Study on cellulose nanofibrils/copolymacrolactone based nano-composites with hydrophobic behaviour, self-healing ability and antioxidant activity.

The multiple uses of cellulose nanofibrils (CNFs) originate from their availability from renewable resources, and are due to their physico-chemical properties, biodegradability and biocompatibility. At the same time, reducing sensitivity to humidity, increasing interfacial adhesion and hydrophobic modification of the CNF surface to diversify applications and improve operation, are current targets pursued. This study focuses on the preparation of a novel gel structure using cellulose nanofibrils (CNFs) and poly(ethylene brassylate-co-squaric acid) (PEBSA50/50), a bio-based copolymacrolactone. The primary goal is to achieve the gel with reduced sensitivity to humidity and enhanced hydrophobic behaviour. The new system was characterized in comparison to its constituent components using various techniques, such as Fourier transform infrared spectroscopy, thermal analysis, X-ray diffraction, and NIR - chemical imaging. Rheological tests demonstrated the formation of the CNF_PEBSA50/50 gel as a result of physical interactions between the two polymeric partners and revealed self-healing abilities for the prepared gels. Determination of the contact angle, surface free energy, as well as dynamic measurements of the vapour sorption of the CNF_PEBSA50/50 system, confirmed the achievement of the study's aim. Furthermore, the CNF_PEBSA50/50 network was utilized to encapsulate citric acid, resulting in the creation of a new bioactive composite with both antioxidant and antimicrobial activity.

Morphological Evaluation of Supramolecular Soft Materials Obtained through Co-Assembly Processes.

Low-molecular-weight gelators (LMWGs) are compounds with an intrinsic tendency to self-assemble forming various supramolecular architectures via non-covalent interactions. Considering that the development of supramolecular assemblies through the synergy of molecules is not entirely understood at the molecular level, this study introduced a Fmoc-short peptide and four Fmoc-amino acids as building blocks for the self-assembly/co-assembly process. Hence, we investigated the formation of supramolecular gels starting from the molecular aggregation following two triggering approaches: solvent/co-solvent method and pH switch. The complex morphological analysis (POM, AFM, and STEM) offered an insight into the spontaneous formation of well-ordered nanoaggregates. Briefly, POM and AFM images demonstrated that self-assembled gels present various morphologies like dendrimer, spherulite, and vesicle, whereas all co-assembled supramolecular systems exhibit fibrillar morphologies as a result of the interaction between co-partners of each system. STEM study has confirmed that the molecules interact and join together, finally forming a fibrous network, an aspect seen in both self-assembled and co-assembled gels. XRD allowed the determination of the molecular arrangement. The study emphasized that the Fmoc motif protected the amino groups and facilitated gelation through additional π-π interactions.

Alginate-Based Hydrogels Enriched with Lavender Essential Oil: Evaluation of Physicochemical Properties, Antimicrobial Activity, and In Vivo Biocompatibility.

Owing to its antibacterial, anti-inflammatory, and antioxidant activities, in the last few years, lavender essential oil (LVO) has been used in medical applications as a promising approach for treating infected wounds. However, the practical applicability of LVO is limited by its high volatility and storage stability. This study aimed to develop a novel hybrid hydrogel by combining phytic acid (PA)-crosslinked sodium alginate (SA) and poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5] undecane (PITAU) and evaluate its potential effectiveness as an antibacterial wound dressing after incorporating LVO. The influence of the mass ratio between SA and PITAU on the properties and stability of hydrogels was investigated. After LVO loading, the effect of oil addition to hydrogels on their functional properties and associated structural changes was studied. FTIR analysis revealed that hydrogen bonding is the primary interaction mechanism between components in the hybrid hydrogels. The morphology was analyzed using SEM, evidencing a porosity dependent on the ratio between SA and PITAU, while LVO droplets were well dispersed in the polymer blend. The release of LVO from the hydrogels was determined using UV-VIS spectroscopy, indicating a sustained release over time, independent of the LVO concentration. In addition, the hybrid hydrogels were tested for their antioxidant properties and antimicrobial activity against Gram-positive and Gram-negative bacteria. Very good antimicrobial activity was obtained in the case of sample SA_PITAU3+LVO10% against S. aureus and C. albicans. Moreover, in vivo tests showed an increased antioxidant effect of the SA_PITAU3+LVO10% hydrogel compared to the oil-free scaffold that may aid in accelerating the healing process of wounds.

