Organic Chemicals from Wood: Selective Depolymerization and Dearomatization of Lignin via Aqueous Electrocatalysis.

Replacing crude oil as the primary industrial source of carbon-based chemicals has become crucial for both environmental and resource sustainability reasons. In this scenario, wood arises as an excellent candidate, whilst depolymerization approaches have emerged as promising strategies to unlock the lignin potential as a resource in the production of high-value organic chemicals. However, many drawbacks, such as toxic solvents, expensive catalysts, high energy inputs, and poor product selectivity have represented major challenges to this task. Herein, we present an unprecedented approach using electrocatalysis for the simultaneous depolymerization and dearomatization of lignin in aqueous medium under ambient conditions. By employing water/sodium carbonate as a solvent system, we demonstrated a pathway for selectively depolymerizing lignin under reductive electrochemical conditions using carbon as an electrocatalyst. After reductive electrocatalysis, the presence of aromatic compounds was no longer detected via nuclear magnetic resonance (NMR) spectroscopy. Further characterization by NMR, FTIR spectroscopy, and mass spectrometry revealed the major presences of sodium levulinate, sodium 4-hydroxyvalerate, sodium formate, and sodium acetate as products. By achieving a complete dearomatization, valuable aliphatic intermediates with enhanced reactivity were selectively obtained, opening new avenues for further synthesis of many different organic chemicals, and contributing to a more sustainable and circular economy.

MoS2 nanoflower-decorated lignin nanoparticles for superior lubricant properties.

Lignin has been, for a long time, treated as a low-value waste product. To change this scenario, high-value applications have been recently pursued, e.g., the preparation of hybrid materials with inorganic components. Although hybrid inorganic-based materials can benefit from the reactive lignin phenolic groups at the interface, often responsible for optimizing specific properties, this is still an underexplored field. Here, we present a novel and green material based on the combination of hydroxymethylated lignin nanoparticles (HLNPs) with molybdenum disulfide (MoS2) nanoflowers grown via a hydrothermal route. By bringing together the lubricant performance of MoS2 and the structural stability of biomass-based nanoparticles, a MoS2-HLNPs hybrid is presented as a bio-derived additive for superior tribological performances. While FT-IR analysis confirmed the structural stability of lignin after the hydrothermal growth of MoS2, TEM and SEM micrographs revealed a homogeneous distribution of MoS2 nanoflowers (average size of 400 nm) on the HLNPs (average size of 100 nm). Regarding the tribological tests, considering a pure oil as reference, only HLNPs as bio-derived additives led to a reduction in the wear volume of 18%. However, the hybrid of MoS2-HLNPs led to a considerably higher reduction (71%), pointing out its superior performance. These results open a new window of opportunity for a versatile and yet underexplored field that can pave the way for a new class of biobased lubricants.

Electrochemical Depolymerization of Lignin in a Biomass-based Solvent.

Invited for this month's cover is the group of Adam Slabon at the University of Wuppertal. The image illustrates the reductive depolymerization of lignin into monomers using copper as electrocatalyst. The Research Article itself is available at 10.1002/cssc.202200718.

Electrochemical Depolymerization of Lignin in a Biomass-based Solvent.

Breaking down lignin into smaller units is the key to generate high value-added products. Nevertheless, dissolving this complex plant polyphenol in an environment-friendly way is often a challenge. Levulinic acid, which is formed during the hydrothermal processing of lignocellulosic biomass, has been shown to efficiently dissolve lignin. Herein, levulinic acid was evaluated as a medium for the reductive electrochemical depolymerization of the lignin macromolecule. Copper was chosen as the electrocatalyst due to the economic feasibility and low activity towards the hydrogen evolution reaction. After depolymerization, high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy revealed lignin-derived monomers and dimers. A predominance of aryl ether and phenolic groups was observed. Depolymerized lignin was further evaluated as an anti-corrosion coating, revealing enhancements on the electrochemical stability of the metal. Via a simple depolymerization process of biomass waste in a biomass-based solvent, a straightforward approach to produce high value-added compounds or tailored biobased materials was demonstrated.

