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      Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates

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          Abstract

          The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals, and plastics, significantly abrogated foreign body reactions and fibrosis when compared to smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5 mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than 5-fold longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved by simply tuning their spherical dimensions.

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          Most cited references52

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          On the mechanisms of biocompatibility.

          The manner in which a mutually acceptable co-existence of biomaterials and tissues is developed and sustained has been the focus of attention in biomaterials science for many years, and forms the foundation of the subject of biocompatibility. There are many ways in which materials and tissues can be brought into contact such that this co-existence may be compromised, and the search for biomaterials that are able to provide for the best performance in devices has been based upon the understanding of all the interactions within biocompatibility phenomena. Our understanding of the mechanisms of biocompatibility has been restricted whilst the focus of attention has been long-term implantable devices. In this paper, over 50 years of experience with such devices is analysed and it is shown that, in the vast majority of circumstances, the sole requirement for biocompatibility in a medical device intended for long-term contact with the tissues of the human body is that the material shall do no harm to those tissues, achieved through chemical and biological inertness. Rarely has an attempt to introduce biological activity into a biomaterial been clinically successful in these applications. This essay then turns its attention to the use of biomaterials in tissue engineering, sophisticated cell, drug and gene delivery systems and applications in biotechnology, and shows that here the need for specific and direct interactions between biomaterials and tissue components has become necessary, and with this a new paradigm for biocompatibility has emerged. It is believed that once the need for this change is recognised, so our understanding of the mechanisms of biocompatibility will markedly improve.
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            Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials.

            A key for long-term survival and function of biomaterials is that they do not elicit a detrimental immune response. As biomaterials can have profound impacts on the host immune response the concept emerged to design biomaterials that are able to trigger desired immunological outcomes and thus support the healing process. However, engineering such biomaterials requires an in-depth understanding of the host inflammatory and wound healing response to implanted materials. One focus of this review is to outline the up-to-date knowledge on immune responses to biomaterials. Understanding the complex interactions of host response and material implants reveals the need for and also the potential of "immunomodulating" biomaterials. Based on this knowledge, we discuss strategies of triggering appropriate immune responses by functional biomaterials and highlight recent approaches of biomaterials that mimic the physiological extracellular matrix and modify cellular immune responses. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Microencapsulated islets as bioartificial endocrine pancreas.

              F. Lim, A Sun (1980)
              Single implantation of microencapsulated islets into rats with streptozotocin-induced diabetes corrected the diabetic state for 2 to 3 weeks. The microencapsulated islets remained morphologically and functionally intact throughout long-term culture studies lasting over 15 weeks.
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                Author and article information

                Journal
                101155473
                30248
                Nat Mater
                Nat Mater
                Nature materials
                1476-1122
                2 May 2015
                18 May 2015
                June 2015
                01 December 2015
                : 14
                : 6
                : 643-651
                Affiliations
                [1 ]David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA, 02139, USA
                [2 ]Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA
                [3 ]Department of Anesthesiology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
                [5 ]Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
                [6 ]Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL
                [7 ]Department for Biomaterials Research, Polymer Institute of the Slovak Academy of Sciences, Dubravska cesta 9, 845 41 Bratislava, Slovakia
                [8 ]Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
                [9 ]Division of Health Science Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA
                [10 ]Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA
                [11 ]Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA
                Author notes
                [# ] dgander@ 123456mit.edu ; Tel.: +1 617 258 6843; fax: +1 617 258 8827
                [*]

                Equal contributing authors

                [4]

                Current address: Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA

                Article
                NIHMS680534
                10.1038/nmat4290
                4477281
                25985456
                e4694924-283a-4857-ae66-f307595142d7
                History
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                Materials science
                Materials science

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