Nanofibrous Scaffolds Research Articles

Hybrid organosilane nanofibre scaffold formation supporting cell adhesion and growth

Hybrid organosilane nanofibre scaffold formation supporting cell adhesion and growth

Rapid cyclic stretching induces a synthetic, proinflammatory phenotype in cultured human intestinal smooth muscle, with the potential to alter signaling to adjacent bowel cells.

Bowel smooth muscle experiences mechanical stress constantly during normal function, and pathologic mechanical stressors in disease states. We tested the hypothesis that pathologic mechanical stress could alter transcription to induce smooth muscle phenotypic class switching. Primary human intestinal smooth muscle cells (HISMCs), seeded on electrospun aligned poly-ε-caprolactone nano-fibrous scaffolds, were subjected to pathologic, high frequency (1 Hz) uniaxial 3% cyclic stretch (loaded) or kept unloaded in culture for 6 hours. Total RNA sequencing, qRT-PCR, and quantitative immunohistochemistry defined loading-induced changes in gene expression. NicheNet predicted how differentially expressed genes might impact HISMCs and other bowel cells. Loading induced differential expression of 4537 genes in HISMCs. Loaded HISMCs had a less contractile phenotype, with increased expression of synthetic SMC genes, proinflammatory cytokines, and altered expression of axon guidance molecules, growth factors and morphogens. Many differentially expressed genes encode secreted ligands that could act cell-autonomously on smooth muscle and on other cells in the bowel wall. HISMCs demonstrate remarkably rapid phenotypic plasticity in response to mechanical stress that may convert contractile HISMCs into proliferative, fibroblast-like cells or proinflammatory cells. These mechanical stress-induced changes in HISMC gene expression may be relevant for human bowel disease.

Preparation of biocompatible Zein/Gelatin/Chitosan/PVA based nanofibers loaded with vitamin E-TPGS via dual-opposite electrospinning method

Wound management is a critical aspect of healthcare, necessitating effective and innovative wound dressing materials. Many existing wound dressings lack effectiveness and exhibit limitations, including poor antimicrobial activity, toxicity, inadequate moisture regulation, and weak mechanical performance. The aim of this study is to develop a natural-based nanofibrous structure that possesses desirable characteristics for use as a wound dressing. The chemical analysis confirmed the successful creation of Zein (Ze) (25% w/v) /gelatin (Gel) (10% w/v) /chitosan (CS) (2% w/v) /Polyvinyl alcohol (PVA) (10% w/v) nanofibrous scaffolds loaded with vitamin E tocopheryl polyethylene glycol succinate (Vit E). The swelling percentages of nanofiber (NF), NF + Vit E, cross-linked nanofiber (CNF), and CNF + Vit E were 49%, 110%, 410%, and 676%, respectively; and the degradation rates of NF, NF + Vit E, CNF, and CNF + Vit E were 29.57 ± 5.06%, 33.78 ± 7.8%, 14.03 ± 7.52%, 43 ± 6.27%, respectively. The antibacterial properties demonstrated that CNF impregnated with antibiotics reduced Escherichia coli (E. coli) counts by approximately 27–28% and Staphylococcus aureus (S. aureus) counts by about 34–35% compared to negative control. In conclusion, cross-linked Ze/Gel/CS/PVA nanofibrous scaffolds loaded with Vit E have potential as suitable wound dressing materials because environmentally friendly materials contribute to sustainable wound care and controlled degradation ensures wound dressings breakdown harmlessly.

Advances in Electrospun Poly(ε-caprolactone)-Based Nanofibrous Scaffolds for Tissue Engineering.

Tissue engineering has great potential for the restoration of damaged tissue due to injury or disease. During tissue development, scaffolds provide structural support for cell growth. To grow healthy tissue, the principal components of such scaffolds must be biocompatible and nontoxic. Poly(ε-caprolactone) (PCL) is a biopolymer that has been used as a key component of composite scaffolds for tissue engineering applications due to its mechanical strength and biodegradability. However, PCL alone can have low cell adherence and wettability. Blends of biomaterials can be incorporated to achieve synergistic scaffold properties for tissue engineering. Electrospun PCL-based scaffolds consist of single or blended-composition nanofibers and nanofibers with multi-layered internal architectures (i.e., core-shell nanofibers or multi-layered nanofibers). Nanofiber diameter, composition, and mechanical properties, biocompatibility, and drug-loading capacity are among the tunable properties of electrospun PCL-based scaffolds. Scaffold properties including wettability, mechanical strength, and biocompatibility have been further enhanced with scaffold layering, surface modification, and coating techniques. In this article, we review nanofibrous electrospun PCL-based scaffold fabrication and the applications of PCL-based scaffolds in tissue engineering as reported in the recent literature.

