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. 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 » 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.« less

Authors:

Glassman, Matthew J. ^[1]; Avery, Reginald K. ^[2]; Khademhosseini, Ali ^[3]; Olsen, Bradley D. ^[1]

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+ Show Author Affiliations

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)

Publication Date:

Wed Jan 20 00:00:00 EST 2016

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:

Journal Article: 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