Electrospun polyvinyl alcohol nanofiber scaffolds incorporated strontium-substituted hydroxyapatite from sand lobster shells: synthesis, characterization, and in vitro biological properties.

The paper describes the synthesis of hydroxyapatite (HAp) and strontium-substituted hydroxyapatite (SrHAp) from sand lobster shells by a hydrothermal method. The HAp and SrHAp were incorporated into the polyvinyl alcohol (PVA) nanofiber scaffold through the eletrospinning method. The scaffolds were incorporated with 5wt% of hydroxyapatite (HAp), 5wt%, 10wt%, and 15% of SrHAp. The physicochemical, mechanical, and in vitro biological properties of the scaffold were evaluated. The incorporation of HAp or SrHAp was evidenced by the diffraction patterns and the phosphate functional groups related to HAp. The morphological results showed the decrement of fiber diameter in line with the increased SrHAp concentration. A tensile test was conducted to investigate the mechanical properties of the scaffolds, and the results showed that the scaffolds perform poorly at a higher SrHAp concentration because of exceeding agglomeration levels. The PVA/SrHAp15 performed the best antibacterial activity against E. coli and S. aureus with an inhibition zone of (15.2 ± 0.2) and (14.5 ± 0.8), respectively. The apatite formation was more abundant in PVA/SrHAp10 after immersion in a simulated body fluid (SBF). Cell viability results showed that the scaffold enabled the osteoblast cells to grow and proliferate. The biocompatibility of HAp and SrHAp resulted in the enhancement of cell adhesion. Based on all tests, the PVA/SrHAp 10 scaffold shows a strong candidate for further in vivo studies.

Orthogonally woven 3D nanofiber scaffolds promote rapid soft tissue regeneration by enhancing bidirectional cell migration.

Repairing large-area soft tissue defects caused by traumas is a major surgical challenge. Developing multifunctional scaffolds with suitable scalability and favorable cellular response is crucial for soft tissue regeneration. In this study, we developed an orthogonally woven three-dimensional (3D) nanofiber scaffold combining electrospinning, weaving, and modified gas-foaming technology. The developed orthogonally woven 3D nanofiber scaffold had a modular design and controlled fiber alignment. In vitro, the orthogonally woven 3D nanofiber scaffold exhibited adjustable mechanical properties, good cell compatibility, and easy drug loading. In vivo, for one thing, the implantation of an orthogonally woven 3D nanofiber scaffold in a full abdominal wall defect model demonstrated that extensive granulation tissue formation with enough mechanical strength could promote recovery of abdominal wall defects while reducing intestinal adhesion. Another result of diabetic wound repair experiments suggested that orthogonally woven 3D nanofiber scaffolds had a higher wound healing ratio, granulation tissue formation, collagen deposition, and re-epithelialization. Taken together, this novel orthogonally woven 3D nanofiber scaffold may provide a promising and effective approach for optimal soft tissue regeneration.

Hierarchically Assembled Nanofiber Scaffolds with Dual Growth Factor Gradients Promote Skin Wound Healing Through Rapid Cell Recruitment.

To address current challenges in effectively treating large skin defects caused by trauma in clinical medicine, the fabrication, and evaluation of a novel radially aligned nanofiber scaffold (RAS) with dual growth factor gradients is presented. These aligned nanofibers and the scaffold's spatial design provide many all-around "highways" for cell migration from the edge of the wound to the center area. Besides, the chemotaxis induced by two growth factor gradients further promotes cell migration. Incorporating epidermal growth factor (EGF) aids in the proliferation and differentiation of basal layer cells in the epidermis, augmenting the scaffold's ability to promote epidermal regeneration. Concurrently, the scaffold-bound vascular endothelial growth factor (VEGF) recruits vascular endothelial cells at the wound's center, resulting in angiogenesis and improving blood supply and nutrient delivery, which is critical for granulation tissue regeneration. The RAS+EGF+VEGF group demonstrates superior performance in wound immune regulation, wound closure, hair follicle regeneration, and ECM deposition and remodeling compared to other groups. This study highlights the promising potential of hierarchically assembled nanofiber scaffolds with dual growth factor gradients for wound repair and tissue regeneration applications.