Curcuminoid-Tailored Interfacial Free Energy of Hydrophobic Fibers for Enhanced Biological Properties.

The ability of mimicking the extracellular matrix architecture has gained electrospun scaffolds a prominent space into the tissue engineering field. The high surface-to-volume aspect ratio of nanofibers increases their bioactivity while enhancing the bonding strength with the host tissue. Over the years, numerous polyesters, such as poly(lactic acid) (PLA), have been consolidated as excellent matrices for biomedical applications. However, this class of polymers usually has a high hydrophobic character, which limits cell attachment and proliferation, and therefore decreases biological interactions. In this way, functionalization of polyester-based materials is often performed in order to modify their interfacial free energy and achieve more hydrophilic surfaces. Herein, we report the preparation, characterization, and in vitro assessment of electrospun PLA fibers with low contents (0.1 wt %) of different curcuminoids featuring π-conjugated systems, and a central ß-diketone unit, including curcumin itself. We evaluated the potential of these materials for photochemical and biomedical purposes. For this, we investigated their optical properties, water contact angle, and surface features while assessing their in vitro behavior using SH-SY5Y cells. Our results demonstrate the successful generation of homogeneous and defect-free fluorescent fibers, which are noncytotoxic, exhibit enhanced hydrophilicity, and as such greater cell adhesion and proliferation toward neuroblastoma cells. The unexpected tailoring of the scaffolds' interfacial free energy has been associated with the strong interactions between the PLA hydrophobic sites and the nonpolar groups from curcuminoids, which indicate its role for releasing hydrophilic sites from both parts. This investigation reveals a straightforward approach to produce photoluminescent 3D-scaffolds with enhanced biological properties by using a polymer that is essentially hydrophobic combined with the low contents of photoactive and multifunctional curcuminoids.

The role of nanohydroxyapatite on the morphological, physical, and biological properties of chitosan nanofibers.

OBJECTIVES: This study aimed to evaluate the effects of nanohydroxyapatite (nHAp) particles on the morphological, chemical, physical, and biological properties of chitosan electrospun nanofibers. MATERIALS AND METHODS: nHAp particles with a 1.67 Ca/P ratio were synthesized via the aqueous precipitation method, incorporated into chitosan polymer solution (0.5 wt%), and electrospun into nHAp-loaded fibers (ChHa fibers). Neat chitosan fibers (nHAp-free, Ch fibers) were used as the control. The electrospun fiber mats were characterized using morphological, topographical, chemical, thermal, and a range of biological (antibacterial, antibiofilm, cell viability, and alkaline phosphatase [ALP] activity) analyses. Data were analyzed using ANOVA and Tukey's test (α = 0.05). RESULTS: ChHa fibers demonstrated a bead-like morphology, with thinner (331 ± 110 nm) and smoother (Ra = 2.9 ± 0.3 µm) distribution as compared to the control fibers. Despite showing similar cell viability and ALP activity to Ch fibers, the ChHa fibers demonstrated greater antibacterial potential against most tested bacteria (except for P. intermedia), and higher antibiofilm activity against P. gingivalis biofilm. CONCLUSIONS: The incorporation of nHAp particles did not jeopardize the overall morphology, topography, physical, and biological characteristics of the chitosan nanofibers. CLINICAL RELEVANCE: The combination of nHAp particles with chitosan can be used to engineer bioactive, electrospun composite nanofibers with potential applications in regenerative dentistry.

A novel decellularization method to produce brain scaffolds.

