Supramolecular Mimotope Peptide Nanofibers Promote Antibody-Ligand Polyvalent and Instantaneous Recognition for Biopharmaceutical Analysis.

Peptide-based supramolecules exhibit great potential in various fields due to their improved target recognition ability and versatile functions. However, they still suffer from numerous challenges for the biopharmaceutical analysis, including poor self-assembly ability, undesirable ligand-antibody binding rates, and formidable target binding barriers caused by ligand crowding. To tackle these issues, a "polyvalent recognition" strategy employing the CD20 mimotope peptide derivative NBD-FFVLR-GS-WPRWLEN (acting on the CDR domains of rituximab) was proposed to develop supramolecular nanofibers for target antibody recognition. These nanofibers exhibited rapid self-assembly within only 1 min and robust stability. Their binding affinity (179 nM) for rituximab surpassed that of the monomeric peptide (7 µM) by over 38-fold, highlighting that high ligand density and potential polyvalent recognition can efficiently overcome the target binding barriers of traditional supramolecules. Moreover, these nanofibers exhibited an amazing "instantaneous capture" rate (within 15 s), a high recovery (93 ± 3%), and good specificity for the target antibody. High-efficiency enrichment of rituximab was achieved from cell culture medium with good recovery and reproducibility. Intriguingly, these peptide nanofibers combined with bottom-up proteomics were successful in tracking the deamidation of asparagine 55 (from 10 to 16%) on the rituximab heavy chain after 21 day incubation in human serum. In summary, this study may open up an avenue for the development of versatile mimotope peptide supramolecules for biorecognition and bioanalysis of biopharmaceuticals.

Pleiotropic Nanostructures Built from l-Histidine Show Biologically Relevant Multicatalytic Activities.

The essential amino acid histidine plays a central role in the manifestation of several metabolic processes, including protein synthesis, enzyme-catalysis, and key biomolecular interactions. However, excess accumulation of histidine causes histidinemia, which shows brain-related medical complications, and the molecular mechanism of such histidine-linked complications is largely unknown. Here, we show that histidine undergoes a self-assembly process, leading to the formation of amyloid-like cytotoxic and catalytically active nanofibers. The kinetics of histidine self-assembly was favored in the presence of Mg(II) and Co(II) ions. Molecular dynamics data showed that preferential noncovalent interactions dominated by H-bonds between histidine molecules facilitate the formation of histidine nanofibers. The histidine nanofibers induced amyloid cross-seeding reactions in several proteins and peptides including pathogenic Aß1-42 and brain extract components. Further, the histidine nanofibers exhibited oxidase activity and enhanced the oxidation of neurotransmitters. Cell-based studies confirmed the cellular internalization of histidine nanofibers in SH-SY5Y cells and subsequent cytotoxic effects through necrosis and apoptosis-mediated cell death. Since several complications including behavioral abnormality, developmental delay, and neurological disabilities are directly linked to abnormal accumulation of histidine, our findings provide a foundational understanding of the mechanism of histidine-related complications. Further, the ability of histidine nanofibers to catalyze amyloid seeding and oxidation reactions is equally important for both biological and materials science research.

Patterned PCL/PGS Nanofibrous Hyaluronic Acid-Coated Scaffolds Promote Cellular Response and Modulate Gene Expression Profiles.

