Decorin-containing collagen hydrogels as dimensionally stable scaffolds to study the effects of compressive mechanical l
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Biomaterials for 3D Cell Biology Research Letter
Decorin-containing collagen hydrogels as dimensionally stable scaffolds to study the effects of compressive mechanical loading on angiogenesis Marissa A. Ruehle, Georgia Institute of Technology, Petit Institute for Bioengineering and Biosciences, Atlanta, GA, USA; Emory University, Atlanta, GA, USA Laxminarayanan Krishnan, Georgia Institute of Technology, Petit Institute for Bioengineering and Biosciences, Atlanta, GA, USA Steven A. LaBelle, University of Utah, Salt Lake City, UT, USA Nick J. Willett, Georgia Institute of Technology, Petit Institute for Bioengineering and Biosciences, Atlanta, GA, USA; Emory University, Atlanta, GA, USA; Atlanta Veteran’s Affairs Medical Center, Decatur, GA, USA Jeffrey A. Weiss, University of Utah, Salt Lake City, UT, USA Robert E. Guldberg, Georgia Institute of Technology, Petit Institute for Bioengineering and Biosciences, Atlanta, GA, USA Address all correspondence to R. E. Guldberg at [email protected] (Received 15 May 2017; accepted 5 July 2017)
Abstract Angiogenesis is a critical component during wound healing, and the process is sensitive to mechanical stimuli. Current in vitro culture environments used to investigate three-dimensional microvascular growth often lack dimensional stability and the ability to withstand compression. We investigated the ability of decorin (DCN), a proteoglycan known to modulate collagen fibrillogenesis, incorporated into a collagen hydrogel to increase construct dimensional stability while maintaining vascular growth. DCN did not affect microvascular growth parameters, while increasing the compressive modulus of collagen gels and significantly reducing the contraction of 3% collagen gels after 16 days in culture.
Introduction Vascular growth and remodeling are processes that are highly sensitive to mechanical cues; however, much of the existing research in this field has focused on luminal mechanics related to fluid flow (i.e., fluid shear and cyclic stretch) rather than abluminal stimulation of the vessel network itself.[1] Abluminal forces are particularly relevant to load-bearing tissues such as bone, and it is well established that angiogenesis and osteogenesis are intimately linked in both development and healing.[2,3] Additionally, a previous study in vivo showed that functional loading has a potent time-dependent influence on vascular growth during segmental bone defect healing; early loading impaired vessel growth, whereas delayed loading enhanced vascular growth.[4] Well-controlled in vitro studies are needed to better understand the mechanical cues associated with vascular growth and inhibition. Microvascular fragments (MVF) are multicellular segments of vasculature that can sprout and form networks in vitro.[5] In combination with an appropriate three-dimensional (3D) substrate, MVFs allow for interactions between multiple cell types and between cells and their matrix, thereby better representing the complex in vivo processes of angiogenesis than models utilizing single cells or
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