Immunomodulatory Biomaterials and Regenerative Immunology
2016; Future Science Ltd; Volume: 2; Issue: 4 Linguagem: Inglês
10.4155/fsoa-2016-0060
ISSN2056-5623
Autores Tópico(s)Graphene and Nanomaterials Applications
ResumoFuture Science OAVol. 2, No. 4 EditorialOpen AccessImmunomodulatory biomaterials and regenerative immunologyNihal Engin VranaNihal Engin Vrana*Author for correspondence: E-mail Address: e.vrana@protipmedical.com Protip Medical, 8 Place de l'Hopital, 67000 Strasbourg, France INSERM UMR 1121, 11 Rue Humann, 67000 Strasbourg, FrancePublished Online:29 Sep 2016https://doi.org/10.4155/fsoa-2016-0060AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit Keywords: biomaterialsimmunologyimmunomodulationmacrophagesregenerative medicineFirst draft submitted: 23 August 2016; Accepted for publication: 24 August 2016; Published online: 29 September 2016Organ damage and loss remain important clinical problems, where the current gold standard is transplantation. One of the main problems with transplants, even when they are successful, is the need to use immunosuppressants (IS) for preventing acute rejection. The use of IS entails several side effects such as increased risk of tumor formation, higher susceptibility to infections and IS-related toxicity. Even though in certain cases, such as liver transplants, weaning off the IS has been achieved [1], in many transplant scenarios the use of IS is indispensable. This aspect was one of the initial promises of tissue engineering as the use of autologous cells and biocompatible biomaterials would render the use of IS unnecessary.In order to prevent rejection, a strict donor–recipient match is necessary and although a high level of efficacy has been achieved with transplant recipients (>95% 1-year survival rate), the increasing number of patients on the donor waiting lists without a corresponding increase in the number of donated organs demonstrates the need for an alternative source of replacement organs. Moreover, beyond the donor–recipient matching, the level of long-term success will be dependent on the demographic data pertaining to donor and the donor's medical history together with the reason of death. For example, donors for whom the reason of death was cerebrovascular disease have been shown to be more prone to induce rejection [2]. Furthermore, even though the survival rates are high, the deterioration of the transplant is not completely evitable. T-cell mediated scarring of the allograft or antibody-mediated processes will still be active.Immunomodulation methods beyond systemic immunosuppression have been under development. Such technologies include donor regulatory T-cell therapy for promoting tolerance, antibody-based approaches for suppression of alloreactive T cells, allogenic antigen presentation methods during autologous cell debris scavenging to induce tolerance or low-dose IL-2 application for increasing host-regulatory T-cell numbers [3,4]. The use of biomaterials as immunomodulatory agents started with the encapsulation of allogenic Langerhans islets for treatment of diabetes using materials with low immunogenicity such as alginate. This provides an active barrier between the immune cells and antibodies of the host, and the metabolically active implanted allogenic cells. In a similar vein, biomaterial-based controlled delivery systems can achieve local control of immune response, hence circumventing most of the side effects of systemic immunomodulation [5].In the context of regenerative medicine, these methods can provide means to utilize allogenic cell sources rather than autologous cells for patients with congenital diseases or with compromised cell populations. Moreover, coupling of immunomodulatory agents directly to biomaterials to render them immunomodulatory biomaterials [6] will help the development of highly remodelable scaffolds in vivo with regenerative properties beyond the inherent immunomodulatory activities of systems such as decellularized tissues [7].Tissue engineering and regenerative medicine have come a long way in solving problems pertaining to organ/tissue loss and damage. In the last 10 years, more and more cases of clinical implementation of tissue engineering have been published with short- and long-term successes [8]. Moreover, the advances in tissue engineering have also led to development of complex 3D in vitro artificial tissue and organ systems that are being actively improved for replacement of animal experiments and also as more relevant models for drug and pharmacological tests [9]. These successes give hope for design and implementation of more complex tissues. For development of fully functional engineered tissues incorporation of immune cells or immunomodulatory elements might have significant benefits [10].Even though tissues can be defined in a manner that emphasizes their specific function, barring certain exceptions, the presence of the components of three other systems of the body (namely, innervations, incoming and outgoing vasculature and resident immune cells) are common for all tissues. Because of the complexity of achieving a fully developed tissue, tissue engineering research has generally focused on the production of tissue-like structures containing the main functional cells of a tissue (such as chondrocytes for cartilage or osteoblasts for bone) where certain tissue-specific characteristics are taken as a marker of tissue maturation. Even though successful differentiation and microtissue formation in these settings can be achieved in vitro, for actual clinically relevant size defects, the necessity of integration with the host vasculature has been realized. In order to facilitate the integration, several different methodologies have been devised such as sacrificial microfluidic channels in scaffolds for improving capillary in-growth; addition of chemoattractants and growth factors to induce angiogenesis toward the implanted artificial tissue; and incorporation of vascular endothelial cells for prevascularization [11]. Co-culture of endothelial cells with other cell types generally induced not only capillary sprouting but also a synergistic interaction between the two cell types that contribute to the maturation of the engineered tissue.The next in line in the sophistication of engineered tissues can be the inclusion of the immune system component. Nearly all tissues have resident macrophage