Injectable Networks Based on a Hybrid Synthetic/Natural Polymer Gel and Self-Assembling Peptides Functioning as Reinforcing Fillers.

Double network (DN) hydrogels composed of self-assembling low-molecular-weight gelators and a hybrid polymer network are of particular interest for many emerging biomedical applications, such as tissue regeneration and drug delivery. The major benefits of these structures are their distinct mechanical properties as well as their ability to mimic the hierarchical features of the extracellular matrix. Herein, we describe a hybrid synthetic/natural polymer gel that acts as the initial network based on sodium alginate and a copolymer, namely poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5,5) undecane). The addition of amino acids and peptide-derived hydrogelators, such as Fmoc-Lys-Fmoc-OH and Fmoc-Gly-Gly-Gly-OH, to the already-made network gives rise to DNs crosslinked via non-covalent interactions. Fourier transform infrared spectroscopy (FTIR) and thermal analysis confirmed the formation of the DN and highlighted the interactions between the two component networks. Swelling studies revealed that the materials have an excellent water absorption capacity and can be classified as superabsorbent gels. The rheological properties were systematically investigated in response to different variables and showed that the prepared materials present injectability and a self-healing ability. SEM analysis revealed a morphology consisting of a highly porous and interconnected fibrous network. Finally, the biocompatibility was evaluated using the MTT assay on dermal fibroblasts, and the results indicated that the new structures are non-toxic and potentially useful for biomedical applications.

New Hydrogels Based on Agarose/Phytagel and Peptides.

Short aromatic peptide derivatives, i.e., peptides or amino acids modified with aromatic groups, such as 9-fluorenylmethoxycarbonyl (Fmoc), can self-assemble into extracellular matrix-like hydrogels due to their nanofibrillar architecture. Among different types of amino acids, lysine (Lys) and glycine (Gly) are involved in multiple physiological processes, being key factors in the proper growth of cells, carnitine production, and collagen formation. The authors have previously successfully presented the possibility of obtaining supramolecular gels based on Fmoc-Lys-Fmoc and short peptides such as Fmoc-Gly-Gly-Gly in order to use them as a substrate for cell cultures. This paper investigates how the introduction of a gelling polymer can influence the properties of the network as well as the compatibility of the resulting materials with different cell types. A series of hydrogel compositions consisting of combinations of Fmoc-Lys-Fmoc and Fmoc-Gly-Gly-Gly with Agarose and Phytagel are thus obtained. All compositions form structured gels as shown by rheological studies and scanning electron microscopy. Fourier transform infrared spectroscopy analysis evidences the formation of H-bonds between the polysaccharides and amino acids or short peptides. Moreover, all gels exhibit good cell viability on fibroblasts as demonstrated by a live-dead staining test and good in vivo biocompatibility, which highlights the great potential of these biomaterials for biomedical applications.

New Fmoc-Amino Acids/Peptides-Based Supramolecular Gels Obtained through Co-Assembly Process: Preparation and Characterization.

One of the methods of obtaining supramolecular gels consists of the possibility of self-assembly of low molecular weight gelators (LMWGs). However, LMWG-based gels are often difficult to handle, easy to destroy and have poor rheological performance. In order to improve the gels' properties, the LMWGs molecules are co-assembled, which induces more cross-links with more stable structures. Starting from these aspects, the present study refers to the preparation of a bionic hydrogel stabilized with a physiologically occurring, bifunctional biomolecule, L-lysine, co-assembled with other amino acids or peptides (such as a modified amino acid (Fmoc-serine or Fmoc-glutamic acid) or a tripeptide (Fmoc-Gly-Gly-Gly)) with the potential to support the repair of injuries or the age-related impaired structures or functions of living tissues. The introduction of a copartner aims to improve hydrogel characteristics from a morphological, rheological and structural point of view. On the other hand, the process will allow the understanding of the phenomenon of specific self-association and molecular recognition. Various characterization techniques were used to assess the ability to co-assemble: DLS, FT-IR, SEM and fluorescence microscopy, rheology and thermal analysis. Studies have confirmed that the supramolecular structure occurs through the formation of inter- and intramolecular physical bonds that ensure the formation of fibrils organized into 3D networks. The rheological data, namely the G' > G″ and tan δ approximately 0.1−0.2 gel-like behavior observed for all studied samples, demonstrate and sustain the appearance of the co-assembly processes and the ability of the samples to act as LMWG. From the studied systems, the Fmoc−Lys−Fmoc_ Fmoc−Glu sample presented the best rheological characteristics that are consistent with the observations that resulted from the dichroism, fluorescence and SEM investigations.

