Localized Enzyme-Assisted Self-Assembly in the Presence of Hyaluronic Acid for Hybrid Supramolecular Hydrogel Coating

Abstract

Hydrogel coating is highly suitable in biomaterial design. It provides biocompatibility and avoids protein adsorption leading to inflammation and rejection of implants. Moreover, hydrogels can be loaded with biologically active compounds. In this field, hyaluronic acid has been largely studied as an additional component since this polysaccharide is naturally present in extracellular matrix. Strategies to direct hydrogelation processes exclusively from the surface using a fully biocompatible approach are rare. Herein we have applied the concept of localized enzyme-assisted self-assembly to direct supramolecular hydrogels in the presence of HA. Based on electronic and fluorescent confocal microscopy, rheological measurements and cell culture investigations, this work highlights the following aspects: (i) the possibility to control the thickness of peptide-based hydrogels at the micrometer scale (18–41 µm) through the proportion of HA (2, 5 or 10 mg/mL); (ii) the structure of the self-assembled peptide nanofibrous network is affected by the growing amount of HA which induces the collapse of nanofibers leading to large assembled microstructures underpinning the supramolecular hydrogel matrix; (iii) this changing internal architecture induces a decrease of the elastic modulus from 2 to 0.2 kPa when concentration of HA is increasing; (iv) concomitantly, the presence of HA in supramolecular hydrogel coatings is suitable for cell viability and adhesion of NIH 3T3 fibroblasts.

Mechanistic Insights into Hyaluronic Acid Induced Peptide Nanofiber Organization in Supramolecular Hydrogels

“…In previous studies, CLSM has proven to be useful in studying the nanofibrous network of peptide self-assemblies . We used HA labeled by rhodamine (HA RHO ) and the Fmoc-FFY self-assembly was visualized by the presence of thioflavine T (ThT, λ ex = 350 nm; λ em = 438 nm) which fluoresces in the green region of the visible spectrum when interacting with hydrophobic β-sheet structures.…”

“…A correlation image analysis between the red and the green colors removes any doubts about the full colocalization of HA and Fmoc-FFY self-assembly (Figure S5). It is important to note that when HA is not labeled (Figure b), similar bundles are observed by confocal microscopy . In addition, using HA RHO in absence of ThT results in the observation of typical red-colored bundles (Figure S6).…”

“…HA (PrimaHyal from Givaudan) M w 406000 g·mol –1 , polydispersity 1.574) is sold by Givaudan. Its full 1 H NMR and size exclusion chromatography characterization have been given previsously . Rhodaminated HA was prepared from HA following a reported procedure .…”

Immunomodulatory fibrous hyaluronic acid‐Fmoc‐diphenylalanine‐based hydrogel induces bone regeneration

“…Incorporating FmocFF, a short aromatic self‐assembling peptide, into a HA matrix produces a biomimetic structure in which FmocFF resembles the collagen fibrils and the HA resembles the glycosaminoglycans, which are the two main components of native ECM (Aviv et al, 2018 ). A similar interaction between HA and a tripeptide hydrogelator, Fmoc‐FFΥ, by localized enzyme‐assisted self‐assembly approach has formed hydrogel coatings in various thicknesses determined by the concentration of the HA (Rodon Fores et al, 2021 ).…”

Surface-controlled spatially heterogeneous physical properties of a supramolecular gel with homogeneous chemical composition

“…Recently, the addition of hyaluronic acid to an enzyme triggered peptide-based gelator was shown to result in different mechanical properties of the hydrogel. 15 …”