Chronic wounds impose a significant burden on individuals and healthcare systems, necessitating the development of advanced wound management strategies. Tissue engineering, with its ability to create scaffolds that mimic native tissue structures and promote cellular responses, offers a promising approach. Electrospinning, a widely used technique, can fabricate nanofibrous scaffolds for tissue regeneration. In this study, we developed patterned nanofibrous scaffolds using a blend of poly(ε-caprolactone) (PCL) and poly(glycerol sebacate) (PGS), known for their biocompatibility and biodegradability. By employing a mesh collector, we achieved a unique fiber orientation pattern that emulated the natural tissue architecture. The average fiber diameter of PGS/PCL collected on aluminum foil and on mesh was found to be 665.2 ± 4 and 404.8 ± 16 nm, respectively. To enhance the scaffolds' bioactivity and surface properties, it was coated with hyaluronic acid (HA), a key component of the extracellular matrix known for its wound-healing properties. The HA coating improved the scaffold hydrophilicity and surface wettability, facilitating cell attachment, spreading, and migration. Furthermore, the HA-coated scaffold exhibited enhanced biocompatibility, promoting cell viability and proliferation. High-throughput RNA sequencing was performed to analyze the influence of the fabricated scaffold on the gene expression levels of endothelial cells. The top-upregulated biological processes and pathways include cell cycle regulation and cell proliferation. The results revealed significant alterations in gene expression profiles, indicating the scaffold's ability to modulate cellular functions and promote wound healing processes. The developed scaffold holds great promise for advanced wound management and tissue regeneration applications. By harnessing the advantages of aligned nanofibers, biocompatible polymers, and HA coating, this scaffold represents a potential solution for improving wound healing outcomes and improving the quality of life for individuals suffering from chronic wounds.

Transmucosal Delivery of Peptides and Proteins Through Nanofibers: Current Status and Emerging Developments.

Advancements in recombinant DNA technology have made proteins and peptides available for diagnostic and therapeutic applications, but their effectiveness when taken orally leads to poor patient compliance, requiring clinical administration. Among the alternative routes, transmucosal delivery has the advantage of being noninvasive and bypassing hepato-gastrointestinal clearance. Various mucosal routes-buccal, nasal, pulmonary, rectal, and vaginal-have been explored for delivering these macromolecules. Nanofibers, due to their unique properties like high surface-area-to-volume ratio, mechanical strength, and improved encapsulation efficiency, serve as promising carriers for proteins and peptides. These nanofibers can be tailored for quick dissolution, controlled release, enhanced encapsulation, targeted delivery, and improved bioavailability, offering superior pharmaceutical and pharmacokinetic performance compared to conventional methods. This leads to reduced dosages, fewer side effects, and enhanced patient compliance. Hence, nanofibers hold tremendous potential for protein/peptide delivery, especially through mucosal routes. This review focuses on the therapeutic application of proteins and peptides, challenges faced in their conventional delivery, techniques for fabricating different types of nanofibers and, various nanofiber-based dosage forms, and factors influencing nanofiber generation. Insights pertaining to the precise selection of materials used for fabricating nanofibers and regulatory aspects have been covered. Case studies wherein the use of specific protein/peptide-loaded nanofibers and delivered via oral/vaginal/nasal mucosa for diagnostic/therapeutic use and related preclinical and clinical studies conducted have been included in this review.

Self-assembly of amphiphilic helical-coiled peptide nanofibers and inhibition of fibril formation with curcumin.

Amphiphilic peptide sequences are conducive to secondary structures that self-assemble into higher-ordered peptide nanostructures. A select set of amphiphilic polycationic peptides displayed stable helical-coiled structures that self-assembled into peptide nanofibers. The progression of peptide fibril formation revealed short protofibrils that extended into thin filaments and into an entangled network of nanofibers over an extended (5 days) incubation period. Ligand binding with 8-anilinonaphthalene-1-sulfonic acid (ANS) and Congo Red (CR) confirmed the amphiphilic helical-coiled peptide structure assembly into nanofibers, whereas curcumin treatment led to inhibition of fibril formation. Considering the vast repertoire of fibrous biomaterials and peptide or protein (mis)folding contingent on fibril formation, this work relates the molecular interplay in between sequence composition, structural folding and the ligand binding events impacting peptide self-assembly into nanofibers.

Synergistic activation of lamellar bismuth selenide anchored functionalized carbon nanofiber for detecting hazardous carbendazim in environmental water samples.