Drug-Loaded Polymeric Particulated Systems for Ophthalmic Drugs Release.

Drug delivery to the anterior or posterior segments of the eye is a major challenge due to the protection barriers and removal mechanisms associated with the unique anatomical and physiological nature of the ocular system. The paper presents the preparation and characterization of drug-loaded polymeric particulated systems based on pre-emulsion coated with biodegradable polymers. Low molecular weight biopolymers (chitosan, sodium hyaluronate and heparin sodium) were selected due to their ability to attach polymer chains to the surface of the growing system. The particulated systems with dimensions of 190-270 nm and a zeta potential varying from -37 mV to +24 mV depending on the biopolymer charges have been obtained. Current studies show that particles release drugs (dexamethasone/pilocarpine/bevacizumab) in a safe and effective manner, maintaining therapeutic concentration for a longer period of time. An extensive modeling study was performed in order to evaluate the drug release profile from the prepared systems. In a multifractal paradigm of motion, nonlinear behaviors of a drug delivery system are analyzed in the fractal theory of motion, in order to correlate the drug structure with polymer. Then, the functionality of a SL(2R) type "hidden symmetry" implies, through a Riccati type gauge, different "synchronization modes" (period doubling, damped oscillations, quasi-periodicity and intermittency) during the drug release process. Among these, a special mode of Kink type, better reflects the empirical data. The fractal study indicated more complex interactions between the angiogenesis inhibitor Bevacizumab and polymeric structure.

Synthesis and Comparative Studies of Glucose Oxidase Immobilized on Fe3O4 Magnetic Nanoparticles Using Different Coupling Agents.

Squaric acid (SA) is a compound with potential to crosslink biomacromolecules. Although SA has become over the last years a well-known crosslinking agent as a result of its good biocompatibility, glutaraldehyde (GA), a compound with proven cytotoxicity is still one of the most used crosslinkers to develop nanomaterials. In this regard, the novelty of the present study consists in determining whether it may be possible to substitute GA with a new bifunctional and biocompatible compound, such as SA, in the process of enzyme immobilization on the surface of magnetic nanoparticles (MNPs). Thus, a direct comparison between SA- and GA-functionalized magnetic nanoparticles was realized in terms of physico-chemical properties and ability to immobilize catalytic enzymes. The optimal conditions of the synthesis of the two types of GOx-immobilized MNPs were described, thus emphasizing the difference between the two reagents. Scanning Electron Microscopy and Dynamic Light Scattering were used for size, shape and colloidal stability characterization of the pristine MNPs and of those coupled with GOx. Binding of GOx to MNPs by using GA or SA was confirmed by FT-IR spectroscopy. The stability of the immobilized and free enzyme was investigated by measuring the enzymatic activity. The study confirmed that the resulting activity of the immobilized enzyme and the optimization of enzyme immobilization depended on the type of reagent used and duration of the process. The catalytic performance of immobilized enzyme was tested, revealing that the long-term colloidal stability of SA-functionalized MNPs was superior to those prepared with GA. In conclusion, the SA-functionalized bioconjugates have a better potential as compared to the GA-modified nanosystems to be regarded as catalytic nanodevices for biomedical purposes such as biosensors.

New Physical Hydrogels Based on Co-Assembling of FMOC-Amino Acids.

In the last years, physical hydrogels have been widely studied due to the characteristics of these structures, respectively the non-covalent interactions and the absence of other necessary components for the cross-linking processes. Low molecular weight gelators are a class of small molecules which form higher ordered structures through hydrogen bonding and π-π interactions. In this context it is known that the formation of hydrogels based on FMOC-amino acids is determined by the primary structures of amino acids and the secondary structure arrangement (alpha-helix or beta-sheet motifs). The present study aimed to obtain supramolecular gels through co-assembly phenomenon using FMOC-amino acids as low molecular weight gelators. The stability of the new structures was evaluated by the vial inversion test, while FTIR spectra put into evidence the interaction between the compounds. The gel-like structure is evidenced by viscoelastic parameters in oscillatory shear conditions. SEM microscopy was used to obtain the visual insight into the morphology of the physical hydrogel network while DLS measurements highlighted the sol-gel transition. The molecular arrangement of gels was determined by circular dichroism, fluorescence and UV-Vis spectroscopy.