The control of stem cell morphology and differentiation using three-dimensional printed scaffold architecture
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Biomaterials for 3D Cell Biology Prospective Article
The control of stem cell morphology and differentiation using three-dimensional printed scaffold architecture Murat Guvendiren, Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, Department of Bioengineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102, USA; New Jersey Center for Biomaterials, Rutgers University, Piscataway, NJ 08854, USA Stephanie Fung and Joachim Kohn, New Jersey Center for Biomaterials, Rutgers University, Piscataway, NJ 08854, USA Carmelo De Maria, Francesca Montemurro, and Giovanni Vozzi, Department of Ingegneria dell’Informazione, Research Center “E. Piaggio”, University of Pisa, 56100 Pisa, Italy Address all correspondence to Joachim Kohn at [email protected] (Received 23 May 2017; accepted 10 August 2017)
Abstract In this work, we investigated the interactions of human mesenchymal stem cells (hMSCs) with three-dimensional (3D) printed scaffolds displaying different scaffold architectures. Pressure-assisted microsyringe system was used to fabricate scaffolds with square (SQR), hexagonal (HEX), and octagonal (OCT) architectures defined by various degrees of curvatures. OCT represents the highest degree of curvature followed by HEX, and SQR is composed of linear struts without curvature. Scaffolds were fabricated from poly(L-lactic acid) and poly(tyrosol carbonate). We found that hMSCs attached and spread by taking the shape of the individual struts, exhibiting high aspect ratios (ARs) and mean cell area when cultured on OCT scaffolds as compared with those cultured on HEX and SQR scaffolds. In contrast, cells appeared bulkier with low AR on SQR scaffolds. These significant changes in cell morphology directly correlate with the stem cell lineage commitment, such that 80 ± 1% of the hMSCs grown on OCT scaffolds differentiated into osteogenic lineage, compared with 70 ± 4% and 62 ± 2% of those grown on HEX and SQR scaffolds, respectively. Cells on OCT scaffolds also showed 2.5 times more alkaline phosphatase activity compared with cells on SQR scaffolds. This study demonstrates the importance of scaffold design to direct stem cell differentiation, and aids in the development of novel 3D scaffolds for bone regeneration.
Introduction Stem cells are an important cell source in tissue engineering and regenerative medicine due to their ability to self-renew, migrate, and differentiate into a wide range of tissue-specific cells, including adipogenic (fat), osteogenic (bone), myogenic (muscle), and chondrogenic (cartilage) cells.[1–6] It is now a well-known fact that that stem cells are responsive to their microenvironment.[7] In this regard, chemical, mechanical, and topographical cues present in the microenvironment influence stem cell behavior, including adhesion, proliferation, migration, and differentiation.[7–13] Recent studies have shown that the topography of the substrate alone regulates differentiation of the stem cells.[14–21] An induction media condition comprised soluble biologic cue
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