Pesticides pollute natural water reservoirs through persistent accumulation. Therefore, their toxicity and degradability are serious issues. Carbendazim (CBZ) is a pesticide used against fungal infections in agricultural crops, and its overexploitation detrimentally affects aquatic ecosystems and organisms. It is necessary to design a logical, efficient, and field-deployable method for monitoring the amount of CBZ in environmental samples. Herein, a nano-engineered bismuth selenide (Bi2Se3)/functionalized carbon nanofiber (f-CNF) nanocomposite was utilized as an electrocatalyst to fabricate an electrochemical sensing platform for CBZ. Bi2Se3/f-CNF exhibited a substantial electroactive surface area, high electrocatalytic activity, and high conductivity owing to the synergistic interaction of Bi2Se3 with f-CNF. The structural chemical compositions and morphology of the Bi2Se3/f-CNF nanocomposite were confirmed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and field-emission scanning electron microscopy (FESEM). Electrochemical analysis was carried out using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). The voltammetry and impedance experiments exposed that the Bi2Se3/f-CNF-modified GCE has attained adequate electrocatalytic function with amended features of electron transportation (Rct = 35.93 Ω) and improved reaction sites (0.082 cm2) accessible by CBZ moiety along with exemplary electrochemical stability (98.92%). The Bi2Se3/f-CNF nanocomposite exhibited higher sensitivity of 0.2974 µA µM-1cm-2 and a remarkably low limit of detection (LOD) of 1.04 nM at a broad linera range 0.001-100 µM. The practicability of the nanocomposite was tested in environmental (tap and pond water) samples, which supports excellent signal amplification with satisfactory recoveries. Hence, the Bi2Se3/f-CNF nanocomposite is a promising electrode modifier for detecting CBZ.

Multifunctional embelin- poly (3-hydroxybutyric acid) and sodium alginate-based core-shell electrospun nanofibrous mat for wound healing applications.

In this study, coaxial electrospinning is employed to make core-shell fibers, which represents a major advance in biomaterial innovation. Fibers that combine a protective shell and a therapeutic agent-loaded core, herald a revolutionary era in tissue engineering and wound care. Besides supporting cell growth, these fibers also preserve sterility, which makes them ideal for advanced wound dressings. We used embelin as the basis for this study because of its natural antibacterial properties. Its effectiveness in inhibiting the growth of bacteria made it the ideal candidate for our research. We have synthesized core-shell nanofibers that contain Sodium Alginate (SAL) in a Poly (ethylene oxide) (PEO) shell and Embelin in a Poly (3-hydroxybutyric acid) (PHB) core, which exhibit the homogeneity and flawless structure required for biomedical applications. When using SAL-PEO and EMB-PHB solutions dissolved in 1,1,1,3,3,3 hexafluoro-2-propanol (HFIP), high consistency in results can be achieved. A biocompatibility study was conducted using NIH-3T3 fibroblasts, which demonstrated remarkable adhesion and proliferation, with over 95 % growth supporting both PHB + SAL-PEO and EMB-PHB + SAL-PEO fibers. In addition, the scaffold loaded with Embelin shows strong antibacterial activity and cytocompatibility. The combined activity demonstrates the potential of EMB-PHB + SAL-PEO fibers in wound healing, where tissue regeneration and preservation of sterility are crucial. The optimized concentration of Embelin within these scaffolds demonstrates robust antibacterial efficacy while exhibiting minimal toxicity, thus positioning them as highly promising candidates for a wide range of biological applications, including wound healing.

Unveiling Mechanobiology: A Compact Device for Uniaxial Mechanical Stimulation on Nanofiber Substrates and Its Impact on Cellular Behavior and Nanoparticle Distribution.