Scaffolds composed of extracellular matrix (ECM) can assist tissue remodeling and repair following injury. The ECM is a complex biomaterial composed of proteins, glycoproteins, proteoglycans, and glycosaminoglycans, secreted by cells. The ECM contains fundamental biological cues that modulate cell behavior and serves as a structural scaffold for cell adhesion and growth. For clinical applications, where immune rejection is a constraint, ECM can be processed using decellularization methods intended to remove cells and donor antigens from tissue or organs, while preserving native biological cues essential for cell growth and differentiation. Recent studies show bioengineered organs composed by a combination of a diversity of materials and stem cells as a possibility of new therapeutic strategies to treat diseases that affect different tissues and organs, including the central nervous system (CNS). Nevertheless, the methodologies currently described for brain decellularization involve the use of several chemical reagents with many steps that ultimately limit the process of organ or tissue recellularization. Here, we describe for the first time a fast and straightforward method for complete decellularization of mice brain by the combination of rapid freezing and thawing following the use of only one detergent (Sodium dodecyl sulfate (SDS)). Our data show that using the protocol we describe here, the brain was entirely decellularized, while still maintaining ECM components that are essential for cell survival on the scaffold. Our results also show the cell-loading of the decellularized brain matrix with Neuro2a cells, which were identified by immunohistochemistry in their undifferentiated form. We conclude that this novel and simple method for brain decellularization can be used as a scaffold for cell-loading.

Polypyrrole increases branching and neurite extension by Neuro2A cells on PBAT ultrathin fibers.

We present a methodology for production and application of electrospun hybrid materials containing commercial polyester (poly (butylene adipate-co-terephthalate; PBAT), and a conductive polymer (polypyrrole; PPy) as scaffold for neuronal growth and differentiation. The physical-chemical properties of the scaffolds and optimization of the electrospinning parameters are presented. The electrospun scaffolds are biocompatible and allow proper adhesion and spread of mesenchymal stem cells (MSCs). Fibers produced with PBAT with or without PPy were used as scaffold for Neuro2a mouse neuroblastoma cells adhesion and differentiation. Neuro2a adhered to PBAT and PBAT/PPy2% scaffolds without laminin coating. However, Neuro2a failed to differentiate in PBAT when stimulated by treatment with retinoic acid (RA), but differentiated in PBAT/PPy2% fibers. We hypothesize that PBAT hydrophobicity inhibited proper spreading and further differentiation, and inhibition was overcome by coating the PBAT fibers with laminin. We conclude that fibers produced with the combination of PBAT and PPy can support neuronal differentiation.

Nanohydroxyapatite/Graphene Nanoribbons Nanocomposites Induce in Vitro Osteogenesis and Promote in Vivo Bone Neoformation.

Nanomaterials based on graphene oxide nanoribbons (GNR) and nanohydroxyapatite (nHAp) serve as attractive materials for bone tissue engineering. Herein, we evaluated the potential of nHAp/GNR toward in vitro analysis of specific genes related to osteogenesis and in vivo bone regeneration using animal model. Three different concentrations of nHAp/GNR composites were analyzed in vitro using a cytotoxicity assay, and osteogenic potential was determined by ALP, OPN, OCN, COL1, and RUNX2 genes and alkaline phosphatase assays. In vivo bone neoformation using a well-established in vivo rat tibia defect model was used to confirm the efficiency of the optimized composite. The scaffolds were nontoxic, and the osteogenesis process was dose-dependent (at 200 µg mL-1 of nHAp/GNR) compared to controls. The in vivo results showed higher bone neoformation after 15 days of nHAp/GNR implantation compared to all groups. After 21 days, both nHAp/GNR composites showed better lamellar bone formation compared to control. We attributed this enhanced bone neoformation to the high bioactivity and surface area presented by nHAp/GNR composites, which was systematically evaluated in previous studies. These new in vivo results suggest that nHAp/GNR composites can be exploited for a range of strategies for the improved development of novel dental and orthopedic bone grafts to accelerate bone regeneration.

Electrospun ultrathin PBAT/nHAp fibers influenced the in vitro and in vivo osteogenesis and improved the mechanical properties of neoformed bone.

