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      Decellularization Strategies for Regenerative Medicine: From Processing Techniques to Applications

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      BioMed Research International
      Hindawi

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          Abstract

          As the gap between donors and patients in need of an organ transplant continues to widen, research in regenerative medicine seeks to provide alternative strategies for treatment. One of the most promising techniques for tissue and organ regeneration is decellularization, in which the extracellular matrix (ECM) is isolated from its native cells and genetic material in order to produce a natural scaffold. The ECM, which ideally retains its inherent structural, biochemical, and biomechanical cues, can then be recellularized to produce a functional tissue or organ. While decellularization can be accomplished using chemical and enzymatic, physical, or combinative methods, each strategy has both benefits and drawbacks. The focus of this review is to compare the advantages and disadvantages of these methods in terms of their ability to retain desired ECM characteristics for particular tissues and organs. Additionally, a few applications of constructs engineered using decellularized cell sheets, tissues, and whole organs are discussed.

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          Most cited references75

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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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            The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder.

            A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.
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              Stem cell fate dictated solely by altered nanotube dimension.

              Two important goals in stem cell research are to control the cell proliferation without differentiation and to direct the differentiation into a specific cell lineage when desired. Here, we demonstrate such paths by controlling only the nanotopography of culture substrates. Altering the dimensions of nanotubular-shaped titanium oxide surface structures independently allowed either augmented human mesenchymal stem cell (hMSC) adhesion or a specific differentiation of hMSCs into osteoblasts by using only the geometric cues, absent of osteogenic inducing media. hMSC behavior in response to defined nanotube sizes revealed a very dramatic change in hMSC behavior in a relatively narrow range of nanotube dimensions. Small (approximately 30-nm diameter) nanotubes promoted adhesion without noticeable differentiation, whereas larger (approximately 70- to 100-nm diameter) nanotubes elicited a dramatic stem cell elongation (approximately 10-fold increased), which induced cytoskeletal stress and selective differentiation into osteoblast-like cells, offering a promising nanotechnology-based route for unique orthopedics-related hMSC treatments.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2017
                30 April 2017
                : 2017
                : 9831534
                Affiliations
                Department of Chemical and Biomedical Engineering, West Virginia University, Morgantown, WV 26506, USA
                Author notes

                Academic Editor: Costantino Del Gaudio

                Author information
                http://orcid.org/0000-0003-4305-8029
                Article
                10.1155/2017/9831534
                5429943
                28540307
                e8200610-29ef-41c5-bce0-ad7d784c55e7
                Copyright © 2017 Anna Gilpin and Yong Yang.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 January 2017
                : 15 March 2017
                : 12 April 2017
                Funding
                Funded by: National Institute of Health
                Award ID: R15GM122953
                Funded by: NASA
                Categories
                Review Article

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