Development of Polyurethane/Peptide-Based Carriers with Self-Healing Properties

Abstract

In situ-forming gels with self-assembling and self-healing properties are materials of high interest for various biomedical applications, especially for drug delivery systems and tissue regeneration. The main goal of this research was the development of an innovative gel carrier based on dynamic inter- and intramolecular interactions between amphiphilic polyurethane and peptide structures. The polyurethane architecture was adapted to achieve the desired amphiphilicity for self-assembly into an aqueous solution and to facilitate an array of connections with peptides through physical interactions, such as hydrophobic interactions, dipole-dipole, electrostatic, π–π stacking, or hydrogen bonds. The mechanism of the gelation process and the macromolecular conformation in water were evaluated with DLS, ATR-FTIR, and rheological measurements at room and body temperatures. The DLS measurements revealed a bimodal distribution of small (~30–40 nm) and large (~300–400 nm) hydrodynamic diameters of micelles/aggregates at 25 °C for all samples. The increase in the peptide content led to a monomodal distribution of the peaks at 37 °C (~25 nm for the sample with the highest content of peptide). The sol–gel transition occurs very quickly for all samples (within 20–30 s), but the equilibrium state of the gel structure is reached after 1 h in absence of peptide and required more time as the content of peptide increases. Moreover, this system presented self-healing properties, as was revealed by rheological measurements. In the presence of peptide, the structure recovery after each cycle of deformation is a time-dependent process, the recovery is complete after about 300 s. Thus, the addition of the peptide enhanced the polymer chain entanglement through intermolecular interactions, leading to the preparation of a well-defined gel carrier. Undoubtedly, this type of polyurethane/peptide-based carrier, displaying a sol–gel transition at a biologically relevant temperature and enhanced viscoelastic properties, is of great interest in the development of medical devices for minimally invasive procedures or precision medicine.

Thermosensitive Polyurethane-Based Hydrogels as Potential Vehicles for Meloxicam Delivery

“…For τ > τ o , J(t) changes its trend and starts to increase due to the preponderance of the viscous flow. Similar behavior was reported for PU/peptide systems [46]. However, an anti-creep behavior was observed for Sample 6 (Figure 8D) due to the EO presence.…”

“…The temperature increase determines the intensification of hydrophobic interactions and the formation of micelles with the hydrophobic core and hydrophilic shell. The gelation of PU is attributed to the formation of a polymicellar network structure [46], when a sharp variation in the viscoelastic parameters takes place. In the gel state, G > G and tan δ < 1.…”

“…The behavior of Samples 4 and 5 is strongly influenced by HPC addition. The highly entangled HPC chains and PU micelles [46,47] form an interpenetrating network with preponderant hydrophilic interactions at low temperatures, ensuring the homogenization of the polymer mixtures in solution. By raising the temperature, the hydrophobic interactions are developed by both polymers and determine an increase in the viscoelastic moduli.…”

Self-Healing of Pluronic® F127 Hydrogels in the Presence of Various Polysaccharides

“…Thus, σ o can be considered as the upper value of shear stress, corresponding to the point that delimitates the linear and non-linear ranges of viscoelasticity. Usually, the value determined by this method overestimates the yield stress [ 54 , 56 , 60 ]. Thus, the σ o values determined from these tests for XG solutions and PL-based hydrogels ( Table 1 ) were higher compared with those determined in the continuous shear tests.…”

Diversity of Bioinspired Hydrogels: From Structure to Applications

“…These materials are inspired by the biological role of polysaccharides, proteins, and peptides in nature. A challenge assumed by researchers is the design of novel peptide/polymer materials with targeted properties [21]. The novel strategies involve either the design of peptide amphiphiles or the replication of protein secondary structural motifs, such as α-helix and β-sheet.…”