Self-Assembling Peptide/Thermoresponsive Polymer Composite Hydrogels: Effect of Peptide–Polymer Interactions on Hydrogel Properties

Abstract

We have investigated the effect of doping the self-assembling octapeptide FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine) hydrogels with various amounts of thermoresponsive conjugate of FEFEFKFK and poly(N-isopropylacrylamide) (PNIPAAm) in order to create novel hydrogels. The samples were characterized using a range of techniques including microdifferential scanning calorimetry (μDSC), oscillatory rheology, transmission electron microscopy (TEM), atomic force microscopy (AFM), and small angle neutron scattering (SANS). The peptide from the conjugate was shown to be incorporated into the peptide fiber, resulting in the polymer being anchored to the peptide fiber. The conjugation of the polymer to the peptide and its anchoring to the peptide fibers did not affect its lower critical solution temperature (LCST). On the other hand, it did result in a decrease in the LCST enthalpy and a significant increase in the G' of the hydrogels, suggesting the presence of hydrogen bond interactions between the peptide and the polymer. As a result, the polymer was found to adopt a fibrillar arrangement tightly covering the peptide fiber. The polymer was still found to go through a conformational change at the LCST, suggesting that it collapses onto the peptide fiber. On the other hand, the fibrillar network was found to be mainly unaffected by the polymer LCST. These changes at the LCST were also found to be fully reversible. The nature of the interaction between the polymer and the peptide was shown to have a significant effect on the conformation adopted by the polymer around the fibers and the mechanical properties of the hydrogels.

Supramolecular Peptide/Polymer Hybrid Hydrogels for Biomedical Applications

“…The peptide did not affect the macroscopic phase behavior of the polymer alone. The incorporation of the free peptide in the peptide‐PNIPAAm conjugate disrupted the formation of larger aggregates of collapsed polymer chains, as seen by decreased opacity . This correlates to the role of peptide from the conjugate in interacting with peptide chains that reduce the formation of PNIPAAm globules above LCST point .…”

“…By controlling the ratio of two components, the mechanical behavior and thermo‐responsiveness of the hydrogels were regulated ( Figure 5 A,B) . Peptide conjugation to the polymer did not affect the self‐assembly of the peptide into elongated fibers and had a minimal effect on gelation concentration (≈2 wt%) compared to the peptide hydrogel (Table ) . Increasing the peptide concentration in the hydrogel mixture improved the storage modulus of the hydrogels.…”

“…1.5 (PA) with 4, 8, and 12 of PEGDMA 0.2, 3.5, and 8 [38] Provides porosity in PEG hydrogels NH 2 -FEFEFKFK-OH 1-7 0.006-0.08 [39] PNIPAAm-FEFEFKFK-OH (peptide-polymer conjugation)…”

Injectable hyaluronic acid/PEG-p(HPMAm-lac)-based hydrogels dually cross-linked by thermal gelling and Michael addition

“…This high water content make them compatible with most living tissues.Their viscoelastic and rubbery nature permit their administration into a living host with minimal damage to surrounding tissues, and, ultimately, their mechanical properties can be tailored to closely match those of natural tissues [2,3]. Because of their appealing characteristics, hydrogels, alone or combined with cells, have been used to engineer a variety of tissues in vitro and in vivo [4,5] and, loaded with drugs, found application in the controlled drug delivery field [6,7].…”

Controlling self-assembly of diphenylalanine peptides at high pH using heterocyclic capping groups

“…Whereas microscopy techniques such as transmission electron microscopy (TEM) and atomic force microscopy (AFM) are liable to suffer from the presence of sample preparation artefacts, small angle scattering is conducted on the native hydrogel, providing an accurate statistical three dimensional perspective of the actual hydrogel structure. SANS measurements have been extensively used to probe the native structure of peptide-based hydrogels, most often on hydrogel samples which already exhibit a well-defined network151617181920212223242526. Less well studied is small angle scattering on transitions within gelators; however there are examples of SANS being used to examine the transition of a hexapeptide from ribbons to fibers27 and using SANS to look at the evolution of a pyromellitamide organogel over several days28.…”