Hierarchically Assembled Nanofiber Scaffold Guides Long Bone Regeneration by Promoting Osteogenic/Chondrogenic Differentiation of Endogenous Mesenchymal Stem Cells.

Critical-sized segmental long bone defects represent a challenging clinical dilemma in the management of battlefield and trauma-related injuries. The residual bone marrow cavity of damaged long bones contains many bone marrow mesenchymal stem cells (BMSCs), which provide a substantial source of cells for bone repair. Thus, a three-dimensional (3D) vertically aligned nanofiber scaffold (VAS) is developed with long channels and large pore size. The pore of VAS toward the bone marrow cavity after transplantation, enables the scaffolds to recruit BMSCs from the bone marrow cavity to the defect area. In vivo, it is found that VAS can significantly shorten gap distance and promote new bone formation compared to the control and collagen groups after 4 and 8 weeks of implantation. The single-cell sequencing results discovered that the 3D nanotopography of VAS can promote BMSCs differentiation to chondrocytes and osteoblasts, and up-regulate related gene expression, resulting in enhancing the activities of bone regeneration, endochondral ossification, bone trabecula formation, bone mineralization, maturation, and remodeling. The Alcian blue and bone morphogenetic protein 2 (BMP-2) immunohistochemical staining verified significant cartilage formation and bone formation in the VAS group, corresponding to the single-cell sequencing results. The study can inspire the design of next-generation scaffolds for effective long-bone regeneration is expected by the authors.

Enhancing Composite Toughness Through Hierarchical Interphase Formation.

High strength and ductility are highly desired in fiber-reinforced composites, yet achieving both simultaneously remains elusive. A hierarchical architecture is developed utilizing high aspect ratio chemically transformable thermoplastic nanofibers that form covalent bonding with the matrix to toughen the fiber-matrix interphase. The nanoscale fibers are electrospun on the micrometer-scale reinforcing carbon fiber, creating a physically intertwined, randomly oriented scaffold. Unlike conventional covalent bonding of matrix molecules with reinforcing fibers, here, the nanofiber scaffold is utilized - interacting non-covalently with core fiber but bridging covalently with polymer matrix - to create a high volume fraction of immobilized matrix or interphase around core reinforcing elements. This mechanism enables efficient fiber-matrix stress transfer and enhances composite toughness. Molecular dynamics simulation reveals enhancement of the fiber-matrix adhesion facilitated by nanofiber-aided hierarchical bonding with the matrix. The elastic modulus contours of interphase regions obtained from atomic force microscopy clearly indicate the formation of stiffer interphase. These nanoengineered composites exhibit a ≈60% and ≈100% improved in-plane shear strength and toughness, respectively. This approach opens a new avenue for manufacturing toughened high-performance composites.

Flexible Accelerated-Wound-Healing Antibacterial Hydrogel-Nanofiber Scaffold for Intelligent Wearable Health Monitoring.

Flexible epidermal sensors hold significant potential in personalized healthcare and multifunctional electronic skins. Nonetheless, achieving both robust sensing performance and efficient antibacterial protection, especially in medical paradigms involving electrophysiological signals for wound healing and intelligent health monitoring, remains a substantial challenge. Herein, we introduce a novel flexible accelerated-wound-healing biomaterial based on a hydrogel-nanofiber scaffold (HNFS) via electrostatic spinning and gel cross-linking. We effectively engineer a multifunctional tissue nanoengineered skin scaffold for wound treatment and health monitoring. Key features of HNFS include high tensile strength (24.06 MPa) and elasticity (214.67%), flexibility, biodegradability, and antibacterial properties, enabling assembly into versatile sensors for monitoring human motion and electrophysiological signals. Moreover, in vitro and in vivo experiments demonstrate that HNFS significantly enhances cell proliferation and skin wound healing, provide a comprehensive therapeutic strategy for smart sensing and tissue repair, and guide the development of high-performance "wound healing-health monitoring" bioelectronic skin scaffolds. Therefore, this study provides insights into crafting flexible and repairable skin sensors, holding potential for multifunctional health diagnostics and intelligent medical applications in intelligent wearable health monitoring and next-generation artificial skin fields.