Biotechnology and its allied sectors, such as tissue culture, regenerative medicine, and personalized medicine, primarily rely upon extensive studies on cellular behavior and their molecular pathways for generating essential knowledge and innovative strategies for human survival. Most such studies are performed on flat, adherent, plastic-based surfaces and use nanofiber and hydrogel-like soft matrices from the past few decades. However, such static culture conditions cannot mimic the immediate cellular microenvironment, where they perceive or generate a myriad of different mechanical forces that substantially affect their downstream molecular pathways. Including such mechanical forces, still limited to specialized laboratories, using a few commercially available or noncommercial technologies are gathering increasing attention worldwide. However, large-scale consideration and adaptation by developing nations have yet to be achieved due to the lack of a cost-effective, reliable, and accessible solution. Moreover, investigations on cellular response upon uniaxial mechanical stretch cycles under more in vivo mimetic conditions are yet to be studied comprehensively. In order to tackle these obstacles, we have prepared a compact, 3D-printed device using a microcontroller, batteries, sensors, and a stepper motor assembly that operates wirelessly and provides cyclic mechanical attrition to any thin substrate. We have fabricated water-stable and stretchable nanofiber substrates with different fiber orientations by using the electrospinning technique to investigate the impact of mechanical stretch cycles on the morphology and orientation of C2C12 myoblast-like cells. Additionally, we have examined the uptake and distribution properties of BSA-epirubicin nanoparticles within cells under mechanical stimulation, which could act as fluorescently active drug-delivery agents for future therapeutic applications. Consequently, our research offers a comprehensive analysis of cellular behavior when cells are subjected to uniaxial stretching on various nanofiber mat architectures. Furthermore, we present a cost-effective alternative solution that addresses the long-standing requirement for a compact, user-friendly, and tunable device, enabling more insightful outcomes in mechanobiology.

Wound Dressing Based on Silver Nanoparticle Embedded Wool Keratin Electrospun Nanofibers Deposited on Cotton Fabric: Preparation, Characterization, Antimicrobial Activity, and Cytocompatibility.

Wool keratin (WK) protein is attractive for wound dressing and biomedical applications due to its excellent biodegradability, cytocompatibility, and wound-healing properties. In this work, WK-based wound dressings were prepared by depositing WK/poly(vinyl alcohol) (PVA) and silver nanoparticle (Ag NP)-embedded WK/PVA composite nanofibrous membranes on cotton fabrics by electrospinning. Ag NPs were biosynthesized by reduction and stabilization with sodium alginate. The formed Ag NPs were characterized by ultraviolet-visible and Fourier transform infrared (FTIR) spectroscopy, and their size was determined by transmission electron microscopy and image analysis. The formed Ag NPs were spherical and had an average diameter of 9.95 nm. The produced Ag NP-embedded WK/PVA composite nanofiber-deposited cotton fabric surface was characterized by FTIR and dynamic contact angle measurements, and the nanofiber morphologies were characterized by scanning electron microscopy. The average diameter of the nanofibers formed by 0.1% Ag NP-embedded WK/PVA solution was 146.7 nm. The antibacterial activity of the surface of cotton fabrics coated with electrospun composite nanofibers was evaluated against the two most common wound-causing pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. The cotton fabric coated with 0.1% Ag NP-embedded WK/PVA nanofibers showed very good antibacterial activity against both pathogens, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed good cytocompatibility against L-929 mouse fibroblast cells. However, the increase in Ag NP content in the nanofibers to 0.2% negatively affected the cell viability due to the high release rate of Ag ions. The results achieved show that the developed wound dressing has good potential for wound healing applications.

A disposable paper-based electrochemical biosensor decorated by electrospun cellulose acetate nanofibers for highly sensitive bio-detection.

