title: Bioactive membranes for bone regeneration applications: effect of physical and biomolecular signals on mesenchymal stem cell behavior.
abstract: This study focuses on the in vitro characterization of bioactive elastin-like recombinamer (ELR) membranes for bone regeneration applications. Four bioactive ELRs exhibiting epitopes designed to promote mesenchymal stem cell adhesion (RGDS), endothelial cell adhesion (REDV), mineralization (HAP), and both cell adhesion and mineralization (HAP-RGDS) were synthesized using standard recombinant protein techniques. The materials were then used to fabricate ELR membranes incorporating a variety of topographical micropatterns including channels, holes and posts. Primary rat mesenchymal stem cells (rMSCs) were cultured on the different membranes and the effects of biomolecular and physical signals on cell adhesion, morphology, proliferation, and differentiation were evaluated. All results were analyzed using a custom-made MATLAB program for high throughput image analysis. Effects on cell morphology were mostly dependent on surface topography, while cell proliferation and cell differentiation were largely dependent on the biomolecular signaling from the ELR membranes. In particular, osteogenic differentiation (evaluated by staining for the osteoblastic marker osterix) was significantly enhanced on cells cultured on HAP membranes. Remarkably, cells growing on membranes containing the HAP sequence in non-osteogenic differentiation media exhibited significant up-regulation of the osteogenic marker as early as day 5, while those growing on fibronectin-coated glass in osteogenic differentiation media did not. These results are part of our ongoing effort to develop an optimized molecularly designed periosteal graft.
authors.affiliation: Nanotechnology Platform, Parc Científic Barcelona, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Tejeda-Montes
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Smith
authors.forename: Elena
authors.initials: E
authors.lastname: Rebollo
authors.forename: Raúl
authors.initials: R
authors.lastname: Gómez
authors.forename: Matilde
authors.initials: M
authors.lastname: Alonso
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Rodriguez-Cabello
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Engel
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002448:Cell Adhesion; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D048430:Cell Shape / Q000187:drug effects; D004549:Elastin / Q000737:chemistry; D008567:Membranes, Artificial; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D051381:Rats
chemical_list: D001672:Biocompatible Materials; D008567:Membranes, Artificial; D004549:Elastin
keywords: Bioactivity; Elastin-like recombinamers; Membranes; Periosteal grafts; Surface topographies