Electrospun "Hard-Soft" Interpenetrating Nanofibrous Tissue Scaffolds Facilitating Enhanced Mechanical Strength and Cell Proliferation.

"Soft" hydrogel-based macroporous scaffolds have been widely used in tissue engineering and drug delivery applications due to their hydrated interfaces and macroporous structures, but have drawbacks related to their weak mechanics and often weak adhesion to cells. In contrast, "hard" poly(caprolactone) (PCL) electrospun fibrous networks have desirable mechanical strength and ductility but offer minimal interfacial hydration and thus limited capacity for cell proliferation. Herein, we demonstrate the fabrication of interpenetrating nanofibrous networks based on coelectrospun PCL and poly(oligoethylene glycol methacrylate) (POEGMA) nanofibers that exhibit the mechanical benefits of PCL but the interfacial hydration benefits of hydrogels. The electrospinning process results in partially aligned but interpenetrating fiber network with minimal internal phase separation, leading to anisotropic but strong mechanical properties even in the hydrated state; apparent ultimate tensile strengths of the swollen scaffolds ranged from 429 ± 39 kPa in the direction of fiber alignment (longitudinal) to 86 ± 25 kPa perpendicular to fiber alignment (cross-longitudinal), typical of PCL-based scaffolds and enabling efficient suture retention in different directions. However, contact angle measurements indicate hydrogel-like interfacial properties due to the presence of the interpenetrating POEGMA network. C2C12 myoblast proliferation in the PCL-POEGMA scaffolds was 50% higher than that observed on PCL-only scaffolds, a result attributed to the presence of the more hydrophilic POEGMA interpenetrating nanofiber network. Overall, this method is demonstrated to represent a facile single-step strategy to fabricate strong macroporous but still interfacially hydrophilic scaffolds for tissue engineering applications.

Electrospun zeolitic imidazole framework-8 loaded silk fibroin/polycaprolactone nanofibrous scaffolds for biomedical application

The development of electrospun nanofibrous scaffolds (NFSs) have aroused much attraction in the field of biomedical engineering, due to their small fiber diameter, high specific surface area, and excellent extracellular matrix comparability. The main focus of this study is to design and fabricate novel zeolitic imidazole framework-8 (ZIF-8)-loaded silk fibrin/polycaprolactone (SF/PCL) nanofiber composite scaffolds by using the electrospinning strategy. Firstly, ZIF-8 was synthesized and characterized, which showed remarkable features in terms of shape, size, chemical and physical properties. Then, three different amounts of ZIF-8 were encapsulated into SF/PCL nanofibers during electrospinning, to investigate how the addition of ZIF-8 affected the morphology, and structure, as well as physical, mechanical, and biological properties of the nanofiber composite scaffolds. It was found that the addition of ZIF-8 didn't change the nanofibrous morphology of the composite scaffold, and no bead-like structure were found for the SF/PCL composite scaffolds loading with or without ZIF-8. The appropriate addition of ZIF-8 could significantly increase the mechanical properties of SF/PCL NFSs. The SF/PCL NFS containing 5% ZIF-8 showed high ultimate stress and initial modulus, which were 40.31 ± 2.31 MPa, and 569.19 ± 21.38 MPa, respectively. Furthermore, the MTT assay indicated that the pure SF/PCL scaffold and one with 1% ZIF-8 exhibited nearly identical cell compatibility toward human dermal fibroblast (HDF) cells, but some obvious cytotoxicity was observed with the increase of ZIF-8 content. However, the incorporation of ZIF-8 into SF/PCL NFSs was found to have excellent antibacterial rate against both E. coli and S. aureus. In all, the incorporation of 1% ZIF-8 could impart the SF/PCL NFS with balanced bio-function, making it a promising candidate for diverse biomedical applications such as tissue engineering and wound healing.

