
AN - SCOPUS:85081199565
VL - 9
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
SN - 2192-2640
IS - 15
M1 - 1901580
ER -