Paper-based electrochemical sensors have the characteristics of flexibility, biocompatibility, environmental protection, low cost, wide availability, and hydropathy, which make them very suitable for the development and application of biological detection. This work proposes electrospun cellulose acetate nanofiber (CA NF)-decorated paper-based screen-printed (PBSP) electrode electrochemical sensors. The CA NFs were directly collected on the PBSP electrode through an electrospinning technique at an optimized voltage of 16 kV for 10 min. The sensor was functionalized with different bio-sensitive materials for detecting different targets, and its sensing capability was evaluated by CV, DPV, and chronoamperometry methods. The test results demonstrated that the CA NFs enhanced the detection sensitivity of the PBSP electrode, and the sensor showed good stability, repeatability, and specificity (p < 0.01, N = 3). The electrochemical sensing of the CA NF-decorated PBSP electrode exhibited a short detection duration of ∼5-7 min and detection ranges of 1 nmol mL-1-100 µmol mL-1, 100 fg mL-1-10 µg mL-1, and 1.5 × 102-106 CFU mL-1 and limits of detection of 0.71 nmol mL-1, 89.1 fg mL-1, and 30 CFU mL-1 for glucose, Ag85B protein, and E. coli O157:H7, respectively. These CA NF-decorated PBSP sensors can be used as a general electrochemical tool to detect, for example, organic substances, proteins, and bacteria, which are expected to achieve point-of-care testing of pathogenic microorganisms and have wide application prospects in biomedicine, clinical diagnosis, environmental monitoring, and food safety.

Sulfated hyaluronic acid/collagen-based biomimetic hybrid nanofiber skin for diabetic wound healing: Development and preliminary evaluation.

Diabetic foot ulcers (DFUs) are one of the most serious and devastating complication of diabetes, manifesting as foot ulcers and impaired wound healing in patients with diabetes mellitus. To solve this problem, sulfated hyaluronic acid (SHA)/collagen-based nanofibrous biomimetic skins was developed and used to promote the diabetic wound healing and skin remodeling. First, SHA was successfully synthetized using chemical sulfation and incorporated into collagen (COL) matrix for preparing the SHA/COL hybrid nanofiber skins. The polyurethane (PU) was added into those hybrid scaffolds to make up the insufficient mechanical properties of SHA/COL nanofibers, the morphology, surface properties and degradation rate of hybrid nanofibers, as well as cell responses upon the nanofibrous scaffolds were studied to evaluate their potential for skin reconstruction. The results demonstrated that the SHA/COL, SHA/HA/COL hybrid nanofiber skins were stimulatory of cell behaviors, including a high proliferation rate and maintaining normal phenotypes of specific cells. Notably, SHA/COL and SHA/HA/COL hybrid nanofibers exhibited a significantly accelerated wound healing and a high skin remodeling effect in diabetic mice compared with the control group. Overall, SHA/COL-based hybrid scaffolds are promising candidates as biomimetic hybrid nanofiber skin for accelerating diabetic wound healing.

Synthesis of biocomposites from microalgal peptide incorporated polycaprolactone/ κ- carrageenan nanofibers and their antibacterial and wound healing property.

Antimicrobial peptides (AMPs) are promising novel agents for targeting a wide range of pathogens. In this study, microalgal peptides derived from native microalgae were incorporated into polycaprolactone (PCL) with ƙ-Carrageenan (ƙ-C) forming nanofibers using the electrospinning method. The peptides incorporated in the nanofibers were characterized by fourier infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy (SEM), and contact angle measurement. The results showed that peptides with molecular weights < 10 kDa, when loaded into nanofibers, exhibited lower wettability. The SEM analysis revealed a thin, smooth, interconnected bead-like structures. The antimicrobial activity of the electrospun nanofibers was evaluated through disc diffusion, and minimum inhibitory activity against Escherichia coli (MTTC 443), and Staphylococcus aureus (MTTC 96), resulting in zones of inhibition of 24 ± 0.5 mm and 14 ± 0.5 mm, respectively. The in vitro biocompatibility of the synthesized nanofibers was confirmed using in HEK 293 cell lines with an increased cell viability. Interestingly, the fibers also exhibited a significant wound-healing properties when used in vitro scratch assays. In conclusion, algal peptides incorporated with PCL/ ƙ-C were found to exhibit antimicrobial and biocompatible biomaterials for wound healing applications.

Smart Electrospun Nanofibers from Short Peptidomimetics Based on Pyrrolo-pyrazole Scaffold.