populations which has been shown to be an important factor in tissue homeostasis and healing upon injury [12]. Recently, there has been a growing focus on the control over innate immune response in the microenvironment of implanted materials particularly through well-established macrophage polarization pathways that have been shown to have a crucial role in vascularization of implanted scaffolds [13]. Immunoassisted tissue engineering approaches can harness the ability of innate immune cells to resolve inflammation and promote regeneration and healing. This can be achieved by exploiting the phenotypic plasticity of immune cells either via controlled delivery of specific phenotype inducing cytokines [14] or direct co-delivery of phenotype controlled immune cells together with the cells relevant to the target organ function.A new focus on establishing a cross-talk with the host immune system, rather than trying to evade it, could pave the way for more functional and fast-integrating artificial tissues. Concomitant use of new developments in temporal control of multiple growth factor/cytokine delivery; advanced bottom-up assembly methods of engineered tissues such as robotic assembly [15]; use of bioactive miRNAs within scaffolds; and micro/nanoscale topographical and chemical control of scaffold features [16] for inducing anti- or proinflammatory immune cell phenotypes would provide the tools for engineering multicellular organs and establishing in vitro organoids that faithfully model physiological conditions with immune system components. These efforts would bring forth the aspects of 'regenerative immunology' in regenerative medicine.Financial & competing interests disclosureThe author declares receiving funding from EU FP7 Framework programme (IMMODGEL grant no. 602694) for development of immunomodulatory systems to control adverse immune reactions. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.Open accessThis work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Papers of special note have been highlighted as: • of interestReferences1 Orlando G, Wood KJ, Soker S, Stratta RJ. How regenerative medicine may contribute to the achievement of an immunosuppression-free state. Transplantation 92(8), e36–e38 (2011).Crossref, Medline, Google Scholar2 Rogers J, Katari R, Gifford S et al. Kidney transplantation, bioengineering and regeneration: an originally immunology-based discipline destined to transition towards ad hoc organ manufacturing and repair. Expert Rev. Clin. 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Part B Rev. 15(3), 353–370 (2009).Crossref, Medline, CAS, Google Scholar12 Davies LC, Jenkins SJ, Allen JE, Taylor PR. Tissue-resident macrophages. Nat. Immunol. 14(10), 986–995 (2013). • Review on the structure and function of resident macrophages and their specific properties in different tissues/organs.Crossref, Medline, CAS, Google Scholar13 Spiller KL, Anfang RR, Spiller KJ et al. The role of macrophage phenotype in vascularization of tissue engineering scaffolds. Biomaterials 35(15), 4477–4488 (2014).Crossref, Medline, CAS, Google Scholar14 Spiller KL, Nassiri S, Witherel CE et al. Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds. Biomaterials 37, 194–207 (2015).Crossref, Medline, CAS, Google Scholar15 Tasoglu S, Diller E, Guven S, Sitti M, Demirci U. Untethered micro-robotic coding of three-dimensional material composition. Nat. 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Immunobiology doi:http://dx.doi.org/10.1016/j.imbio.2016.06.010 (2016) (Epub ahead of print).Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited ByThe role of biomaterials and scaffolds in immune responses in regenerative medicine: macrophage phenotype modulation by biomaterial properties and scaffold architectures1 January 2021 | Biomaterials Science, Vol. 9, No. 24Platelet rich plasma concentration improves biologic mesh incorporation and decreases multinucleated giant cells in a dose dependent fashion1 October 2021 | Journal of Tissue Engineering and Regenerative Medicine, Vol. 15, No. 11Personalization of medical device interfaces: decreasing implant-related complications by modular coatings and immunoprofilingNihal Engin Vrana, Kaia Palm & Philippe Lavalle30 July 2020 | Future Science OA, Vol. 6, No. 8Cell Encapsulation Systems Toward Modular Tissue Regeneration: From Immunoisolation to Multifunctional Devices5 February 2020 | Advanced Functional Materials, Vol. 30, No. 26Emerging Nano/Micro-Structured Degradable Polymeric Meshes for Pelvic Floor Reconstruction5 June 2020 | Nanomaterials, Vol. 10, No. 6Immunomodulatory properties of photopolymerizable fucoidan and carrageenansCarbohydrate Polymers, Vol. 230Mesenchymal stem cell-based bioengineered constructs: foreign body response, cross-talk with macrophages and impact of biomaterial design strategies for pelvic floor disorders14 June 2019 | Interface Focus, Vol. 9, No. 4Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation20 August 2018 | Frontiers in Bioengineering and Biotechnology, Vol. 6Engineering Pro-Regenerative Hydrogels for Scarless Wound Healing16 April 2018 | Advanced Healthcare Materials, Vol. 7, No. 14Incorporation of resident macrophages in engineered tissues: Multiple cell type response to microenvironment controlled macrophage‐laden gelatine hydrogels28 July 2017 | Journal of Tissue Engineering and Regenerative Medicine, Vol. 12, No. 2Biologically synthesized metal nanoparticles: recent advancement and future perspectives in cancer theranosticsSudip Mukherjee & Chitta Ranjan Patra26 May 2017 | Future Science OA, Vol. 3, No. 3Analysis of cell behavior on micropatterned surfaces by image processing algorithms Vol. 2, No. 4 Follow us on social media for the latest updates Metrics History Published online 29 September 2016 Published in print December 2016 Information© Nihal Engin VranaKeywordsbiomaterialsimmunologyimmunomodulationmacrophagesregenerative medicineFinancial & competing interests disclosureThe author declares receiving funding from EU FP7 Framework programme (IMMODGEL grant no. 602694) for development of immunomodulatory systems to control adverse immune reactions. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.Open accessThis work is licensed under the Creative Commons Attribution 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/PDF download
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