Self-assembled nanofibers and hydrogels of double-hydrophobic elastin-like polypeptides formed via coacervation

Peptide hydrogels are highly hydrophilic, three-dimensional network gels formed by the self-assembly of nanofibers or polymers, creating water-locking networks. Their morphology closely resembles that of the extracellular matrix, allowing them to exhibit both the biological functions of peptides and responsive gelation properties. These unique characteristics have led to their extensive application in tissue engineering, three-dimensional cell culture, cancer therapy, regenerative medicine, and other biomedical fields. This article describes three methods for preparing ECF-5 peptide hydrogels using self-assembling peptides with environmentally responsive gelation processes: (1) pH-responsive gelation: varying pH levels induce the protonation or deprotonation of amino acid residues, altering electrostatic interactions between peptide molecules and promoting their self-assembly into hydrogels; (2) Metal ion addition: polyvalent metal ions chelate with negatively charged amino acid residues, acting as bridges between peptides to form a network hydrogel; (3) Solvent exchange: hydrophobic peptides are initially dissolved in non-polar organic solvents and subsequently induce self-assembly into hydrogels upon transitioning to a polar aqueous environment. These methods utilize conventional experimental procedures to facilitate peptide self-assembly into hydrogels. By designing peptide sequences to align with specific gelation-inducing conditions, it is possible to achieve finely tuned micro/nanostructures and biological functions, highlighting the significant potential of peptide hydrogels in the biomedical domain.

Strategic materials design is essential for the development of small-diameter, tissue-engineered vascular grafts. Self-assembled nanofibers of elastin-like polypeptides represent promising vascular graft components as they replicate the organized elastin structure of native blood vessels. Further, the bioactivity of nanofibers can be modified by the addition of functional peptide motifs. In the present study, we describe the development of a novel nanofiber-forming elastin-like polypeptide (ELP) with an arginine–glutamic acid–aspartic acid–valine (REDV) sequence. The biological characteristics of the REDV-modified ELP nanofibers relevant to applications in vascular grafting were compared to ELP without ligands for integrin, ELP with arginine–glycine–aspartic acid (RGD) sequence, collagen and cell culture glass. Among them, REDV-modified ELP nanofibers met the preferred biological properties for vascular graft materials, i.e. (i) inhibition of platelet adhesion and activation, (ii) endothelial cell adhesion and proliferation and (iii) maintenance of smooth muscle cells in a contractile phenotype to prevent cell overgrowth. The results indicate that REDV-modified ELP nanofibers represent promising candidates for the further development of small-diameter vascular grafts.

Atopic Dermatitis (AD) is a chronic inflammatory skin disease that is prone to recurrent episodes, posing numerous challenges in treatment, especially due to the systemic side effects often caused by existing medications. Effectively controlling microbial infections and modulating oxidative stress levels are key strategies in the treatment of AD. In the present study, we developed an injectable antimicrobial hydrogel (J-1-VcNa hydrogel), formed by the self-assembled nanofibers of the natural antimicrobial peptide Jelleine-1 in a phosphate buffer solution of the natural antioxidant sodium ascorbate (VcNa), without the addition of any cross-linking agents. The formation of J-1-VcNa hydrogel was primarily driven by hydrogen bonds and hydrophobic interactions. Our results indicated that it not only exhibited broad-spectrum antimicrobial properties but also possessed efficient reactive oxygen species (ROS) scavenging capabilities. Notably, in a mouse model of AD, J-1-VcNa hydrogel demonstrated significant therapeutic potential, effectively reducing pathogen colonization and significantly improving AD skin lesions by modulating the oxidative stress-inflammatory cascade. Additionally, the hydrogel exhibited good biocompatibility and biodegradability. These findings suggested that J-1-VcNa hydrogel held potential for clinical use in the treatment of AD. Therefore, this study would offer a promising therapeutic strategy for the treatment of AD.

Vitamin C supramolecular hydrogel for enhanced cancer immunotherapy