We prepared a small library of short peptidomimetics based on 3-pyrrolo-pyrazole carboxylate, a non-coded γ-amino acid, and glycine or alanine. The robust and eco-friendly synthetic approach adopted allows to obtain the dipeptides in two steps from commercial starting materials. This gives the possibility to shape these materials by electrospinning into micro- and nanofibers, in amounts required to be useful for coating surfaces of biomedical relevance. To promote high quality of electrospun fibers, different substitution patterns were evaluated, all for pure peptide fibers, free of any polymer or additive. The best candidate, which affords a homogeneous fibrous matrix, was prepared in larger amounts, and its biocompatibility was verified. This successful work is the first step to develop a new biomaterial able to produce pristine peptide-based nanofibers to be used as helpful component or stand-alone scaffolds for tissue engineering or for the surface modification of medical devices.

Fabrication and In-Vivo Evaluation of Polyvinyl pyrrolidone/Poloxamer 188 Hybrid Nanofibers of Deflazacort.

The superior flexibility, efficient drug loading, high surface-to-volume ratio, ease of formulation, and cost-controlled production are considered exceptional advantages of nanofibers (NFs) as a smart delivery system. Deflazacort (DEF) is an anti-inflammatory and immunosuppressant agent. It is categorized as a poorly soluble class II drug. In this study, DEF-loaded polymeric nanofibrous using the electrospinning technique mats, Polyvinyl pyrrolidone (PVP) with or without Poloxamer 188 (PX) were used as mat-forming polymers. Microscopical imaging, drug content (%), and in vitro dissolution studies were conducted for all NFs formulae (F1-F7). All NFs improved the DEF dissolution compared to the unprocessed form, with the superiority of the PVP/PX hybrid. The optimized formula (F7) exhibited an average diameter of 655.46 ± 90.4 nm and % drug content of 84.33 ± 5.58. The dissolution parameters of DEF loaded in PVP/PX NFs (F7) reflected a release of 95.3 % ± 3.1 and 102.6 % ± 1.7 after 5 and 60 min, respectively. NFs (F7) was investigated for drug-polymer compatibility using Fourier-Transform Infrared Spectroscopy (FTIR), Powder X-ray diffraction analysis (PXRD), and Differential Scanning Calorimetry (DSC). In vivo anti-inflammatory study employing male Sprague-Dawley rats showed a significant reduction of rat paw edema for F7 (p < 0.05) compared with unprocessed DEF with a normal epidermal and dermal skin structure comparable to the healthy negative control. Immunohistochemical and morphometric data displayed similarities between the immune reaction of F7 and the negative healthy control. The finding of this work emphasized that DEF loaded in PVP/PX NFs could be considered a useful strategy for enhancing the therapeutic performance of DEF.

Electrospun multi-chamber core-shell nanofibers and their controlled release behaviors: A review.

Core-shell structure is a concentric circle structure found in nature. The rapid development of electrospinning technology provides more approaches for the production of core-shell nanofibers. The nanoscale effects and expansive specific surface area of core-shell nanofibers can facilitate the dissolution of drugs. By employing ingenious structural designs and judicious polymer selection, specialized nanofiber drug delivery systems can be prepared to achieve controlled drug release. The synergistic combination of core-shell structure and materials exhibits a strong strategy for enhancing the drug utilization efficiency and customizing the release profile of drugs. Consequently, multi-chamber core-shell nanofibers hold great promise for highly efficient disease treatment. However, little attention concentration is focused on the effect of multi-chamber core-shell nanofibers on controlled release of drugs. In this review, we introduced different fabrication techniques for multi-chamber core-shell nanostructures, including advanced electrospinning technologies and surface functionalization. Subsequently, we reviewed the different controlled drug release behaviors of multi-chamber core-shell nanofibers and their potential needs for disease treatment. The comprehensive elucidation of controlled release behaviors based on electrospun multi-chamber core-shell nanostructures could inspire the exploration of novel controlled delivery systems. Furthermore, once these fibers with customizable drug release profiles move toward industrial mass production, they will potentially promote the development of pharmacy and the treatment of various diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Oriented Graphene Oxide Scaffold Promotes Nerve Regeneration in vitro and in vivo.