Hierarchically structured nanofibrous scaffolds spatiotemporally mediate the osteoimmune micro-environment and promote osteogenesis for periodontitis-related alveolar bone regeneration

Periodontitis suffer from inflammation-induced destruction of periodontal tissues, resulting in the serious loss of alveolar bone. Controlling inflammation and promoting bone regeneration are two crucial aspects for periodontitis-related alveolar bone defect treatment. Herein, we developed a hierarchically structured nanofibrous scaffold with a nano-embossed sheath and a bone morphogenetic protein 2-loaded core to match the periodontitis-specific features that spatiotemporally modulated the osteoimmune environment and promoted periodontal bone regeneration. We investigated the potential of this unique scaffold to treat periodontitis-related alveolar bone defects in vivo and in vitro. The results demonstrated that the hierarchically structured scaffold effectively reduced the inflammatory levels in macrophages and enhanced the osteogenic potential of bone mesenchymal stem cells in an inflammatory microenvironment. Moreover, in vivo experiments revealed that the hierarchically structured scaffold significantly ameliorated inflammation in the periodontium and inhibited alveolar bone resorption. Notably, the hierarchically structured scaffold also exhibited a prolonged effect on promoting alveolar bone regeneration. These findings highlight the significant therapeutic potential of hierarchically structured nanofibrous scaffolds for the treatment of periodontitis, and their promising role in the field of periodontal tissue regeneration. Statement of Significance: We present a novel hierarchically structured nanofibrous scaffold of coupling topological and biomolecular signals for precise spatiotemporal modulation of the osteoimmune micro-environment. Specifically, the scaffold was engineered via coaxial electrospinning of the poly(ε-caprolactone) sheath and a BMP-2/polyvinyl alcohol core, followed by surface-directed epitaxial crystallization to generate cyclic nano-lamellar embossment on the sheath. With this unique hierarchical structure, the cyclic nano-lamellar sheath provided a direct nano-topographical cue to alleviate the osteoimmune environment, and the stepwise release of BMP-2 from the core provided a biological cue for bone regeneration. This research underscores the potential of hierarchically structured nanofibrous scaffolds as a promising therapeutic approach for periodontal tissue regeneration and highlights their role in advancing periodontal tissue engineering.

Mesenchymal stem cells derived extracellular vesicles modified PLGA electrospinning nanofibrous scaffolds for corneal and retinal repair

Tissue self-renewal is crucial for ocular diseases such as corneal damage and retinal holes. In this study, a novel Poly (lactic-co-glycolic acid) (PLGA) electrospinning nanofibrous scaffold (PLGAENS), loaded with mesenchymal stem cells-derived extracellular vesicles (MSC-EVs), was developed to accelerate the healing of the cornea and retina. In-vitro experiments confirmed the supportive properties of PLGAENS, demonstrating its ability to promote cellular proliferation, migration, and extension. In the rat corneal alkali burn model and rabbit retinal hole model, MSC-EVs modified PLGAENS (PLGAMSC-EVs) accelerated the restoration of the corneal epithelium and stroma, as well as the closure of retinal holes. Additionally, miR-21-5p was identified as being enriched in MSC-EVs. Mechanistically, miR-21-5p suppressed scar formation by targeting the programmed cell death protein 4 (PDCD4) gene, reducing fibrosis and the expression of collagen-related genes, which helped maintain corneal transparency and retinal integrity. Overall, these findings underscored the potential of PLGAMSC-EVs in promoting ocular wound healing and suggested a promising new therapeutic strategy for the clinical treatment of corneal damage and retinal holes.

Evaluating the efficacy of uniformly designed square mesh resin 3D printed scaffolds in directing the orientation of electrospun PCL nanofibers

