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Evaluation of Fibrin-Based Interpenetrating Polymer Networks as Potential Biomaterials for Tissue Engineering

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      Abstract

      Interpenetrating polymer networks (IPNs) have gained great attention for a number of biomedical applications due to their improved properties compared to individual components alone. In this study, we investigated the capacity of newly-developed naturally-derived IPNs as potential biomaterials for tissue engineering. These IPNs combine the biologic properties of a fibrous fibrin network polymerized at the nanoscale and the mechanical stability of polyethylene oxide (PEO). First, we assessed their cytotoxicity in vitro on L929 fibroblasts. We further evaluated their biocompatibility ex vivo with a chick embryo organotypic culture model. Subcutaneous implantations of the matrices were subsequently conducted on nude mice to investigate their biocompatibility in vivo. Our preliminary data highlighted that our biomaterials were non-cytotoxic (viability above 90%). The organotypic culture showed that the IPN matrices induced higher cell adhesion (across all the explanted organ tissues) and migration (skin, intestine) than the control groups, suggesting the advantages of using a biomimetic, yet mechanically-reinforced IPN-based matrix. We observed no major inflammatory response up to 12 weeks post implantation. All together, these data suggest that these fibrin-based IPNs are promising biomaterials for tissue engineering.

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      The foreign body reaction composed of macrophages and foreign body giant cells is the end-stage response of the inflammatory and wound healing responses following implantation of a medical device, prosthesis, or biomaterial. A brief, focused overview of events leading to the foreign body reaction is presented. The major focus of this review is on factors that modulate the interaction of macrophages and foreign body giant cells on synthetic surfaces where the chemical, physical, and morphological characteristics of the synthetic surface are considered to play a role in modulating cellular events. These events in the foreign body reaction include protein adsorption, monocyte/macrophage adhesion, macrophage fusion to form foreign body giant cells, consequences of the foreign body response on biomaterials, and cross-talk between macrophages/foreign body giant cells and inflammatory/wound healing cells. Biomaterial surface properties play an important role in modulating the foreign body reaction in the first two to four weeks following implantation of a medical device, even though the foreign body reaction at the tissue/material interface is present for the in vivo lifetime of the medical device. An understanding of the foreign body reaction is important as the foreign body reaction may impact the biocompatibility (safety) of the medical device, prosthesis, or implanted biomaterial and may significantly impact short- and long-term tissue responses with tissue-engineered constructs containing proteins, cells, and other biological components for use in tissue engineering and regenerative medicine. Our perspective has been on the inflammatory and wound healing response to implanted materials, devices, and tissue-engineered constructs. The incorporation of biological components of allogeneic or xenogeneic origin as well as stem cells into tissue-engineered or regenerative approaches opens up a myriad of other challenges. An in depth understanding of how the immune system interacts with these cells and how biomaterials or tissue-engineered constructs influence these interactions may prove pivotal to the safety, biocompatibility, and function of the device or system under consideration.
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        A paradigm shift is taking place in medicine from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous material scaffolds integrated with biological cells or molecules to regenerate tissues. This new paradigm requires scaffolds that balance temporary mechanical function with mass transport to aid biological delivery and tissue regeneration. Little is known quantitatively about this balance as early scaffolds were not fabricated with precise porous architecture. Recent advances in both computational topology design (CTD) and solid free-form fabrication (SFF) have made it possible to create scaffolds with controlled architecture. This paper reviews the integration of CTD with SFF to build designer tissue-engineering scaffolds. It also details the mechanical properties and tissue regeneration achieved using designer scaffolds. Finally, future directions are suggested for using designer scaffolds with in vivo experimentation to optimize tissue-engineering treatments, and coupling designer scaffolds with cell printing to create designer material/biofactor hybrids.
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          Biodegradable polymers and bioactive ceramics are being combined in a variety of composite materials for tissue engineering scaffolds. Materials and fabrication routes for three-dimensional (3D) scaffolds with interconnected high porosities suitable for bone tissue engineering are reviewed. Different polymer and ceramic compositions applied and their impact on biodegradability and bioactivity of the scaffolds are discussed, including in vitro and in vivo assessments. The mechanical properties of today's available porous scaffolds are analyzed in detail, revealing insufficient elastic stiffness and compressive strength compared to human bone. Further challenges in scaffold fabrication for tissue engineering such as biomolecules incorporation, surface functionalization and 3D scaffold characterization are discussed, giving possible solution strategies. Stem cell incorporation into scaffolds as a future trend is addressed shortly, highlighting the immense potential for creating next-generation synthetic/living composite biomaterials that feature high adaptiveness to the biological environment.
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            Author and article information

            Affiliations
            [1 ]Laboratoire de BioMécanique et de BioIngénierie (BMBI) UMR CNRS 7388, Sorbonne Universités, Université de Technologie of Compiègne (UTC), 60200 Compiègne, France; olfat.gsib@ 123456gmail.com (O.G.); jlcalanq@ 123456gmail.com (J.-L.D.)
            [2 ]Equipe de Recherche sur les Relations Matrice Extracellulaire Cellules (Errmece), Institut des Matériaux, Université de Cergy-Pontoise, 95000 Cergy-Pontoise, France; mathieu.goczkowski@ 123456gmail.com (M.G.); mdeneufchatel@ 123456gmail.com (M.D.); veronique.larreta-garde@ 123456u-cergy.fr (V.L.-G.)
            [3 ]Laboratoire de Physicochimie des Polymères et des Interfaces (LPPI), Institut des Matériaux, Université de Cergy-Pontoise, 95000 Cergy-Pontoise, France; odile.fichet@ 123456u-cergy.fr
            [4 ]School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
            [5 ]Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02215, USA
            Author notes
            [* ]Correspondence: s.bencherif@ 123456northeastern.edu (S.A.B.); christophe.egles@ 123456utc.fr (C.E.); Tel.: +1-617-373-7103 (S.A.B.); +33-(0)3-44-23-44-22 (C.E.)
            Journal
            Nanomaterials (Basel)
            Nanomaterials (Basel)
            nanomaterials
            Nanomaterials
            MDPI
            2079-4991
            10 December 2017
            December 2017
            : 7
            : 12
            29232876
            5746926
            10.3390/nano7120436
            nanomaterials-07-00436
            © 2017 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/).

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