Combining polyester scaffolds with synthetic nanohydroxyapatite (nHAp), which is bioactive and osteoconductive, is a plausible strategy to improve bone regeneration. Here, we propose the combination of PBAT [poly(butylene-adipate-co-terephthalate)] and synthetic nHAp (at 3 and 5wt%). PBAT is a relatively a new polymer with low crystallinity and attractive biodegradability and mechanical properties for orthopedic applications, however, with a still underexplored potential for in vivo applications. Then, we performed a careful biological in vitro and in vivo set of experiments to evaluate the influence of PBAT containing two different nHAp loads. For in vitro assays, osteoblast-like MG63 cells were used and the bioactivity and gene expression related to osteogenesis were evaluated by qRT-PCR. For in vivo experiments, twenty-four male rats were used and a tibial defect model was applied to insert the scaffolds. Micro-computed tomography (Micro-CT) and histological analysis were used to assess e bone neoformation after 6 weeks of implantation. Three point flexural tests measured the mechanical properties of the neoformed bone. All scaffolds showed promising in vitro properties, since they were not cytotoxic against MG-63 cells and promoted high cell proliferation and formation of mineralized nodules. From a mechanistic point-of-view, nHAp loading increased hydrophilicity, which in turn allowed for a better adsorption of proteins and consequent changes in the phenotypic expression of osteoblasts. nHAp induced better cellular responses on/in the scaffolds, which was mainly attributed to its osteoconductive and osteoinductive properties. Micro-CT images showed that nHAp at 3% and 5wt% led to more effective bone formation, presenting the highest bone volume after 6 weeks of implantation. Considering the three point flexural tests, 5wt% of nHAp positively influenced the flexural mode of the neoformed bone, but the stiffiness was similar between the 3% and 5wt% groups. In summary, this investigation demonstrated great potential for the application of these novel scaffolds towards bone regeneration and, thus, should be further studied.

PDLLA honeycomb-like scaffolds with a high loading of superhydrophilic graphene/multi-walled carbon nanotubes promote osteoblast in vitro functions and guided in vivo bone regeneration.

Herein, we developed honeycomb-like scaffolds by combining poly (d, l-lactic acid) (PDLLA) with a high amount of graphene/multi-walled carbon nanotube oxides (MWCNTO-GO, 50% w/w). From pristine multi-walled carbon nanotubes (MWCNT) powders, we produced MWCNTO-GO via oxygen plasma etching (OPE), which promoted their exfoliation and oxidation. Initially, we evaluated PDLLA and PDLLA/MWCNTO-GO scaffolds for tensile strength tests, cell adhesion and cell viability (with osteoblast-like MG-63 cells), alkaline phosphatase (ALP, a marker of osteoblast differentiation) activity and mineralized nodule formation. In vivo tests were carried out using PDLLA and PDLLA/MWCNTO-GO scaffolds as fillers for critical defects in the tibia of rats. MWCNTO-GO loading was responsible for decreasing the tensile strength and elongation-at-break of PDLLA scaffolds, although the high mechanical performance observed (~600MPa) assures their application in bone tissue regeneration. In vitro results showed that the scaffolds were not cytotoxic and allowed for osteoblast-like cell interactions and the formation of mineralized matrix nodules. Furthermore, MG-63 cells grown on PDLLA/MWCNTO-GO significantly enhanced osteoblast ALP activity compared to controls (cells alone), while the PDLLA group showed similar ALP activity when compared to controls and PDLLA/MWCNTO-GO. Most impressively, in vivo tests suggested that compared to PDLLA scaffolds, PDLLA/MWCNTO-GO had a superior influence on bone cell activity, promoting greater new bone formation. In summary, the results of this study highlighted that this novel scaffold (MWCNTO-GO, 50% w/w) is a promising alternative for bone tissue regeneration and, thus, should be further studied.

Magnetic super-hydrophilic carbon nanotubes/graphene oxide composite as nanocarriers of mesenchymal stem cells: Insights into the time and dose dependences.

