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Tuning the Properties of Elastin Mimetic Hybrid Copolymers via a Modular Polymerization Method

Author:
Grieshaber, Sarah E., Farran, Alexandra J. E., Bai, Shi, Kiick, Kristi L., Jia, Xinqiao
Source:
Biomacromolecules 2012 v.13 no.6 pp. 1774-1786
ISSN:
1526-4602
Subject:
actin, cell growth, composite polymers, crosslinking, elastin, fibroblasts, humans, hydrogels, integrins, peptides, polyethylene glycol, polymerization, tissue engineering
Abstract:
We have synthesized elastin mimetic hybrid polymers (EMHPs) via the step-growth polymerization of azide-functionalized poly(ethylene glycol) (PEG) and alkyne-terminated peptide (AKAAAKA)₂ (AK2) that is abundant in the cross-linking domains of the natural elastin.(1) The modular nature of our synthesis allows facile adjustment of the peptide sequence to modulate the structural and biological properties of EMHPs. Therefore, EMHPs containing cell-binding domains (CBDs) were constructed from α,ω-azido-PEG and two types of alkyne-terminated AK2 peptides with sequences of DGRGX(AKAAAKA)₂X (AK2-CBD1) and X(AKAAAKA)₂XGGRGDSPG (AK2-CBD2, X = propargylglycine) via a step-growth, click coupling reaction. The resultant hybrid copolymers contain an estimated five to seven repeats of PEG and AK2 peptides. The secondary structure of EMHPs is sensitive to the specific sequence of the peptidic building blocks, with CBD-containing EMHPs exhibiting a significant enhancement in the α-helical content as compared with the peptide alone. Elastomeric hydrogels formed by covalent cross-linking of the EMHPs had a compressive modulus of 1.06 ± 0.1 MPa. Neonatal human dermal fibroblasts (NHDFs) were able to adhere to the hydrogels within 1 h and to spread and develop F-actin filaments 24 h postseeding. NHDF proliferation was only observed on hydrogels containing RGDSP domains, demonstrating the importance of integrin engagement for cell growth and the potential use of these EMHPs as tissue engineering scaffolds. These cell-instructive, hybrid polymers are promising candidates as elastomeric scaffolds for tissue engineering.
Agid:
5327272