Metal-Chelating Self-Assembling Peptide Nanofiber Scaffolds for Modulation of Neuronal Cell Behavior.

Synthetic peptides are promising structural and functional components of bioactive and tissue-engineering scaffolds. Here, we demonstrate the design of self-assembling nanofiber scaffolds based on peptide amphiphile (PA) molecules containing multi-functional histidine residues with trace metal (TM) coordination ability. The self-assembly of PAs and characteristics of PA nanofiber scaffolds along with their interaction with Zn, Cu, and Mn essential microelements were studied. The effects of TM-activated PA scaffolds on mammalian cell behavior, reactive oxygen species (ROS), and glutathione levels were shown. The study reveals the ability of these scaffolds to modulate adhesion, proliferation, and morphological differentiation of neuronal PC-12 cells, suggesting a particular role of Mn(II) in cell-matrix interaction and neuritogenesis. The results provide a proof-of-concept for the development of histidine-functionalized peptide nanofiber scaffolds activated with ROS- and cell-modulating TMs to induce regenerative responses.

Tideglusib-incorporated nanofibrous scaffolds potently induce odontogenic differentiation.

Pulp-Dentin regeneration is a key aspect of maintain tooth vitality and enabling good oral-systemic health. This study aimed to investigate a nanofibrous scaffold loaded with a small molecule i.e. Tideglusib to promote odontogenic differentiation. Tideglusib (GSK-3ß inhibitor) interaction with GSK-3ß was determined using molecular docking and stabilization of ß-catenin was examined by confocal microscopy. 3D nanofibrous scaffolds were fabricated through electrospinning and their physicochemical characterizations were performed. Scaffolds were seeded with mesenchymal stem cells or pre-odontoblast cells to determine the cells proliferation and odontogenic differentiation. Our results showed that Tideglusib (TG) binds with GSK-3ß at Cys199 residue. Stabilization and nuclear translocation of ß-catenin was increased in the odontoblast cells treated with TG. SEM analysis revealed that nanofibers exhibited controlled architectural features that effectively mimicked the natural ECM. UV-Vis spectroscopy demonstrated that TG was incorporated successfully and released in a controlled manner. Both kinds of biomimetic nanofibrous matrices (PCLF-TG100, PCLF-TG1000) significantly stimulated cells proliferation. Furthermore, these scaffolds significantly induced dentinogenic markers (ALP, and DSPP) expression and biomineralization. In contrast to current pulp capping material driving dentin repair, the sophisticated, polymeric scaffold systems with soluble and insoluble spatiotemporal cues described here can direct stem cell differentiation and dentin regeneration. Hence, bioactive small molecule-incorporated nanofibrous scaffold suggests an innovative clinical tool for dentin tissue engineering.

Nanofiber Scaffolds as Drug Delivery Systems Promoting Wound Healing.

