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. 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 demonstratemore »
- Authors:
-
- Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
- 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)
- 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)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- US Army Research Office (ARO)
- OSTI Identifier:
- 1240186
- Grant/Contract Number:
- W911NF-07-D-0004
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Biomacromolecules
- Additional Journal Information:
- Journal Volume: 17; Journal Issue: 2; Journal ID: ISSN 1525-7797
- Publisher:
- American Chemical Society
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Anatomy; Peptides and proteins; Biomaterials; Scattering; Gels
Citation Formats
Glassman, Matthew J., Avery, Reginald K., Khademhosseini, Ali, and Olsen, Bradley D. Toughening of Thermoresponsive Arrested Networks of Elastin-Like Polypeptides To Engineer Cytocompatible Tissue Scaffolds. United States: N. p., 2016.
Web. doi:10.1021/acs.biomac.5b01210.
Glassman, Matthew J., Avery, Reginald K., Khademhosseini, Ali, & Olsen, Bradley D. Toughening of Thermoresponsive Arrested Networks of Elastin-Like Polypeptides To Engineer Cytocompatible Tissue Scaffolds. United States. https://doi.org/10.1021/acs.biomac.5b01210
Glassman, Matthew J., Avery, Reginald K., Khademhosseini, Ali, and Olsen, Bradley D. Wed .
"Toughening of Thermoresponsive Arrested Networks of Elastin-Like Polypeptides To Engineer Cytocompatible Tissue Scaffolds". United States. https://doi.org/10.1021/acs.biomac.5b01210. https://www.osti.gov/servlets/purl/1240186.
@article{osti_1240186,
title = {Toughening of Thermoresponsive Arrested Networks of Elastin-Like Polypeptides To Engineer Cytocompatible Tissue Scaffolds},
author = {Glassman, Matthew J. and Avery, Reginald K. and Khademhosseini, Ali and Olsen, Bradley D.},
abstractNote = {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.},
doi = {10.1021/acs.biomac.5b01210},
journal = {Biomacromolecules},
number = 2,
volume = 17,
place = {United States},
year = {Wed Jan 20 00:00:00 EST 2016},
month = {Wed Jan 20 00:00:00 EST 2016}
}
Web of Science
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