title: Biomimetic Concealing of PLGA Microspheres in a 3D Scaffold to Prevent Macrophage Uptake.
abstract: Scaffolds functionalized with delivery systems for the release of growth factors is a robust strategy to enhance tissue regeneration. However, after implantation, macrophages infiltrate the scaffold, eventually initiating the degradation and clearance of the delivery systems. Herein, it is hypothesized that fully embedding the poly(d,l-lactide-co-glycolide acid) microspheres (MS) in a highly structured collagen-based scaffold (concealing) can prevent their detection, preserving the integrity of the payload. Confocal laser microscopy reveals that non-embedded MS are easily internalized; when concealed, J774 and bone marrow-derived macrophages (BMDM) cannot detect them. This is further demonstrated by flow cytometry, as a tenfold decrease is found in the number of MS engulfed by the cells, suggesting that collagen can cloak the MS. This correlates with the amount of nitric oxide and tumor necrosis factor-α produced by J774 and BMDM in response to the concealed MS, comparable to that found for non-functionalized collagen scaffolds. Finally, the release kinetics of a reporter protein is preserved in the presence of macrophages, only when MS are concealed. The data provide detailed strategies for fabricating three dimensional (3D) biomimetic scaffolds able to conceal delivery systems and preserve the therapeutic molecules for release.
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Ave., Houston, TX, 77030, USA.|Institute of Science and Technology for Ceramics-CNR (ISTEC-CNR), Via Granarolo 64, 48018, Faenza, RA, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Minardi
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Ave., Houston, TX, 77030, USA.|Department of Life and Environmental Sciences, Università Politecnica delle Marche, 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 Ave., Houston, TX, 77030, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Taraballi
authors.affiliation: Institute of Science and Technology for Ceramics-CNR (ISTEC-CNR), Via Granarolo 64, 48018, Faenza, RA, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Sandri
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Ave., Houston, TX, 77030, USA.
authors.forename: Jonathan O
authors.initials: JO
authors.lastname: Martinez
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Ave., Houston, TX, 77030, USA.
authors.forename: Sebastian T
authors.initials: ST
authors.lastname: Powell
authors.affiliation: Institute of Science and Technology for Ceramics-CNR (ISTEC-CNR), Via Granarolo 64, 48018, Faenza, RA, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Tampieri
authors.affiliation: Department of Regenerative Medicine, Houston Methodist Research Institute (HMRI), 6670 Bertner Ave., Houston, TX, 77030, USA.|Department of Orthopedic Surgery, Houston Methodist Hospital, 6550 Fannin St., 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 Ave., Houston, TX, 77030, USA.
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
mesh_terms: D000327:Adsorption; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry*; D004705:Endocytosis; D017930:Genes, Reporter; D018836:Inflammation Mediators / Q000378:metabolism; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015398:Signal Transduction; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D018836:Inflammation Mediators; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: biomimetic; controlled release; delivery systems; scaffolds; tissue engineering