title: New self-assembling multifunctional templates for the biofabrication and controlled self-release of cultured tissue.
abstract: The need to source live human tissues for research and clinical applications has been a major driving force for the development of new biomaterials. Ideally, these should elicit the formation of scaffold-free tissues with native-like structure and composition. In this study, we describe a biologically interactive coating that combines the fabrication and subsequent self-release of live purposeful tissues using template-cell-environment feedback. This smart coating was formed from a self-assembling peptide amphiphile comprising a protease-cleavable sequence contiguous with a cell attachment and signaling motif. This multifunctional material was subsequently used not only to instruct human corneal or skin fibroblasts to adhere and deposit discreet multiple layers of native extracellular matrix but also to govern their own self-directed release from the template solely through the action of endogenous metalloproteases. Tissues recovered through this physiologically relevant process were carrier-free and structurally and phenotypically equivalent to their natural counterparts. This technology contributes to a new paradigm in regenerative medicine, whereby materials are able to actively direct and respond to cell behavior. The novel application of such materials as a coating capable of directing the formation and detachment of complex tissues solely under physiological conditions can have broad use for fundamental research and in future cell and tissue therapies.
authors.affiliation: 1Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Gouveia
authors.affiliation: 2School of Chemistry, Food and Pharmacy, University of Reading, Reading, United Kingdom.
authors.forename: Valeria
authors.initials: V
authors.lastname: Castelletto
authors.affiliation: 2School of Chemistry, Food and Pharmacy, University of Reading, Reading, United Kingdom.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Hamley
authors.affiliation: 1Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Che J
authors.initials: CJ
authors.lastname: Connon
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion; D020099:Coated Materials, Biocompatible; D003315:Cornea / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D012867:Skin / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology; D013379:Substrate Specificity; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D010455:Peptides; D020783:Matrix Metalloproteinase 7; D020781:Matrix Metalloproteinase 1