Injectable Antioxidant and Oxygen-Releasing Lignin Composites to Promote Wound Healing.

The application of engineered biomaterials for wound healing has been pursued since the beginning of tissue engineering. Here, we attempt to apply functionalized lignin to confer antioxidation to the extracellular microenvironments of wounds and to deliver oxygen from the dissociation of calcium peroxide for enhanced vascularization and healing responses without eliciting inflammatory responses. Elemental analysis showed 17 times higher quantity of calcium in the oxygen-releasing nanoparticles. Lignin composites including the oxygen-generating nanoparticles released around 700 ppm oxygen per day at least for 7 days. By modulating the concentration of the methacrylated gelatin, we were able to maintain the injectability of lignin composite precursors and the stiffness of lignin composites suitable for wound healing after photo-cross-linking. In situ formation of lignin composites with the oxygen-releasing nanoparticles enhanced the rate of tissue granulation, the formation of blood vessels, and the infiltration of α-smooth muscle actin+ fibroblasts into the wounds over 7 days. At 28 days after surgery, the lignin composite with oxygen-generating nanoparticles remodeled the collagen architecture, resembling the basket-weave pattern of unwounded collagen with minimal scar formation. Thus, our study shows the potential of functionalized lignin for wound-healing applications requiring balanced antioxidation and controlled release of oxygen for enhanced tissue granulation, vascularization, and maturation of collagen.

Tailoring Physical Properties of Dual-Network Acrylamide Hydrogel Composites by Engineering Molecular Structures of the Cross-linked Network.

We demonstrate the impact of engineering molecular structures of poly(acrylamide) (PAAm) and poly(N-isopropylacrylamide) (PNIPAm) hydrogel composites on several physical properties. The network structure was systematically varied by (i) the type and the concentration of difunctional cross-linkers and (ii) the type of native or chemically modified natural polymers, including sodium alginate, methacrylate/dopamine-incorporated porcine skin gelatin and fish skin gelatin, and thiol-incorporated lignosulfonate, which are attractive biopolymers generated in pulp and food industries because of their abundance, rich chemical functionalities, and environmental friendliness. First, we added cross-linking agents of varying lengths at different concentrations to assess how the cross-linking agent modulates the mechanical properties of acrylamide-based composites with alginate. After chemically modifying gelatins from fish or porcine skin with methacrylate and/or dopamine, the acrylamide-based composites were fabricated with the chemically modified gelatins and thiolated lignosulfonate to assess the stress-strain behavior. Furthermore, swelling ratios were measured with respect to temperature change. The mechanical properties were systematically modulated by the changes in the molecular structure, that is, the length of the chemical unit between two end alkene groups in the difunctional cross-linker and the types of the additive natural polymers. Overall, PAAm hydrogel composites exhibit a significant, negative correlation between toughness and the volume fraction of the swollen state and between strain at fracture and the volume fraction of the swollen state. In contrast, PNIPAm hydrogel composites showed positive, but only moderate correlations, which is attributed to the difference in the network polymer structure.

Reactive oxygen species scavenging nanofibers with chitosan-stabilized Prussian blue nanoparticles for enhanced wound healing efficacy.

Chronic inflammatory wounds pose therapeutic challenges in the biomedical field. Polymeric nanofibrous matrices provide extracellular-matrix-like structures to facilitate wound healing; however, wound infection and the subsequent accumulation of reactive oxygen species (ROS) delay healing. Therefore, we herein developed electrospun nanofibers (NFs), composed of chitosan-stabilized Prussian blue (PBChi) nanoparticles (NPs) and poly(vinyl alcohol) (PVA), with ROS scavenging activity to impart antioxidant and wound healing properties. The PBChi NPs were prepared using chitosan with different molecular weights, and their weight ratio with respect to PVA was optimized to yield PBChi-NP-coated PVA NFs with well-defined NF structures. In situ and in vitro antioxidant activity assays showed that the PBChi/PVA NFs could effectively remove ROS. Particularly, PBChi/PVA NFs with a lower chitosan molecular weight exhibited greater antioxidant activity. The hydroxyl radical scavenging activity of PBChi10k/PVA NFs was 60.4 %, approximately two-fold higher than that of PBChi100k/PVA NFs. Further, at the concentration of 10 µg/mL, they could significantly lower the in vitro ROS level by up to 50.7 %. The NFs caused no significant reduction in cell viability, owing to the excellent biocompatibility of PVA with PBChi NPs. Treatment using PBChi/PVA NFs led to faster cell proliferation in in vitro scratch wounds, reducing their size from 202 to 162 µm. The PBChi/PVA NFs possess notable antioxidant and cell proliferation properties as ROS-scavenging wound dressings.

Rational Process Design for Facile Fabrication of Dual Functional Hybrid Membrane of MOF and Electrospun Nanofiber towards High Removal Efficiency of PM2.5 and Toxic Gases.

