title: IL-4 Release from a Biomimetic Scaffold for the Temporally Controlled Modulation of Macrophage Response.
abstract: The interaction of immune cells with biomaterials has been identified as a possible predictor of either the success or the failure of the implant. Among immune cells, macrophages have been found to contribute to both of these possible scenarios, based on their polarization profile. This proof-of-concept study aimed to investigate if it was possible to affect the response of macrophages to biomaterials, by the release of anti-inflammatory mediators. Towards this end, a collagen scaffold, integrated with poly(lactic-co-glycolic acid)-multistage silicon particles (MSV) composite microspheres (PLGA-MSV) releasing IL-4 was developed (PLGA-MSV/IL-4). Macrophages' response to the scaffold was evaluated, both in vitro with rat bone-marrow derived macrophages, and in vivo in a rat subcutaneous pouch model. In vitro experiments revealed an overexpression of anti-inflammatory associated genes (Il-10, Mrc1, Arg1) at as soon as 48 h. The analysis of the cells that infiltrated the scaffold, revealed a prevalence of CD206(+) macrophages at 24 h. Our strategy demonstrated that it is possible to tune the in vivo early response to biomaterials by the release of an anti-inflammatory cytokine, and that could contribute to accelerate the resolution of the inflammatory phase, benefiting a vast range of tissue engineering applications.
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Minardi
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA.|Department of Life and Environmental Sciences, Università Politecnica delle Marche, via Brecce Bianche, 60131, Ancona, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Corradetti
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Taraballi
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA.
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Byun
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabrera
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA.
authors.forename: Xeuwu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Orthopaedics, Houston Methodist Hospital (HMH), 6550 Fannin St, Houston, TX, 77030, USA.|The Surgical Advanced Technology Laboratory, Houston Methodist Research Institute (HMRI), 6670 Bertner Ave, Houston, TX, 77030, USA.
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Weiner
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Avenue, Houston, TX, 77030, USA. etasciotti@houstonmethodist.org.|The Surgical Advanced Technology Laboratory, Houston Methodist Research Institute (HMRI), 6670 Bertner Ave, Houston, TX, 77030, USA. etasciotti@houstonmethodist.org.
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
mesh_terms: D000818:Animals; D001119:Arginase / Q000096:biosynthesis; D040761:Biomimetic Materials / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D011971:Receptors, Immunologic / Q000096:biosynthesis; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D011971:Receptors, Immunologic; D016753:Interleukin-10; D015847:Interleukin-4; D001119:Arginase
keywords: Biomimetic; Controlled release; IL-4; Inflammation; Scaffolds