title: Delivery strategies to control inflammatory response: Modulating M1-M2 polarization in tissue engineering applications.
abstract: Macrophages are key players in many physiological scenarios including tissue homeostasis. In response to injury, typically the balance between macrophage sub-populations shifts from an M1 phenotype (pro-inflammatory) to an M2 phenotype (anti-inflammatory). In tissue engineering scenarios, after implantation of any device, it is desirable to exercise control on this M1-M2 progression and to ensure a timely and smooth transition from the inflammatory to the healing stage. In this review, we briefly introduce the current state of knowledge regarding macrophage function and nomenclature. Next, we discuss the use of controlled release strategies to tune the balance between the M1 and M2 phenotypes in the context of tissue engineering applications. We discuss recent literature related to the release of anti-inflammatory molecules (including nucleic acids) and the sequential release of cytokines to promote a timely M1-M2 shift. In addition, we describe the use of macrophages as controlled release agents upon stimulation by physical and/or mechanical cues provided by scaffolds. Moreover, we discuss current and future applications of "smart" implantable scaffolds capable of controlling the cascade of biochemical events related to healing and vascularization. Finally, we provide our opinion on the current challenges and the future research directions to improve our understanding of the M1-M2 macrophage balance and properly exploit it in tissue engineering and regenerative medicine applications.
authors.affiliation: Biomaterials Innovation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Microsystems Technologies Laboratories, Massachusetts Institute of Technology, Cambridge, MA, USA; Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Monterrey, Nuevo León, México.
authors.forename: Mario Moisés
authors.initials: MM
authors.lastname: Alvarez
authors.affiliation: Biomaterials Innovation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; School of Chemical Engineering and Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Biomaterials Innovation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Microsystems Technologies Laboratories, Massachusetts Institute of Technology, Cambridge, MA, USA; Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Monterrey, Nuevo León, México.
authors.forename: Grissel
authors.initials: G
authors.lastname: Trujillo-de Santiago
authors.affiliation: Biomaterials Innovation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Cha
authors.affiliation: Biomaterials Innovation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Ajaykumar
authors.initials: A
authors.lastname: Vishwakarma
authors.affiliation: Division of Immunology, School of Life Sciences, Faculty of Medicine and Health Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Amir M
authors.initials: AM
authors.lastname: Ghaemmaghami
authors.affiliation: Biomaterials Innovation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Microsystems Technologies Laboratories, Massachusetts Institute of Technology, Cambridge, MA, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA; Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul, Republic of Korea; Department of Physics, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: alik@rics.bwh.harvard.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry; D016764:Cell Polarity / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D016207:Cytokines; D003692:Delayed-Action Preparations
keywords: Anti-inflammatory; Controlled release; Inflammation; M1 and M2; Macrophages; Tissue engineering