Background: Treating peripheral nerve injuries (PNI) with defects remains challenging in clinical practice. The commercial conduits have shown suboptimal nerve regeneration and functional recovery due to their basic tubular design without electroactive and oriented topographical cues. Purpose: To develop a new scaffold with oriented microstructure and electroactive Graphene oxide (GO) and investigate its' therapeutic effect on nerve regeneration in vitro and in vivo. Methods: This study employed a straightforward approach to co-spin PCL and GO, yielding an oriented hybrid nanofibrous scaffold known as the O-GO/PCL scaffold. The physical and chemical properties of nanofibrous scaffold were tested by scanning electron microscopy (SEM), transmission electron microscope (TEM), tensile test and so on. Primary Schwann cells (SCs) and dorsal root ganglia (DRG) were used to investigate the impact of the newly developed scaffolds on the biological behavior of neural cells in vitro. Transcriptome sequencing (mRNA-seq) was employed to probe the underlying mechanisms of the synergistic effect of electroactive GO and longitudinal topographic guidance on nerve regeneration. Furthermore, the developed O-GO/PCL scaffold was utilized to bridge a 10-mm sciatic nerve defect in rat, aiming to investigate its therapeutic potential for peripheral nerve regeneration in vivo. Results and discussion: The SEM and TEM revealed that the newly developed O-GO/PCL scaffold showed longitudinally oriented microstructure and GO particles were homogenously and uniformly distributed inside the nanofibers. Primary SCs were utilized to assess the biocompatibility of the GO-based scaffold, revealing that negligible cytotoxicity when GO concentration does not exceed 0.5%. In vitro analysis of nerve regeneration demonstrated that axons in the O-GO/PCL group exhibited an average length of 1054.88 ± 161.32 µm, significant longer than those in the other groups (P < 0.05). Moreover, mRNA sequencing results suggested that the O-GO/PCL scaffold could enhance nerve regeneration by upregulating genes associated with neural regeneration, encompassing ion transport, axon guidance and cell-cell interactions. Most importantly, we employed the O-GO/PCL scaffold to repair a 10-mm sciatic nerve defect in rat, resulting in augmented nerve regeneration, myelination, and functional recovery. Conclusion: The O-GO/PCL scaffold with oriented microstructure and electroactive GO represents a promising heral nerve reconstruction.

Electrospun organic/inorganic hybrid nanofibers for accelerating wound healing: a review.

Electrospun nanofiber membranes hold great promise as scaffolds for tissue reconstruction, mirroring the natural extracellular matrix (ECM) in their structure. However, their limited bioactive functions have hindered their effectiveness in fostering wound healing. Inorganic nanoparticles possess commendable biocompatibility, which can expedite wound healing; nevertheless, deploying them in the particle form presents challenges associated with removal or collection. To capitalize on the strengths of both components, electrospun organic/inorganic hybrid nanofibers (HNFs) have emerged as a groundbreaking solution for accelerating wound healing and maintaining stability throughout the healing process. In this review, we provide an overview of recent advancements in the utilization of HNFs for wound treatment. The review begins by elucidating various fabrication methods for hybrid nanofibers, encompassing direct electrospinning, coaxial electrospinning, and electrospinning with subsequent loading. These techniques facilitate the construction of micro-nano structures and the controlled release of inorganic ions. Subsequently, we delve into the manifold applications of HNFs in promoting the wound regeneration process. These applications encompass hemostasis, antibacterial properties, anti-inflammatory effects, stimulation of cell proliferation, and facilitation of angiogenesis. Finally, we offer insights into the prospective trends in the utilization of hybrid nanofiber-based wound dressings, charting the path forward in this dynamic field of research.

Tuning Molecular Motion Enhances Intrinsic Fluorescence in Peptide Amphiphile Nanofibers.