Replicating the architecture of extracellular matrices (ECM) is crucial in tissue engineering to support tissues’ natural structure and functionality. The ECM’s structure plays a significant role in directing cell alignment. Electrospinning is an effective technique for fabricating nanofibrous substrates that mimic the architecture of extracellular matrices (ECM). This study aims to evaluate the efficacy of resin 3D-printed scaffolds made from a low-conductivity material (i.e., a resin composed of methacrylated oligomers, monomers, and photoinitiators) in directing the alignment of electrospun polycaprolactone (PCL) nanofibers. Six 3D-printed scaffolds were fabricated using stereolithography (SLA) technology and strategically positioned on an aluminum foil collector plate during electrospinning. The structured geometry of the scaffolds, rather than the local electric field distribution, is hypothesized to guide nanofiber alignment. Images acquired through the scanning electron microscopy (SEM) were used to analyze and statistically quantify the nanofibrous scaffolds to evaluate the alignment of nanofibers over the scaffolds compared to a set of randomly deposited control nanofiber samples in the absence of the 3D printed scaffolds. SEM images also showed significant alignment of nanofibers within the pores of scaffolds, using histograms as a means for indicating the distribution of orientation angles. Statistical analysis revealed that this distribution deviates from normality due to the deviations in the tails and the existence of relatively smaller peaks at angles relative to 0°, particularly within a range of ± 50° and ± 40°. It is further found that the average peak orientation angle relative to 0° had a maximum probability of 0.014. Furthermore, the statistical analysis confirmed the distribution and significant differences in orientation between test samples with 3D-printed scaffolds and control samples. These findings demonstrate the effectiveness of resin 3D-printed scaffolds, particularly their geometric filtering effect, leading to controlled nanofiber alignment, which is proposed to be beneficial for enhancing cell adhesion, proliferation, and cell migration in tissue engineering applications.

Cell migration within porous electrospun nanofibrous scaffolds in a mouse subcuticular implantation model.

Cellular infiltration into electrospun nanofibers (NFs) is limited due to the dense structure and small pore sizes. We developed a programmed NF collector that can fabricate porous NFs with desired pore sizes and thickness. Previously we demonstrated improved cellular proliferation and differentiation of osteoblasts, osteoclasts, and fibroblasts with increased pore sizes of polycaprolactone (PCL) NF in-vitro. This study investigated in-vivo host cell migration and vascular ingrowth within porous NF sheets implanted subcutaneously in a mouse model. Two types of PCL NFs with well-defined pore sizes were created using varying speeds of the NF collector: NF-zero (no movement, pore size 14.4 ± 8.9 µm2) and NF-high (0.232 mm/min, pore size 286.7 ± 381.9 µm2). The NF obtained by using classical flat NF collector (2D NF, pore size 1.09 ± 1.7 µm2) was a control. The three formulae of NFs were implanted subcutaneously in 18 BALB/cJ mice. Animals were killed 7 and 28-days after implantation (n = 3 per group per time point). The tissue with implanted NFs were collected for histologic analysis. Overall, 7-day samples showed little inflammatory response. At 28-days, the degree of tissue penetration of PCL NF sheet matrices was linked to pore size and area. NFs with the largest pore area had more efficient tissue migration and new blood vessel formation compared to those with smaller pore sizes. No newly formed blood vessels were observed in the 2D NF group. A porous NF scaffold with controllable pore size has potential for tissue repair/regeneration in situ with potential for many applications in orthopaedics.

