Abstract/Details

Recombinant elastin -mimetic protein polymers as design elements for an arterial substitute


2008 2008

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Abstract (summary)

Genetic engineering has been employed in the design of novel protein polymers composed of repetitive amino acid sequences or peptide blocks whose structural complexity imparts distinct mechanical, chemical or biological properties. Recently, we have reported the synthesis of elastin-mimetic multiblock copolymer composed of identical endblocks derived from self-associating, hydrophobic sequences that display plastic-like mechanical responses (Ile-Pro-Ala-Val-Gly), separated by a central block that is both hydrophilic and elastomeric (Val-Pro-Gly-Glu-Gly). Significantly, these multiblock systems afford the ability to form physical or virtual crosslinked networks through the self-association of chemically similar domains under physiologically relevant conditions (pH 7.4, 37°C).

Recombinant synthesis of elastin-mimetic proteins has been employed for several decades, however, long-term biocompatibility and biostability of such proteins was not fully defined. We present virtually crosslinked elastin-mimetic proteins which exhibit exceptional biocompatibility and long-term biostability over a period of at least seven months. This report is the first evidence of a non-chemically or ionically crosslinked system that exhibits long-term in vivo stability.

Although, physically crosslinked protein-based materials possess a number of advantages over their chemically crosslinked counterparts, physical crosslinks and the related domains so formed may be deformed or damaged at applied stresses lower than those required to disrupt covalent crosslinks. In this regard, we have synthesized a new class of recombinant elastin-mimetic triblock copolymer capable of both physical and chemical crosslinking. We have demonstrated that chemical crosslinking provides an independent mechanism for control of protein mechanical responses. Specifically, elastic modulus was enhanced and creep strain reduced through the addition of chemical crosslinking sites.

A number of reports have described the design of synthetic genes, which encode elastin-like proteins for bacterial expression in Escherichia coli. Although advantages with this expression system exist, significant limitations including the lack of eukaryotic post-translational systems, the tendency to sequester mammalian proteins into inclusion bodies, difficult purification protocols, and endotoxin contamination have been noted. We demonstrate the expression of a recombinant elastin-mimetic protein from P. pastoris . A novel synthetic strategy, monomer library concatamerization, was utilized in designing non-repetitive elastin genes for highly repetitive protein sequences. It is likely that this strategy will be useful for creating large, repetitive genes for a variety of expression systems in order to more closely approach the genetic diversity inherent to native DNA sequences.

All told, elastin-based protein polymers are a promising class of material characterized by high degree of biocompatibility, excellent biostability, and a tunable range of mechanical properties from plastic to elastic. A variety of options facilitate the processing of these biopolymers into chemically crosslinked or non-crosslinked gels, films, or nanofibers for any of a number of implant applications including structural components of artificial organs and engineered living tissues, carriers for controlled drug release, or biocompatible surface coatings.

Indexing (details)


Subject
Biomedical engineering
Classification
0541: Biomedical engineering
Identifier / keyword
Applied sciences; Elastin-mimetic; Genetic engineering; Protein expression; Protein polymers; Recombinant
Title
Recombinant elastin -mimetic protein polymers as design elements for an arterial substitute
Author
Sallach, Rory Elizabeth
Number of pages
192
Publication year
2008
Degree date
2008
School code
0078
Source
DAI-B 70/11, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781109452525
Advisor
Chaikof, Elliot L.
University/institution
Georgia Institute of Technology
University location
United States -- Georgia
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3376347
ProQuest document ID
304656947
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304656947
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