Engineered Vascular Tissue Fabricated from Aggregated Smooth Muscle Cells

Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Mass., USA.
Cells Tissues Organs (Impact Factor: 2.14). 06/2011; 194(1):13-24. DOI: 10.1159/000322554
Source: PubMed


The goal of this study was to develop a system to rapidly generate engineered tissue constructs from aggregated cells and cell-derived extracellular matrix (ECM) to enable evaluation of cell-derived tissue structure and function. Rat aortic smooth muscle cells seeded into annular agarose wells (2, 4 or 6 mm inside diameter) aggregated and formed thick tissue rings within 2 weeks of static culture (0.76 mm at 8 days; 0.94 mm at 14 days). Overall, cells appeared healthy and surrounded by ECM comprised of glycosoaminoglycans and collagen, although signs of necrosis were observed near the centers of the thickest rings. Tissue ring strength and stiffness values were superior to those reported for engineered tissue constructs cultured for comparable times. The strength (100-500 kPa) and modulus (0.5-2 MPa) of tissue rings increased with ring size and decreased with culture duration. Finally, tissue rings cultured for 7 days on silicone mandrels fused to form tubular constructs. Ring margins were visible after 7 days, but tubes were cohesive and mechanically stable, and histological examination confirmed fusion between ring subunits. This unique system provides a versatile new tool for optimization and functional assessment of cell-derived tissue, and a new approach to creating tissue-engineered vascular grafts.

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    • "Agarose molds for cell culture were prepared as previously described [35]. Briefly, a polycarbonate sheet (Small Parts Inc., Miramar, FL) was machined to contain annular wells with concentric 2 mm diameter posts surrounded by a 3.75 mm wide trough. "
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    ABSTRACT: There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted into a small animal model for airway defects. The modular, bottom up approach used to grow stem cell-based cartilaginous tubes in this report is a promising platform to engineer complex organs (e.g., trachea), with control over tissue size and geometry, and has the potential to be used to generate autologous tissue implants for human clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 06/2015; 52(1):452-62. DOI:10.1016/j.biomaterials.2015.01.073 · 8.56 Impact Factor
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    • "The cells aggregated around a central post and formed a ring structure. Mechanical properties of the rings were determined at days 8 and 14 post-formation.46 The ultimate tensile strength and ring stiffness were found to be higher in larger rings but decreased as a function of time. "
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    ABSTRACT: There are numerous available biodegradable materials that can be used as scaffolds in regenerative medicine. Currently, there is a huge emphasis on the designing phase of the scaffolds. Materials can be designed to have different properties in order to match the specific application. Modifying scaffolds enhances their bioactivity and improves the regeneration capacity. Modifications of the scaffolds can be later characterized using several tissue engineering tools. In addition to the material, cell source is an important component of the regeneration process. Modified materials must be able to support survival and growth of different cell types. Together, cells and modified biomaterials contribute to the remodeling of the engineered tissue, which affects its performance. This review focuses on the recent advancements in the designs of the scaffolds including the physical and chemical modifications. The last part of this review also discusses designing processes that involve viability of cells.
    05/2014; 6:13-20. DOI:10.4137/BECB.S10961
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    • "Tissue/organ Tissue engineering method Properties attained Translational status Key References Vasculature Self-organization by cell sheet engineering Average burst pressure of 3,490 mm Hg (465 kPa) Phase I clinical studies L'Heureux et al. 1998 (35), Gauvin et al. 2010 (72), Mironov & Kasyanov 2009 (73), Gwyther et al. 2011 (75), McAllister et al. 2009 (77), Haraguchi et al. 2012 (78), L'Heureux et al. 2007 (105) Bioprinting Engineered vascular tube of 900 μm diameter with 300 μm wall thickness In vitro studies Norotte et al. 2009 (41) Articular cartilage Self-assembling process ∼3-mm thick constructs with compressive aggregate modulus of 280 kPa; tensile stiffness at 2 MPa Preclinical animal studies Responte et al. 2012 (4), Hu & Athanasiou 2006 (44), Elder & Athanasiou 2009 (99) Pellet culture ∼1-mm spherical construct In vitro studies Zhang et al. 2004 (13) Aggregate culture ∼500-μm spherical construct In vitro studies Furukawa et al. 2003 (14) Meniscus Self-assembling process Compressive instantaneous modulus of up to 800 kPa and tensile stiffness of up to 3 MPa (tensile modulus in circumferential and radial directions of up to 3 MPa and 1.5 MPa, respectively) Preclinical animal studies Hoben et al. 2007 (45), Aufderheide & Athanasiou 2007 (74), Huey & Athanasiou 2011 (96), Huey & Athanasiou 2011 (97) Eye Self-organization Transparent tissue of 55-μm thickness Preclinical studies Eiraku et al. 2011 (25), Nishida et al. 2004 (36), Proulx et al. 2010 (42), Zhang et al. 2011 (85), Nishida et al. 2004 (110) Tendon and ligament Self-organization Tangent modulus of 15 to 17 MPa Preclinical animal studies Calve et al. 2004 (33), Hairfield-Stein et al. 2007 (63), Huang et al. 2005 (64), Calve et al. 2010 (66) Liver Self-organization Albumin production; prolonged secretion of the oxidation enzyme cytochrome P450; production of α1-antitrypsin In vitro studies Tzanakakis et al. 2001 (59), Koide et al. 1990 (86), Landry et al. 1985 (88), Hansen et al. 1998 (90), Ohashi et al. 2007 (91) Nerve Self-organization Conduction velocities of 12.5 m/s In vitro studies Baltich et al. 2010 (29), Adams et al. 2012 (82) "
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    ABSTRACT: In recent years, the tissue engineering paradigm has shifted to include a new and growing subfield of scaffoldless techniques that generate self-organizing and self-assembling tissues. This review aims to cogently describe this relatively new research area, with special focus on applications toward clinical use and research models. Particular emphasis is placed on providing clear definitions of self-organization and the self-assembling process, as delineated from other scaffoldless techniques in tissue engineering and regenerative medicine. Significantly, during formation, self-organizing and selfassembling tissues display biological processes similar to those that occur in vivo. These processes help lead to the recapitulation of native tissue morphological structure and organization. Notably, functional properties of these engineered tissues, some of which are already in clinical trials, also approach native tissue values. This review endeavors to provide a cohesive summary of work in this field and to highlight the potential of self-organization and the self-assembling process to provide cogent solutions to current intractable problems in tissue engineering. Expected final online publication date for the Annual Review of Biomedical Engineering Volume 15 is July 11, 2013. Please see for revised estimates.
    Annual review of biomedical engineering 05/2013; 15(1). DOI:10.1146/annurev-bioeng-071812-152423 · 14.21 Impact Factor
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