Bioactive stem cell-laden 3D nanofibrous scaffolds for tissue engineering

This study presents biomimetic nanoscaffolds composed of electrospun polycaprolactone-collagen (PCL-Coll) nanofibers, loaded with bioactive Arnebia euchroma (AE) extract and stem cells, to develop cell-based tissue engineering constructs. The incorporation of AE extract, known for its antioxidant and anti-inflammatory properties, into the PCL-Coll nanofibers resulted in nanoscaffolds denoted as PCL-Coll/AE0, PCL-Coll/AE5, PCL-Coll/AE10, and PCL-Coll/AE15, corresponding to AE extract concentrations of 0.0, 5.0, 10.0, and 15.0 wt%, respectively. The PCL-Coll/AE nanoscaffolds exhibited high porosity values of 62.81 ± 4.78 %, 59.9 ± 2.10 %, 52.44 ± 2.66 %, and 46.32 ± 1.35 %, respectively, thereby providing an optimal 3D environment for cell attachment and proliferation. Analysis of the AE extract revealed the presence of abundant shikonin, a key bioactive compound, as indicated by its characteristic absorption bands at 490, 520, and 560 nm. FE-SEM data confirmed the homogeneous immobilization of AE compounds within the 3D nanofiber scaffolds, with fibers averaging 316 ± 137 nm in diameter, falling within the range of natural collagen fibers. To evaluate the structural integrity of the fully stem cell-laden scaffolds, we assessed cell growth, cell attachment within the PCL-Coll/AE nanoscaffolds, the cytoprotective effects of AE extract, and the expression levels of stemness-related genes, including Nanog, Rex1, Sox2, Oct4, Klf4, and C-Myc. Real-time PCR assays indicated that key indicators of stemness were upregulated, with average increases from 120 ± 15 % in PCL-Coll/AE0 to 250 ± 30 % in PCL-Coll/AE15 over a two-week period. These upregulations promote cell proliferation and facilitate cell cycle progression. Data indicate that increasing the concentration of bioactive AE extract within the scaffolds enhanced cell adhesion on the scaffold surface and improved cell viability after 7 days of culture, with viability rising from 109 ± 6.15 % in PCL-Coll/AE0 to 145.5 ± 10.11 % in PCL-Coll/AE15. Cytoprotective assays against oxidative stress induced by H₂O₂ revealed relative cell viability for PCL-Coll/AE0, PCL-Coll/AE5, PCL-Coll/AE10, and PCL-Coll/AE15 as 42.78 ± 5.85 %, 49.29 ± 6.79 %, 64.98 ± 3.32 %, and 78.68 ± 3.09 %, respectively. These results correlate with the antioxidant potency of AE extract compounds, particularly shikonin and its derivatives. Therefore, the cell-laden biomimetic PCL-Coll/AE15 scaffolds, which demonstrate sustained stemness features and a continuous local release of bioactive AE compounds, represent a promising candidate for tissue engineering applications.

Lysine-Mediated Yttrium Oxide Nanoparticle-Incorporated Nanofibrous Scaffolds with Tunable Cell Adhesion, Proliferation, and Antimicrobial Potency for In Vitro Wound-Healing Applications.

The intricate healing mechanism of chronic wounds and their multitude of healing-related obstacles, such as infections, compromised cellular processes, and impediments to the healing process, pose a significant healthcare problem. Exploration of metal oxide nanoparticles, such as yttrium oxide (Y2O3) nanoparticles, can lead to innovative discoveries in the field of chronic wound healing by offering cues that promote cell proliferation in the scaffolds. To achieve this, Y2O3 nanoparticles were synthesized and incorporated within poly(vinyl alcohol) (PVA) nanofibrous scaffolds. Moreover, lysine was infused in the nanofibrous scaffolds to tune its cell adhesion and antimicrobial property. The structure and morphology of the synthesized nanofibers were confirmed through various physicochemical characterizations. Notably, all the fabricated scaffolds have remarkably tuned WVTR values within the range of 2000-2500 g/m2/day, favorable for removing the wound exudate, which facilitate the healing process. The scaffolds exhibited substantial antimicrobial property of approximately 68% and 72.2% against both E. coli and S. aureus at optimized Y2O3 loading. They further prevented the formation of biofilm by 68.6% for S. aureus and 51.2% for P. aeruginosa, suggesting the inhibition of recurrent wound infection. The scaffolds illustrated good blood biocompatibility, cytocompatibility, and cell adhesion capabilities. In vitro ROS inhibition study also corroborated the antioxidant property of the scaffold. Similarly, the wound scratching experiment showed high proliferative capability of a yttria-loaded PVA/lysine (S3) sample through the development of an extracellular matrix support. Molecular insight of wound healing was also validated through flow cytometry analysis and immunocytochemistry imaging studies. The findings revealed increased collagen I (Col-I) expression of approximately 19.48% in cultured fibrocytes. The findings are validated from immunocytochemistry imaging. In summary, the results furnish a captivating paradigm for the use of these scaffolds as a therapeutic biomaterial and to foster their potential efficacy toward wound care management.

