title: Toughening of Thermoresponsive Arrested Networks of Elastin-Like Polypeptides To Engineer Cytocompatible Tissue Scaffolds.
abstract: Formulation of tissue engineering or regenerative scaffolds from simple bioactive polymers with tunable structure and mechanics is crucial for the regeneration of complex tissues, and hydrogels from recombinant proteins, such as elastin-like polypeptides (ELPs), are promising platforms to support these applications. The arrested phase separation of ELPs has been shown to yield remarkably stiff, biocontinuous, nanostructured networks, but these gels are limited in applications by their relatively brittle nature. Here, a gel-forming ELP is chain-extended by telechelic oxidative coupling, forming extensible, tough hydrogels. Small angle scattering indicates that the chain-extended polypeptides form a fractal network of nanoscale aggregates over a broad concentration range, accessing moduli ranging from 5 kPa to over 1 MPa over a concentration range of 5-30 wt %. These networks exhibited excellent erosion resistance and allowed for the diffusion and release of encapsulated particles consistent with a bicontinuous, porous structure with a broad distribution of pore sizes. Biofunctionalized, toughened networks were found to maintain the viability of human mesenchymal stem cells (hMSCs) in 2D, demonstrating signs of osteogenesis even in cell media without osteogenic molecules. Furthermore, chondrocytes could be readily mixed into these gels via thermoresponsive assembly and remained viable in extended culture. These studies demonstrate the ability to engineer ELP-based arrested physical networks on the molecular level to form reinforced, cytocompatible hydrogel matrices, supporting the promise of these new materials as candidates for the engineering and regeneration of stiff tissues.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Glassman
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.|Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Cambridge, Massachusetts 02139, United States.|Wyss Institute for Biologically Inspired Engineering, Harvard University , Boston, Massachusetts 02115, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Reginald K
authors.initials: RK
authors.lastname: Avery
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Cambridge, Massachusetts 02139, United States.|Wyss Institute for Biologically Inspired Engineering, Harvard University , Boston, Massachusetts 02115, United States.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Olsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology; D004548:Elasticity; D004549:Elastin / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000502:physiology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D058105:Polymerization; D053838:Scattering, Small Angle; D033081:Shear Strength; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D010455:Peptides; D004549:Elastin