Stiffening of Human Mesenchymal Stem Cell Spheroid Microenvironments Induced by Incorporation of Gelatin Microparticles

• Type of Material: Article
• Authors: Priya R. Baraniak, Georgia Institute of Technology; Marissa T. Cooke, Georgia Institute of Technology; Rabbia Saeed, Georgia Institute of Technology; Melissa A. Kinney, Georgia Institute of Technology; Krista M. Fridley, Georgia Institute of Technology; Todd McDevitt, Emory University
• Language: English
• Date: 2012-07-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jmbbm.2012.02.018
• Title of Journal or Parent Work: Journal of the Mechanical Behavior of Biomedical Materials
• ISSN: 1751-6161
• Volume: 11
• Start Page: 63
• End Page: 71
• Grant/Funding Information: This work was supported by funding from the NIH (R01 GM088291, R01 EB010061) and NSF (CBET 0939511).
• Keywords: Materials Science, Biomaterials; Materials Science; Stem cells; STROMAL CELLS; SUBSTRATE; Engineering, Biomedical; TISSUE REGENERATION; Tissue engineering; TUMOR SPHEROIDS; MECHANICAL REGULATION; Engineering; Polymers; Science & Technology; Mesenchymal stem cells; ELASTICITY; DIFFERENTIATION; GENERATION; BONE-MARROW; Technology; Microparticles; STIFFNESS; Biomaterials
• Research Categories: Engineering, Biomedical

Abstract

Culturing multipotent adult mesenchymal stem cells as 3D aggregates augments their differentiation potential and paracrine activity. One caveat of stem cell spheroids, though, can be the limited diffusional transport barriers posed by the inherent 3D structure of the multicellular aggregates. In order to circumvent such limitations, polymeric microparticles have been incorporated into stem cell aggregates as a means to locally control the biochemical and physical properties of the 3D microenvironment. However, the introduction of biomaterials to the 3D stem cell microenvironment could alter the mechanical forces sensed by cells within aggregates, which in turn could impact various cell behaviors and overall spheroid mechanics. Therefore, the objective of this study was to determine the acute effects of biomaterial incorporation within mesenchymal stem cell spheroids on aggregate structure and mechanical properties. The results of this study demonstrate that although gelatin microparticle incorporation results in similar multi-cellular organization within human mesenchymal stem cell spheroids, the introduction of gelatin materials significantly impacts spheroid mechanical properties. The marked differences in spheroid mechanics induced by microparticle incorporation may hold major implications for . in vitro directed differentiation strategies and offer a novel route to engineer the mechanical properties of tissue constructs . ex vivo.