title: The synergistic effects of the RGD density and the microenvironment on the behavior of encapsulated cells: in vitro and in vivo direct comparative study.
abstract: The inclusion of the tripeptide RGD (Arg-Gly-Asp) in otherwise inert biomaterials employed for cell encapsulation has been observed to be an effective strategy to provide the immobilized cells with a more suitable microenvironment. However, some controversial results collected during the last years, especially in vivo, have questioned its effectiveness. Here, we have studied the behavior of C2 C12 myoblasts immobilized in alginate-poly-l-lysine-alginate microcapsules with different densities of RGD. The use of these microcapsules offer the advantage of avoiding native proteins influence permitting to establish direct comparisons between in vitro and in vivo assays. The results suggest that RGD-modified matrices provide higher dynamism, achieving therapeutically more active biosystems not only in vitro, but also in vivo. The highest functionality of the immobilized cells in vitro was obtained with the lowest RGD density. However, higher RGD densities were required in vivo to obtain the same effects observed in vitro. Altogether, these results suggest the lack of in vitro-in vivo correlation when cell behavior is evaluated within different RGD-tailored cell-loaded scaffolds.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country, School of Pharmacy, Vitoria, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
authors.forename: Edorta
authors.initials: E
authors.lastname: Santos
authors.forename: Ane
authors.initials: A
authors.lastname: Garate
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
authors.forename: Gorka
authors.initials: G
authors.lastname: Orive
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Hernández
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002214:Capsules / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D018914:Cells, Immobilized / Q000166:cytology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011107:Polylysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D055153:Stem Cell Niche / Q000187:drug effects*
chemical_list: D000464:Alginates; D002214:Capsules; D009842:Oligopeptides; C051546:alginate-polylysine-alginate; D011107:Polylysine; C047981:arginyl-glycyl-aspartic acid
keywords: RGD; ligand density; microcapsule; microenvironment; scaffold