Incorporation of PEG Diacrylates (PEGDA) Generates Hybrid Fmoc-FF Hydrogel Matrices

Abstract

Generated by a hierarchical and multiscale self-assembling phenomenon, peptide-based hydrogels (HGs) are soft materials useful for a variety of applications. Short and ultra-short peptides are intriguing building blocks for hydrogel fabrication. These matrices can also be obtained by mixing low-molecular-weight peptides with other chemical entities (e.g., polymers, other peptides). The combination of two or more constituents opens the door to the development of hybrid systems with tunable mechanical properties and unexpected biofunctionalities or morphologies. For this scope, the formulation, the multiscale analysis, and the supramolecular characterization of novel hybrid peptide-polymer hydrogels are herein described. The proposed matrices contain the Fmoc-FF (Nα-fluorenylmethyloxycarbonyl diphenylalanine) hydrogelator at a concentration of 0.5 wt% (5.0 mg/mL) and a diacrylate α-/ω-substituted polyethylene-glycol derivative (PEGDA). Two PEGDA derivatives, PEGDA 1 and PEGDA2 (mean molecular weights of 575 and 250 Da, respectively), are mixed with Fmoc-FF at different ratios (Fmoc-FF/PEGDA at 1/1, 1/2, 1/5, 1/10 mol/mol). All the multicomponent hybrid peptide-polymer hydrogels are scrutinized with a large panel of analytical techniques (including proton relaxometry, FTIR, WAXS, rheometry, and scanning electronic microscopy). The matrices were found to be able to generate mechanical responses in the 2–8 kPa range, producing a panel of tunable materials with the same chemical composition. The release of a model drug (Naphthol Yellow S) is reported too. The tunable features, the different topologies, and the versatility of the proposed materials open the door to the development of tools for different applicative areas, including diagnostics, liquid biopsies and responsive materials. The incorporation of a diacrylate function also suggests the possible development of interpenetrating networks upon cross-linking reactions. All the collected data allow a mutual comparison between the different matrices, thus confirming the significance of the hybrid peptide/polymer-based methodology as a strategy for the design of innovative materials.

Cross-Link of Telechelic Diacrylate Polyethylene-Glycol in Peptide-Based Fmoc-FF Hydrogel Matrices

“…The high-water solubility of both PEGDAs was previously exploited for producing multicomponent Fmoc-FF/PEGDA HGs at four molar ratios (1/1, 1/2, 1/5, and 1/10 mol/mol). 28 This approach allows gel formation in mild conditions, avoiding high temperatures and using a lower amount of PEGDA generally required for other extracellular mimicking peptide matrices. 37,38 should avoid crystalline phase formation, thus promoting a homogeneous PEGDA incorporation in HGs.…”

“…The aqueous phase contains both the PEGDA monomers (in different molar ratios, vide infra ) and the α-HP photoinitiator (Irgacure 2959, 4.46 mmol/L), allowing the one-step inclusion of both hydrophilic components. The high-water solubility of both PEGDAs was previously exploited for producing multicomponent Fmoc-FF/PEGDA HGs at four molar ratios (1/1, 1/2, 1/5, and 1/10 mol/mol) . This approach allows gel formation in mild conditions, avoiding high temperatures and using a lower amount of PEGDA generally required for other extracellular mimicking peptide matrices. , It is worth mentioning that the selected PEGDA molecular weights (MW < 1000 Da) should avoid crystalline phase formation, thus promoting a homogeneous PEGDA incorporation in HGs .…”

“…HGs were prepared using the DMSO/H 2 O “ solvent-switch ” strategy as previously reported . Multicomponent matrices (volume of 400 μL, 0.5 wt % Fmoc-FF concentration) were obtained by hydrating 20 μL of the Fmoc-FF stock (100 mg/mL) with 380 μL of PEGDA/α-HP solutions.…”

“…Simultaneously, the research also moved toward the development of multicomponent systems in which the Fmoc-FF peptide is mixed with other peptide sequences, organic molecules, sugars, and proteins . In this context, we previously described the behavior of Fmoc-FF HGs incorporating diacrylate α-/ω-substituted polyethylene-glycol polymers (PEGDAs, Figure A) . Specifically, these matrices contain alternatively two PEGDAs, namely, PEGDA1 and PEGDA2 (mean molecular weight of 575 and 250 Da, respectively) and are prepared at different peptide/polymer molar ratios (1/1, 1/2, 1/5, and 1/10 mol/mol).…”

Bioactive Polyurethane–Poly(ethylene Glycol) Diacrylate Hydrogels for Applications in Tissue Engineering

“…One challenge in hydrogel development is the need to improve mechanical strength and limited biocompatibility [8]; therefore, there has been a great effort to improve the mechanical properties and bio-functionality of hydrogels through the development of hybrid natural/synthetic hydrogel materials [9][10][11]. Such design efforts to improve biocompatibility and flexibility/toughness with tunable chemistry promote the application of hydrogels in multiple research areas, such as wound dressing, drug delivery, tissue engineering, and smart sensing (e.g., temperature, pH, enzymes) [12][13][14][15][16][17][18].…”