Cotton wool-like ion-doped bioactive glass nanofibers: investigation of Zn and Cu combined effect

Electrospinning is a versatile and straightforward technique to produce nanofibrous mats with different morphologies. In addition, by optimizing the solution, processing, and environmental parameters, three-dimensional (3D) nanofibrous scaffolds can also be created using this method. In this work, the preparation and characterization of bioactive glass (BG) scaffolds based on the SiO2-CaO sol-gel system, a biomaterial with a highly reactive surface, is reported. The electrospinning technique was combined with sol-gel methods to obtain nanofibrous 3D cotton wool-like scaffolds. The addition of zinc and copper ions to the silica-calcia system was examined, and the influence of these ions on the material properties and characteristics was investigated by various characterization techniques, from morphological and chemical properties to antibacterial and wound closure capability, cell viability and ion release. Our findings show that the cotton wool-like ion-doped nanofibers are promising for wound healing applications.

An Insight into Biodegradable Polymers and their Biomedical Applications for Wound Healing.

Biodegradable polymers, encompassing both natural and synthetic polymers, have demonstrated efficacy as carriers for synthetic drugs, natural bioactive molecules, and inorganic metals. This is due to their ability to control the release of these substances. As a result, various advanced materials, such as nanoparticle- loaded hydrogels, nanofibrous scaffolds, and nanocomposites, have been developed. These materials have shown promise in enhancing processes, such as cell proliferation, vascular angiogenesis, hair growth, and wound healing management. Natural polymers, including hyaluronic acid, collagen, chitosan, gelatin, and alginate, as well as synthetic polymers like polylactic acid, polyglycolic acid, polylactic co-glycolic acid, and PCA, have significant potential for promoting wound healing. This study examines the advancements in biodegradable polymers for wound healing, specifically focusing on each polymer and its distinctive formulations. It also discusses the in vitro experiments conducted using different cell lines, as well as the in vivo studies that explore the numerous uses of these polymers in wound healing. The discussion also included the exploration of modifications or combinations of several polymers, as well as surface changes, in order to produce synergistic effects and address the limitations of individual polymers. The goal was to expedite the healing process of different chronic wounds. Due to this, there have been notable advancements in the technological use of polymeric mixes, including biodegradable polymer-based scaffolds, which have accelerated the process of wound healing.

Enhanced wound healing properties of biodegradable PCL/alginate core-shell nanofibers containing Salvia abrotanoides essential oil and ZnO nanoparticles

Electrospun nanofibrous membranes, with their unique structural features, can potentially enhance wound healing through controlled delivery of active agents. Here, an innovative porous nanofibrous membrane was developed as a dressing patch with antibacterial and anti-inflammatory functionalities for cutaneous wound healing. Zinc oxide nanoparticles (ZnO NPs) and Salvia abrotanoides essential oil (SAEO) were incorporated into sodium alginate, which served as the shell. Poly(ε-caprolactone) was used as the core of coaxial electrospun wound dressing nanofibers (PCL/SA@ZnO/SAEO). With the addition of ZnO NPs and SAEO, the average diameter of nanofibers was 187 ± 51 nm, with improved tensile strength (4.7 ± 0.4 MPa), elongation at break (32.9 ± 2.1), and elastic modulus (21.4 ± 2.0). Concurrent application of ZnO NPs and SAEO increased antimicrobial activity against Staphylococcus aureus and Escherichia coli and promoted the proliferation, attachment, and viability (>90 %) of L929 cells. The PCL/SA@ZnO/SAEO scaffold accelerated the healing time with total wound healing over 14 days in mouse models carrying full-thickness wounds compared to the nanofibrous scaffold without additives. Histopathological examinations demonstrated better tissue regeneration, i.e., enhanced collagen deposition, improved re-epithelialization, and neovascularization, and increased quantity of hair follicles. Moreover, the chicken chorioallantoic membrane assay confirmed the synergistic angiogenic effects of SAEO and ZnO NPs. Finally, the in vitro and in vivo results proposed the bioactive core-shell nanofibers synthesized as encouraging wound dressing materials for hastening the healing of cutaneous wounds.

Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds

Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds

Indomethacin Delivery from PCL Nanofibrous Scaffolds Enhances Biomineralization and Cell Adhesion: Biocompatible Scaffold Model for Teeth Regeneration

Indomethacin Delivery from PCL Nanofibrous Scaffolds Enhances Biomineralization and Cell Adhesion: Biocompatible Scaffold Model for Teeth Regeneration

Rhamnus prinoides leaf extract loaded polycaprolactone-cellulose acetate nanofibrous scaffold as potential wound dressing: An in vitro study

Rhamnus prinoides leaf contains carbohydrates, saccharides, phenolic acids, and diterpenes with antibacterial, wound-healing, and anti-inflammatory properties. In this study, Rhamnus prinoides leaf extract was successfully incorporated into polycaprolactone-cellulose acetate (PCL-CA) nanofibers through electrospinning technique for the first time. The mats' morphology, diameter, chemical, and crystalline structure were characterized. The study investigated the mats' antibacterial activity, wound healing, cytotoxicity, drug release behaviour, hydrophilicity, and water absorbency properties. The results revealed that the mats exhibited continuous, smooth, without-beads, and interconnected structures, with average fiber diameters ranging from 385 ± 21 nm to 332 ± 74 nm. The antibacterial effeciency was remarkable against S. aureus and E. coli, achieving bacterial reduction percentages exceeding 99 % at concentrations of 3 % and above against S. aureus and 5 % and above against E. coli. Cytotoxic tests showed low-cytotoxicity up to an extract concentration of 7 %. The extract release increases with an increase in concentration. In vitro wound healing assay, the mats enhanced cell migration to the wound area. Additionally, the incorporation of Rhamnus prinoides significantly improved the hydrophilicity and water absorbency of the nanofibers. Overall, the study highlights the mats' broad antimicrobial and wound healing properties with less cytotoxicity, hydrophilicity, and water absorbency, making them promising for use as wound dressings.

Stimulative piezoelectric nanofibrous scaffolds for enhanced small extracellular vesicle production in 3D cultures.

Small extracellular vesicles (sEVs) have great promise as effective carriers for drug delivery. However, the challenges associated with the efficient production of sEVs hinder their clinical applications. Herein, we report a stimulative 3D culture platform for enhanced sEV production. The proposed platform consists of a piezoelectric nanofibrous scaffold (PES) coupled with acoustic stimulation to enhance sEV production of cells in a 3D biomimetic microenvironment. Combining cell stimulation with a 3D culture platform in this stimulative PES enables a 15.7-fold increase in the production rate per cell with minimal deviations in particle size and protein composition compared with standard 2D cultures. We find that the enhanced sEV production is attributable to the activation and upregulation of crucial sEV production steps through the synergistic effect of stimulation and the 3D microenvironment. Moreover, changes in cell morphology lead to cytoskeleton redistribution through cell-matrix interactions in the 3D cultures. This in turn facilitates intracellular EV trafficking, which impacts the production rate. Overall, our work provides a promising 3D cell culture platform based on piezoelectric biomaterials for enhanced sEV production. This platform is expected to accelerate the potential use of sEVs for drug delivery and broad biomedical applications.

Graphene Oxide‐Incorporated Polylactic Acid/Polyamidoamine Dendrimer Electroconductive Nanocomposite as a Promising Scaffold for Guided Tissue Regeneration

AbstractIn the recent years, electroconductive scaffolds have shown promising capabilities in guided regeneration of electroactive tissues including nerve, heart muscle, bone, cartilage, and skin. Herein, the fabrication of a novel electroconductive poly (L‐lactic acid) (PLLA)/polyamidoamine (PAMAM) dendrimer nanofibrous scaffold containing graphene oxide (GO) nanosheets is described. The presence of PAMAM with amine terminal groups successfully aminolyzed PLLA. Interestingly, both PAMAM (5% w/w) and GO (0.5, 1, 2% w/w) not only contributed to reducing the fiber diameter, increasing the hydrophilicity and degradation rate, but also provided a nanocomposite scaffold with enhancement in electrical conductivity. By incorporating 1% w/w of GO, the nanocomposite scaffold exhibited optimized properties, including electrical conductivity (≈3.09 × 10−5 S m−1), crystallinity (≈ 47%), Young's modulus (≈16.95 MPa), as well as strength (≈1.58 MPa). This nanocomposite also demonstrated significant antibacterial activity of ≥ 90% against both gram‐positive and gram‐negative bacteria. Cellular assays confirmed acceptable cytocompatibility of the nanocomposite scaffolds containing GO and PAMAM, which can support the viability and proliferation of PC‐12 cells. In conclusion, the presence of GO nanosheets alongside PAMAM dendrimers can synergically promote the properties of the prepared nanofibrous mats which can be used as potential electroconductive scaffolds for guided tissue regeneration.