Peptide amphiphiles (PAs) are highly tunable molecules that were recently found to exhibit aggregation-induced emission (AIE) when they self-assemble into nanofibers. Here, we leverage decades of molecular design and self-assembly study of PAs to strategically tune their molecular motion within nanofibers to enhance AIE, making them a highly useful platform for applications such as sensing, bioimaging, or materials property characterization. Since AIE increases when aggregated molecules are rigidly and closely packed, we altered the four most closely packed amino acids nearest to the hydrophobic core by varying the order and composition of glycine, alanine, and valine pairs. Of the six PA designs studied, C16VVAAK2 had the highest quantum yield at 0.17, which is a more than 10-fold increase from other PA designs including the very similar C16AAVVK2, highlighting the importance of precise amino acid placement to anchor rigidity closest to the core. We also altered temperature to increase AIE. C16VVAAK2 exhibited an additional 4-fold increase in maximum fluorescence intensity when the temperature was raised from 5 to 65 °C. As the temperature increased, the secondary structure transitioned from ß-sheet to random coil, indicating that further packing an already aligned molecular system makes it even more readily able to transfer energy between the electron-rich amides. This work both unveils a highly fluorescent AIE PA system design and sheds insights into the molecular orientation and packing design traits that can significantly enhance AIE in self-assembling systems.

Tuning Supramolecular Chirality in Iodinated Amphiphilic Peptides Through Tripeptide Linker Editing.

Protease-cleavable supramolecular oligopeptide nanofilaments are promising materials for targeted therapeutics and diagnostics. In these systems, single amino acid substitutions can have profound effects on the supramolecular structure and consequent proteolytic degradation, which are critical parameters for their intended applications. Herein, we describe changes to the self-assembly and proteolytic cleavage of iodine containing sequences for future translation into matrix metalloprotease (MMP-9)-activated supramolecular radio-imaging probes. We use a systematic single amino acid exchange in the tripeptide linker region of these peptide amphiphiles to provide insights into the role of each residue in the supramolecular assemblies. These modifications resulted in dramatic changes in the nature of the assembled structures formed, including an unexpected chiral inversion. By using circular dichroism, atomic force microscopy, Fourier transform infrared spectroscopy, and molecular dynamics simulations, we found that the GD loop, a common motif in ß-turn elements, induced a reversal of the chiral orientation of the assembled nanofibers. In addition to the impact on peptide packing and chirality, MMP-9-catalyzed hydrolysis was evaluated for the four peptides, with the ß-sheet content found to be a stronger determinant of enzymatic hydrolysis than supramolecular chirality. These observations provide fundamental insights into the sequence design in protease cleavable amphiphilic peptides with the potential for radio-labeling and selective biomedical applications.

Hydrophilic and hydrophobic drug release from core (polyvinylpyrrolidone)-sheath (ethyl cellulose) pressure-spun fibers.

A core-sheath structure is one of the methods developed to overcome the challenges often faced when using monolithic fibers for drug delivery. In this study, fibers based on polyvinylpyrrolidone (core) and ethyl cellulose (sheath) were successfully produced using a novel core-sheath pressure-spinning process. For comparison, these two polymers were also processed into as blend fibers. All samples were then investigated for their performances in releasing water-soluble ampicillin (AMP) and poorly water-soluble ibuprofen (IBU) model drugs. Scanning electron,digital and confocal microscopy confirmed that fibers with a core-sheath structure were successfully made. Fourier transform infrared spectroscopy showed the success of the pressure-spinning technique in encapsulating AMP/IBU in all fiber samples. Compared to blend fibers, the core-sheath fibers had better performance in encapsulating both water-soluble and poorly water-soluble drugs. Moreover, the core-sheath structure was able to reduce the initial burst release and provided a better sustained release profile than the blend fiber analog. In conclusion, the pressure-spinning method was capable of producing core-sheath and blend fibers that could be used for the loading of either hydrophilic or hydrophobic drugs for controlled drug delivery systems.