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      Extracellular Matrix Hydrogels from Decellularized Tissues: Structure and Function

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          Abstract

          Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed.

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          Most cited references88

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          An overview of tissue and whole organ decellularization processes.

          Biologic scaffold materials composed of extracellular matrix (ECM) are typically derived by processes that involve decellularization of tissues or organs. Preservation of the complex composition and three-dimensional ultrastructure of the ECM is highly desirable but it is recognized that all methods of decellularization result in disruption of the architecture and potential loss of surface structure and composition. Physical methods and chemical and biologic agents are used in combination to lyse cells, followed by rinsing to remove cell remnants. Effective decellularization methodology is dictated by factors such as tissue density and organization, geometric and biologic properties desired for the end product, and the targeted clinical application. Tissue decellularization with preservation of ECM integrity and bioactivity can be optimized by making educated decisions regarding the agents and techniques utilized during processing. An overview of decellularization methods, their effect upon resulting ECM structure and composition, and recently described perfusion techniques for whole organ decellularization techniques are presented herein. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix.

            Biologic scaffolds composed of extracellular matrix (ECM) have been used to facilitate the repair and reconstruction of a variety of tissues in clinical and pre-clinical studies. The clinical utility of such scaffolds can be limited by the geometric and mechanical properties of the tissue or organ from which the ECM is harvested. An injectable gel form of ECM could potentially conform to any three-dimensional shape and could be delivered to sites of interest by minimally invasive techniques. The objectives of the present study were to prepare a gel form of ECM harvested from the urinary bladder (urinary bladder matrix or UBM), to characterize the rheological properties of the gel, and finally to evaluate the ability of the gel to support in vitro growth of smooth muscle cells. Following enzymatic solubilization with pepsin, UBM was induced to self-assemble into a gel when brought to physiological conditions. The UBM gel supported the adhesion and growth of rat aortic smooth muscle cells when cultured under static in vitro conditions. The present study showed that an intact form of UBM can be successfully solubilized without purification steps and induced to repolymerize into a gel form of the UBM biologic scaffold material.
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              A hydrogel derived from decellularized dermal extracellular matrix.

              The ECM of mammalian tissues has been used as a scaffold to facilitate the repair and reconstruction of numerous tissues. Such scaffolds are prepared in many forms including sheets, powders, and hydrogels. ECM hydrogels provide advantages such as injectability, the ability to fill an irregularly shaped space, and the inherent bioactivity of native matrix. However, material properties of ECM hydrogels and the effect of these properties upon cell behavior are neither well understood nor controlled. The objective of this study was to prepare and determine the structure, mechanics, and the cell response in vitro and in vivo of ECM hydrogels prepared from decellularized porcine dermis and urinary bladder tissues. Dermal ECM hydrogels were characterized by a more dense fiber architecture and greater mechanical integrity than urinary bladder ECM hydrogels, and showed a dose dependent increase in mechanical properties with ECM concentration. In vitro, dermal ECM hydrogels supported greater C2C12 myoblast fusion, and less fibroblast infiltration and less fibroblast mediated hydrogel contraction than urinary bladder ECM hydrogels. Both hydrogels were rapidly infiltrated by host cells, primarily macrophages, when implanted in a rat abdominal wall defect. Both ECM hydrogels degraded by 35 days in vivo, but UBM hydrogels degraded more quickly, and with greater amounts of myogenesis than dermal ECM. These results show that ECM hydrogel properties can be varied and partially controlled by the scaffold tissue source, and that these properties can markedly affect cell behavior. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                101233144
                32834
                Acta Biomater
                Acta Biomater
                Acta biomaterialia
                1742-7061
                1878-7568
                7 January 2017
                01 December 2016
                February 2017
                01 February 2018
                : 49
                : 1-15
                Affiliations
                [a ]Department of Bioengineering, University of Pittsburgh, 360B CNBIO, 300 Technology Drive, Pittsburgh, PA 15219, USA
                [b ]McGowan Institute for Regenerative Medicine, Suite 300, 450 Technology Drive, University of Pittsburgh, Pittsburgh, PA 15219, USA
                [c ]Department of Chemical Engineering, University of Pittsburgh, 940 Benedum Hall, Pittsburgh, PA 15261, USA
                [d ]School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
                [e ]Department of Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh PA 15213, USA
                Author notes
                Corresponding author: Dr. Stephen F. Badylak, Suite 300, 450 Technology Drive, Pittsburgh, PA 15219, Tel: +1 (412) 235-5253, Fax: +1(412) 235-5256, badylaks@ 123456upmc.edu
                [*]

                These authors contributed equally to this work

                Article
                PMC5253110 PMC5253110 5253110 nihpa839352
                10.1016/j.actbio.2016.11.068
                5253110
                27915024
                49355b65-04a6-45d9-bc6c-d584ee5a2e21
                History
                Categories
                Article

                Extracellular matrix,Tissue engineering,Biomaterial,Regenerative medicine,Injectable,Naturally derived,Decellularization,Hydrogel

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