Synthesis and Characterization of Elastin−Mimetic Hybrid Polymers with Multiblock, Alternating Molecular Architecture and Elastomeric Properties

Abstract

We are interested in developing elastin–mimetic hybrid polymers (EMHPs) that capture the multiblock molecular architecture of tropoelastin as well as the remarkable elasticity of mature elastin. In this study, multiblock EMHPs containing flexible synthetic segments based on poly(ethylene glycol) (PEG) alternating with alanine-rich, lysine-containing peptides were synthesized by step-growth polymerization using α,ω-azido-PEG and alkyne-terminated AKA3KA (K = lysine, A = alanine) peptide, employing orthogonal click chemistry. The resulting EMHPs contain an estimated three to five repeats of PEG and AKA3KA and have an average molecular weight of 34 kDa. While the peptide alone exhibited α-helical structures at high pH, the fractional helicity for EMHPs was reduced. Covalent cross-linking of EMHPs with hexamethylene diisocyanate (HMDI) through the lysine residue in the peptide domain afforded an elastomeric hydrogel (xEMHP) with a compressive modulus of 0.12 MPa when hydrated. The mechanical properties of xEMHP are comparable to a commercial polyurethane elastomer (Tecoflex SG80A) under the same conditions. In vitro toxicity studies showed that while the soluble EMHPs inhibited the growth of primary porcine vocal fold fibroblasts (PVFFs) at concentrations ≥0.2 mg/mL, the cross-linked hybrid elastomers did not leach out any toxic reagents and allowed PVFFs to grow and proliferate normally. The hybrid and modular approach provides a new strategy for developing elastomeric scaffolds for tissue engineering.

Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration

“…[150] The multiblock elastin-mimetic hybrid polymers (EMHPs) are composed of alternating poly (ethylene glycol) block and alanine-rich, lysine-containing elastin-peptide block synthesized via azido-alkyne mediated orthogonal click reaction. [151,152] EMHPs can be chemically crosslinked with hexamethylene diisocyanate (HMDI) to form elastomeric hydrogels with compressive modulus close to 0.12MPa when hydrated and without exhibiting any deleterious effects to the growth of primary porcine vocal fold fibroblasts (PVFFs).…”

Biomaterial-based strategies for the engineering of mechanically active soft tissues

“…The resultant multiblock copolymers (Figure 1), when covalently crosslinked, exhibit mechanical properties similar to natural elastin and are capable of supporting the attachment and proliferation of fibroblasts. 24-26 Intrigued by the superior resilience and excellent high-frequency responsiveness of resilin found in specialized compartments of most arthropods, researchers have produced recombinant resilin-like polypeptide bearing both mechanically active 27, 28 and biologically active domains. These materials are being used for vocal fold tissue engineering.…”

Synthesis and bioactivity of MSH4 oligomers prepared by an A2+ B2 strategy

“…33–36 Finally, an A 2 + B 2 assembly strategy was selected over an AB strategy in order that the oligomer structure might be more easily altered (by changing out the B 2 co-monomer) and to limit macrocyclization. 34,37 …”