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Title: Toughening of Thermoresponsive Arrested Networks of Elastin-Like Polypeptides To Engineer Cytocompatible Tissue Scaffolds

Journal Article · · Biomacromolecules
 [1];  [2];  [3];  [1]
  1. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
  2. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Harvard Medical School, Boston, MA (United States). Brigham and Women's Hospital; Harvard Univ., Cambridge, MA (United States)
  3. Harvard Medical School, Boston, MA (United States). Brigham and Women's Hospital; Harvard Univ., Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

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. Furthermore, 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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
US Army Research Office (ARO)
Grant/Contract Number:
W911NF-07-D-0004
OSTI ID:
1240186
Journal Information:
Biomacromolecules, Vol. 17, Issue 2; ISSN 1525-7797
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 39 works
Citation information provided by
Web of Science

References (52)

Complexity in biomaterials for tissue engineering journal June 2009
Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology journal June 2006
Injectable hydrogel materials for spinal cord regeneration: a review journal January 2012
Injectable matrices and scaffolds for drug delivery in tissue engineering journal May 2007
In situ gelling hydrogels for pharmaceutical and biomedical applications journal May 2008
Hydrogels for tissue engineering: scaffold design variables and applications journal November 2003
Two-component protein-engineered physical hydrogels for cell encapsulation journal December 2009
Yielding Behavior in Injectable Hydrogels from Telechelic Proteins journal November 2010
Thermoreversible hydrogel scaffolds for articular cartilage engineering journal January 2004
Astrocyte infiltration into injectable collagen-based hydrogels containing FGF-2 to treat spinal cord injury journal May 2013
Injectable Biomaterials for Regenerating Complex Craniofacial Tissues journal September 2009
Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering journal November 2002
Shape Retaining Injectable Hydrogels for Minimally Invasive Bulking journal August 2004
Responsive reversible hydrogels from associative “smart” macromolecules journal January 2010
Arrested Phase Separation of Elastin-like Polypeptide Solutions Yields Stiff, Thermoresponsive Gels journal November 2015
Protein-Based Materials with a Profound Range of Properties and Applications: The Elastin ΔTt Hydrophobic Paradigm book January 1997
Elastin-like polypeptides: Biomedical applications of tunable biopolymers journal January 2010
Recombinant elastin-mimetic biomaterials: Emerging applications in medicine journal December 2010
Self-assembly of block copolymers derived from elastin-mimetic polypeptide sequences journal October 2002
Physical Chemistry of Biological Free Energy Transduction As Demonstrated by Elastic Protein-Based Polymers journal December 1997
A Unified Model for De Novo Design of Elastin-like Polypeptides with Tunable Inverse Transition Temperatures journal July 2013
Double-Network Hydrogels with Extremely High Mechanical Strength journal July 2003
Progress in the development of interpenetrating polymer network hydrogels journal January 2008
Preparation and characterization of pH-sensitive, interpenetrating networks of poly(vinyl alcohol) and poly(acrylic acid) journal February 1995
Highly Extensible, Tough, and Elastomeric Nanocomposite Hydrogels from Poly(ethylene glycol) and Hydroxyapatite Nanoparticles journal May 2011
Nanocomposite hydrogels for biomedical applications: Nanocomposite Hydrogels journal December 2013
Oxidatively Responsive Chain Extension to Entangle Engineered Protein Hydrogels journal January 2014
Why are double network hydrogels so tough? journal January 2010
Lamellar Bilayers as Reversible Sacrificial Bonds To Toughen Hydrogel: Hysteresis, Self-Recovery, Fatigue Resistance, and Crack Blunting journal November 2011
Physical hydrogels composed of polyampholytes demonstrate high toughness and viscoelasticity journal July 2013
Structure and Mechanism of Strength Enhancement in Interpenetrating Polymer Network Hydrogels journal July 2011
Oxidation increases mucin polymer cross-links to stiffen airway mucus gels journal February 2015
Protein–protein crosslinking in food: methods, consequences, applications journal December 2002
New measures for characterizing nonlinear viscoelasticity in large amplitude oscillatory shear journal November 2008
A geometrical interpretation of large amplitude oscillatory shear response journal May 2005
Reduction and analysis of SANS and USANS data using IGOR Pro journal November 2006
Simulation of bicontinuous microemulsions: comparison of simulated real-space microstructures with scattering experiments journal October 1991
Mesoscopic scale structures in self-organized surfactant solutions determined by small-angle neutron scattering journal July 1998
Structural evolution of bicontinuous microemulsions journal September 1991
Morphological Characterization of Bicontinuous Phase-Separated Polymer Blends and One-Phase Microemulsions journal January 1997
SAXS Measurements of Interfacial Thickness in Amorphous Polymer Blends Containing a Diblock Copolymer journal March 1994
Investigation of non-ideal two-phase polymer structures by small-angle X-ray scattering journal April 1973
Measurement of the Gaussian curvature of the surfactant film in an isometric bicontinuous one-phase microemulsion journal December 1996
A review of nonlinear oscillatory shear tests: Analysis and application of large amplitude oscillatory shear (LAOS) journal December 2011
Large amplitude oscillatory shear of pseudoplastic and elastoviscoplastic materials journal December 2009
Matrix Elasticity Directs Stem Cell Lineage Specification journal August 2006
Osteoblast adhesion on biomaterials journal April 2000
Biomaterials and bone mechanotransduction journal October 2001
Osteocalcin Secretion as an Early Marker of In Vitro Osteogenic Differentiation of Rat Mesenchymal Stem Cells journal June 2009
The role of alkaline phosphatase in mineralization journal January 2007
Osteopontin journal July 2000
Three-Dimensional Microenvironments Retain Chondrocyte Phenotypes During Proliferation Culture journal July 2007

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Glycosaminoglycan-based resorbable polymer composites in tissue refurbishment journal April 2017
Designing Smart Materials with Recombinant Proteins journal March 2017
Supramolecular and dynamic covalent hydrogel scaffolds: from gelation chemistry to enhanced cell retention and cartilage regeneration journal January 2019
Elastin-like polypeptides as building motifs toward designing functional nanobiomaterials journal January 2019
Double-hydrophobic elastin-like polypeptides with added functional motifs: Self-assembly and cytocompatibility journal June 2017
Injectable tissue integrating networks from recombinant polypeptides with tunable order journal October 2018