title: A nanostructured bacterial bioscaffold for the sustained bottom-up delivery of protein drugs.
abstract: OBJECTIVE
  Bacterial inclusion bodies (IBs) are protein-based, amyloidal nanomaterials that mechanically stimulate mammalian cell proliferation upon surface decoration. However, their biological performance as potentially functional scaffolds in mammalian cell culture still needs to be explored.
  
  
  METHODS
  Using fluorescent proteins, we demonstrate significant membrane penetration of surface-attached IBs and a corresponding intracellular bioavailability of the protein material.
  
  
  RESULTS
  When IBs are formed by protein drugs, such as the intracellular acting human chaperone Hsp70 or the extracellular/intracellular acting human FGF-2, IB components intervene on top-growing cells, namely by rescuing them from chemically induced apoptosis or by stimulating cell division under serum starvation, respectively. Protein release from IBs seems to mechanistically mimic the sustained secretion of protein hormones from amyloid-like secretory granules in higher organisms.
  
  
  CONCLUSIONS
  We propose bacterial IBs as biomimetic nanostructured scaffolds (bioscaffolds) suitable for tissue engineering that, while acting as adhesive materials, partially disintegrate for the slow release of their biologically active building blocks. The bottom-up delivery of protein drugs mediated by bioscaffolds offers a highly promising platform for emerging applications in regenerative medicine.
authors: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain and Department de Genètica i de MicroBiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain and CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, 08193 Barcelona, Spain.
authors: Joaquin
authors: J
authors: Seras-Franzoso
authors: Karl
authors: K
authors: Peebo
authors: José
authors: J
authors: Luis Corchero
authors: Penelope M
authors: PM
authors: Tsimbouri
authors: Ugutz
authors: U
authors: Unzueta
authors: Ursula
authors: U
authors: Rinas
authors: Matthew J
authors: MJ
authors: Dalby
authors: Esther
authors: E
authors: Vazquez
authors: Elena
authors: E
authors: García-Fruitós
authors: Antonio
authors: A
authors: Villaverde
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D004926:Escherichia coli / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D002479:Inclusion Bodies; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D023822:Tissue Engineering
chemical_list: D018840:HSP70 Heat-Shock Proteins; D016222:Fibroblast Growth Factor 2