The application of nanofiber (NF) and porous metal-organic framework (MOF) has increasingly attracted attention for the protection of public health. This composite platform provides the physical sieving of particulate matters (PMs) and capturing gases, serving as an outstanding filtering medium with lightweight and multifunctionality. Herein, process design and optimization are performed to produce a multifunctional membrane comprised NFs and MOF particles. Electrospinning/electrospray techniques are used to fabricate a hybrid membrane of poly(vinyl alcohol) NF and Fe-BTC as an adsorptive MOF on a macroporous nonwoven (NW). Three types of filters are prepared by varying the order of processing steps, that is, MOF/NF/NW, MOF+NF/NW, and NF/MOF/NW, to elucidate the effect of the fabrication process in the filtration of air pollutant. The optimal filtration performance is achieved in MOF+NF/NW system: the highest filtration efficiency (97%) and outstanding gas capturing efficiencies (≈60% and ≈35% decreases from initial NH3 and H2 S concentrations, respectively). However, when air permeability and filtration efficiency are considered, the most desirable configuration for personal protection equipment (PPE) is NF/MOF/NW system, which effectively enabled comfortable breathing without compromising the lightweight and multifunctional performance.

Attenuating Fibrotic Markers of Patient-Derived Dermal Fibroblasts by Thiolated Lignin Composites.

We report the use of phenolic functional groups of lignosulfonate to impart antioxidant properties and the cell binding domains of gelatin to enhance cell adhesion for poly(ethylene glycol) (PEG)-based scaffolds. Chemoselective thiol-ene chemistry was utilized to form composites with thiolated lignosulfonate (TLS) and methacrylated fish gelatin (fGelMA). Antioxidant properties of TLS were not altered after thiolation and the levels of antioxidation were comparable to those of L-ascorbic acid. PEG-fGelMA-TLS composites significantly reduced the difference in COL1A1, ACTA2, TGFB1, and HIF1A genes between high-scarring and low-scarring hdFBs, providing the potential utility of TLS to attenuate fibrotic responses.

Multistimuli-Responsive Optical Hydrogel Nanomembranes to Construct Planar Color Display Boards for Detecting Local Environmental Changes.

Planar metal-insulator-metal (MIM) optical cavities are attractive for biochemical and environmental sensing applications, as they offer a cost-effective cavity platform with acceptable performances. However, localized detection and scope of expansion of applicable analytes are still challenging. Here, we report a stimuli-responsive color display board that can exhibit local spectral footprints, for locally applied heat and alcohol presence. A thermoresponsive, optically applicable, and patternable copolymer, poly(N-isopropylacrylamide-r-glycidyl methacrylate), is synthesized and used with a photosensitive cross-linker to produce a responsive insulating layer. This layer is then sandwiched between two nanoporous silver membranes to yield a thermoresponsive MIM cavity. The resonant spectral peak is blue-shifted as the environmental temperature increases, and the dynamic range of the resonant peak is largely affected by the composition and structure of the cross-linker and the copolymer. The localized temperature increase of silk particles with gold nanoparticles by laser heating can be measured by reading the spectral shift. In addition, a free-standing color board can be transferred onto a curved biological tissue sample, allowing us to simultaneously read the temperature of the tissue sample and the concentration of ethanol. The stimuli-responsive MIM provides a new way to optically sense localized environmental temperature and ethanol concentration fluctuations.

Electrospinning/Electrospray of Ferrocene Containing Copolymers to Fabricate ROS-Responsive Particles and Fibers.

We demonstrate an electrospray/electrospinning process to fabricate stimuli-responsive nanofibers or particles that can be utilized as stimuli-responsive drug-loaded materials. A series of random copolymers consisting of hydrophobic ferrocene monomers and hydrophilic carboxyl groups, namely poly(ferrocenylmethyl methacrylate-r-methacrylic acid) [poly(FMMA-r-MA)] with varied composition, was synthesized with free radical copolymerization. The morphologies of the resulting objects created by electrospray/electrospinning of the poly(FMMA-r-MA) solutions were effectively varied from particulate to fibrous structures by control of the composition, suggesting that the morphology of electrosprayed/electrospun copolymer objects was governed by its composition and hence, interaction with the solvent, highlighting the significance of the balance of hydrophilicity/hydrophobicity of the copolymer chain to the assembled structure. Resulting particles and nanofibers exhibited largely preserved responsiveness to reactive oxygen species (ROS) during the deposition process, opening up the potential to fabricate ROS-sensitive material with various desirable structures toward different applications.

X-ray-Based Spectroscopic Techniques for Characterization of Polymer Nanocomposite Materials at a Molecular Level.

This review provides detailed fundamental principles of X-ray-based characterization methods, i.e., X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, and near-edge X-ray absorption fine structure, and the development of different techniques based on the principles to gain deeper understandings of chemical structures in polymeric materials. Qualitative and quantitative analyses enable obtaining chemical compositions including the relative and absolute concentrations of specific elements and chemical bonds near the surface of or deep inside the material of interest. More importantly, these techniques help us to access the interface of a polymer and a solid material at a molecular level in a polymer nanocomposite. The collective interpretation of all this information leads us to a better understanding of why specific material properties can be modulated in composite geometry. Finally, we will highlight the impacts of the use of these spectroscopic methods in recent advances in polymer nanocomposite materials for various nano- and bio-applications.