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      Role of the Complement System in the Response to Orthopedic Biomaterials

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          Abstract

          Various synthetic biomaterials are used to replace lost or damaged bone tissue that, more or less successfully, osseointegrate into the bone environment. Almost all biomaterials used in orthopedic medicine activate the host-immune system to a certain degree. The complement system, which is a crucial arm of innate immunity, is rapidly activated by an implanted foreign material into the human body, and it is intensely studied regarding blood-contacting medical devices. In contrast, much less is known regarding the role of the complement system in response to implanted bone biomaterials. However, given the increasing knowledge of the complement regulation of bone homeostasis, regeneration, and inflammation, complement involvement in the immune response following biomaterial implantation into bone appears very likely. Moreover, bone cells can produce complement factors and are target cells of activated complement. Therefore, new bone formation or bone resorption around the implant area might be greatly influenced by the complement system. This review aims to summarize the current knowledge on biomaterial-mediated complement activation, with a focus on materials primarily used in orthopedic medicine. In addition, methods to modify the interactions between the complement system and bone biomaterials are discussed, which might favor osseointegration and improve the functionality of the device.

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          Most cited references119

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          Fracture healing under healthy and inflammatory conditions.

          Optimal fracture treatment requires knowledge of the complex physiological process of bone healing. The course of bone healing is mainly influenced by fracture fixation stability (biomechanics) and the blood supply to the healing site (revascularization after trauma). The repair process proceeds via a characteristic sequence of events, described as the inflammatory, repair and remodeling phases. An inflammatory reaction involving immune cells and molecular factors is activated immediately in response to tissue damage and is thought to initiate the repair cascade. Immune cells also have a major role in the repair phase, exhibiting important crosstalk with bone cells. After bony bridging of the fragments, a slow remodeling process eventually leads to the reconstitution of the original bone structure. Systemic inflammation, as observed in patients with rheumatoid arthritis, diabetes mellitus, multiple trauma or sepsis, can increase fracture healing time and the rate of complications, including non-unions. In addition, evidence suggests that insufficient biomechanical conditions within the fracture zone can influence early local inflammation and impair bone healing. In this Review, we discuss the main factors that influence fracture healing, with particular emphasis on the role of inflammation.
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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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              Overview of Complement Activation and Regulation

              Summary Complement is an important component of the innate immune system that is crucial for defense from microbial infections and for clearance of immune complexes and injured cells. In normal conditions complement is tightly controlled by a number of fluid-phase and cell surface proteins to avoid injury to autologous tissues. When complement is hyperactivated, as occurs in autoimmune diseases or in subjects with dysfunctional regulatory proteins, it drives a severe inflammatory response in numerous organs. The kidney appears to be particularly vulnerable to complement-mediated inflammatory injury. Injury may derive from deposition of circulating active complement fragments in glomeruli, but complement locally produced and activated in the kidney also may have a role. Many kidney disorders have been linked to abnormal complement activation, including immune-complex–mediated glomerulonephritis and rare genetic kidney diseases, but also tubulointerstitial injury associated with progressive proteinuric diseases or ischemia-reperfusion.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 October 2018
                November 2018
                : 19
                : 11
                : 3367
                Affiliations
                Institute of Orthopedic Research and Biomechanics, Centre for Trauma Research Ulm (ZTF Ulm), University of Ulm, D-89081 Ulm, Germany; yvonne.moedinger@ 123456uni-ulm.de (Y.M.), graciosa.teixeira@ 123456uni-ulm.de (G.Q.T.); cornelia.neidlinger-wilke@ 123456uni-ulm.de (C.N.-W.)
                Author notes
                [* ]Correspondence: anita.ignatius@ 123456uni-ulm.de ; Tel.: +49-731-5005-5301, Fax: +49-731-5005-5302
                Author information
                https://orcid.org/0000-0003-4206-6326
                https://orcid.org/0000-0002-4782-1979
                Article
                ijms-19-03367
                10.3390/ijms19113367
                6274916
                30373272
                af495f56-a0b8-4e0f-897e-da9a33ab067c
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 October 2018
                : 25 October 2018
                Categories
                Review

                Molecular biology
                complement activation,bone,inflammation,biomaterial,implant,orthopedics
                Molecular biology
                complement activation, bone, inflammation, biomaterial, implant, orthopedics

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