Among nanostructured materials, multi-walled carbon nanotubes (MWCNT) have demonstrated great potential for biomedical applications in recent years. After oxygen plasma etching, we can obtain super-hydrophilic MWCNT that contain graphene oxide (GO) at their tips. This material exhibits good dispersion in biological systems due to the presence of polar groups and its excellent magnetic properties due to metal particle residues from the catalyst that often remain trapped in its walls and tips. Here, we show for the first time a careful biological investigation using magnetic superhydrophilic MWCNT/GO (GCN composites). The objective of this study was to investigate the application of GCN for the in vitro immobilization of mesenchymal stem cells. Our ultimate goal was to develop a system to deliver mesenchymal stem cells to different tissues and organs. We show here that mesenchymal stem cells were able to internalize GCN with a consequent migration when subjected to a magnetic field. The cytotoxicity of GCN was time- and dose-dependent. We also observed that GCN internalization caused changes in the gene expression of the proteins involved in cell adhesion and migration, such as integrins, laminins, and the chemokine CXCL12, as well as its receptor CXCR4. These results suggest that GCN represents a potential new platform for mesenchymal stem cell immobilization at injury sites.

Influence of low contents of superhydrophilic MWCNT on the properties and cell viability of electrospun poly (butylene adipate-co-terephthalate) fibers.

The use of poly (butylene adipate-co-terephthalate) (PBAT) in tissue engineering, more specifically in bone regeneration, has been underexplored to date due to its poor mechanical resistance. In order to overcome this drawback, this investigation presents an approach into the preparation of electrospun nanocomposite fibers from PBAT and low contents of superhydrophilic multi-walled carbon nanotubes (sMWCNT) (0.1-0.5wt.%) as reinforcing agent. We employed a wide range of characterization techniques to evaluate the properties of the resulting electrospun nanocomposites, including Field Emission Scanning Electronic Microscopy (FE-SEM), Transmission Electronic Microscopy (TEM), tensile tests, contact angle measurements (CA) and biological assays. FE-SEM micrographs showed that while the addition of sMWCNT increased the presence of beads on the electrospun fibers' surfaces, the increase of the neat charge density due to their presence reduced the fibers' average diameter. The tensile test results pointed that sMWCNT acted as reinforcement in the PBAT electrospun matrix, enhancing its tensile strength (from 1.3 to 3.6MPa with addition of 0.5wt.% of sMWCNT) and leading to stiffer materials (lower elongation at break). An evaluation using MG63 cells revealed cell attachment into the biomaterials and that all samples were viable for biomedical applications, once no cytotoxic effect was observed. MG-63 cells osteogenic differentiation, measured by ALP activity, showed that mineralized nodules formation was increased in PBAT/0.5%CNTs when compared to control group (cells). This investigation demonstrated a feasible novel approach for producing electrospun nanocomposites from PBAT and sMWCNT with enhanced mechanical properties and adequate cell viability levels, which allows for a wide range of biomedical applications for these materials.

Bio-based Films from Linter Cellulose and Its Acetates: Formation and Properties.

This paper describes the results obtained on the preparation of films composed of linter cellulose and the corresponding acetates. The acetylation was carried out in the LiCl/DMAc solvent system. Films were prepared from a LiCl/DMAc solution of cellulose acetates (degree of substitution, DS 0.8-2.9) mixed with linter cellulose (5, 10 and 15 wt %). Detailed characterization of the films revealed the following: (i) they exhibited fibrous structures on their surfaces. The strong tendency of the linter cellulose chains to aggregate in LiCl/DMAc suggests that these fibrous elements consist of cellulose chains, as can be deduced from SEM images of the film of cellulose proper; (ii) the cellulose acetate films obtained from samples with DS 2.1 and 2.9 exhibited microspheres on the surface, whose formation seems to be favored for acetates with higher DS; (iii) AFM analysis showed that, in general, the presence of cellulose increased both the asperity thickness and the surface roughness of the analyzed films, indicating that cellulose chains are at least partially organized in domains and not molecularly dispersed between acetate chains; and (iv) the films prepared from cellulose and acetates exhibited lower hygroscopicity than the acetate films, also suggesting that the cellulose chains are organized into domains, probably due to strong intermolecular interactions. The linter and sisal acetates (the latter from a prior study), and their respective films, were prepared using the same processes; however, the two sets of films presented more differences (as in humidity absorption, optical, and tensile properties) than similarities (as in some morphological aspects), most likely due to the different properties of the starting materials. Potential applications of the films prepared in tissue engineering scaffold coatings and/or drug delivery are mentioned.