Scaffold Architecture and Matrix Strain Modulate Mesenchymal Cell and Microvascular Growth and Development in a Time Dep
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Cellular and Molecular Bioengineering ( 2020) https://doi.org/10.1007/s12195-020-00648-7
2020 CMBE Young Innovators issue
Scaffold Architecture and Matrix Strain Modulate Mesenchymal Cell and Microvascular Growth and Development in a Time Dependent Manner GENNIFER CHIOU,1 ELYSA JUI,1 ALLISON C. RHEA,1 APARNA GORTHI,2 SOLALEH MIAR,1 FRANCISCA M. ACOSTA,1 CYNTHIA PEREZ,1 YASIR SUHAIL,3 KSHITIZ,3,4 YIDONG CHEN,2 JOO L. ONG,1 RENA BIZIOS,1 CHRISTOPHER RATHBONE,1 and TEJA GUDA 1 1
Department of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, San Antonio, TX 78249, USA; 2Greehey Children’s Cancer Research Institute, University of Texas Health at San Antonio, San Antonio, TX 78229, USA; 3Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA; and 4Cancer Systems Biology at Yale, Yale University, West Haven, CT 06516, USA (Received 15 February 2020; accepted 11 August 2020) Associate Editor Shelly Peyton oversaw the review of this article.
Abstract Background—Volumetric tissue-engineered constructs are limited in development due to the dependence on wellformed vascular networks. Scaffold pore size and the mechanical properties of the matrix dictates cell attachment, proliferation and successive tissue morphogenesis. We hypothesize scaffold pore architecture also controls stromal-vessel interactions during morphogenesis. Methods—The interaction between mesenchymal stem cells (MSCs) seeded on hydroxyapatite scaffolds of 450, 340, and 250 lm pores and microvascular fragments (MVFs) seeded within 20 mg/mL fibrin hydrogels that were cast into the cellseeded scaffolds, was assessed in vitro over 21 days and compared to the fibrin hydrogels without scaffold but containing both MSCs and MVFs. mRNA sequencing was performed across all groups and a computational mechanics model was developed to validate architecture effects on predicting vascularization driven by stiffer matrix behavior at scaffold surfaces compared to the pore interior. Results—Lectin staining of decalcified scaffolds showed continued vessel growth, branching and network formation at 14 days. The fibrin gel provides no resistance to spread-out capillary networks formation, with greater vessel loops within the 450 lm pores and vessels bridging across 250 lm pores. Vessel growth in the scaffolds was observed to be stimulated by hypoxia and successive angiogenic signaling. Fibrin gels showed linear fold increase in VEGF expression and no change in BMP2. Within scaffolds, there was multiple fold increase in VEGF between days 7 and 14 and early multiple fold increases in BMP2 between days 3 and 7, relative to fibrin. There was evidence of yap/taz based
Address correspondence to Teja Guda, Department of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, San Antonio, TX 78249, USA. Electronic mail: teja. [email protected]
hippo signaling and mechanotransduction in the scaffold groups. The vessel growth models determined by computational modeling matched th
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