Nanofiber scaffolds have emerged as a revolutionary drug delivery platform for promoting wound healing, due to their unique properties, including high surface area, interconnected porosity, excellent breathability, and moisture absorption, as well as their spatial structure which mimics the extracellular matrix. However, the use of nanofibers to achieve controlled drug loading and release still presents many challenges, with ongoing research still exploring how to load drugs onto nanofiber scaffolds without loss of activity and how to control their release in a specific spatiotemporal manner. This comprehensive study systematically reviews the applications and recent advances related to drug-laden nanofiber scaffolds for skin-wound management. First, we introduce commonly used methods for nanofiber preparation, including electrostatic spinning, sol-gel, molecular self-assembly, thermally induced phase separation, and 3D-printing techniques. Next, we summarize the polymers used in the preparation of nanofibers and drug delivery methods utilizing nanofiber scaffolds. We then review the application of drug-loaded nanofiber scaffolds for wound healing, considering the different stages of wound healing in which the drug acts. Finally, we briefly describe stimulus-responsive drug delivery schemes for nanofiber scaffolds, as well as other exciting drug delivery systems.

Apelin-Overexpressing Neural Stem Cells in Conjunction with a Silk Fibroin Nanofiber Scaffold for the Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries to the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin (TSF) scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a TSF nanofiber scaffold (TSFNS) that simulated the extracellular matrix in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control group, an NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and an NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence, and western blot experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and elevated the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function.

Designing an Innovative Electrospinning Strategy to Generate PHBV Nanofiber Scaffolds with a Radially Oriented Fibrous Pattern.

Electrospinning has contributed substantially to the construction of nanofibrous scaffolds for potential tissue engineering and regenerative medicine applications. However, conventional electrospinning only has the ability to generate and collect nanofiber scaffolds with a randomly oriented fibrous pattern, which lack the necessary cell alignment guidance function. In this study, a novel electrospinning fiber-collecting device was designed and developed by setting a series of small pin-ring-structured collectors on a large plain plate. Specifically, we demonstrated that the pin-ring-structured collectors, which were constructed by inserting a metal pin into the center of a metal ring, could collect the as-electrospun nanofibers with radially oriented structures in an innovative manner. We first investigated the suitable polymeric concentration for electrospinning poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and the optimum electrospinning concentration of PHBV was found to be 12% (w/v) PHBV dissolved in hexafluoroisopropyl alcohol (HFIP). Then, 12% (w/v) PHBV solution was electrospun into radially oriented nanofiber scaffolds using our novel electrospinning strategy, and their various performances were further compared with conventionally randomly oriented nanofiber scaffolds that were also produced from 12% (w/v) PHBV solution. The results showed that the radially oriented PHBV nanofiber scaffolds exhibited obviously enhanced mechanical properties and decreased hydrophobicity compared with the randomly oriented PHBV nanofiber scaffold controls. Importantly, the biological properties of radially oriented PHBV nanofiber scaffolds were also demonstrated to be enhanced, compared with randomly oriented PHBV nanofiber scaffolds, by effectively inducing cell alignment and significantly promoting cell proliferation. In sum, the present study indicates that our as-prepared nanofiber scaffolds with a radially oriented pattern are of great interest for advanced applications, such as wound dressings and tissue-engineered scaffolds.

Bioinspired Mild Photothermal Effect-Reinforced Multifunctional Fiber Scaffolds Promote Bone Regeneration.

Bone fractures are often companied with poor bone healing and high rates of infection. Early recruitment of mesenchymal stem cells (MSCs) is critical for initiating efficient bone repair, and mild thermal stimulation can accelerate the recovery of chronic diseases. Here, a bioinspired, staged photothermal effect-reinforced multifunctional scaffold was fabricated for bone repair. Uniaxially aligned electrospun polycaprolactone nanofibers were doped with black phosphorus nanosheets (BP NSs) to endow the scaffold with excellent near-infrared (NIR) responsive capability. Apt19S was then decorated on the surface of the scaffold to selectively recruit MSCs toward the injured site. Afterward, microparticles of phase change materials loaded with antibacterial drugs were also deposited on the surface of the scaffold, which could undergo a solid-to-liquid phase transition above 39 °C, triggering the release of payload to eliminate bacteria and prevent infection. Under NIR irradiation, photothermal-mediated up-regulation of heat shock proteins and accelerated biodegradation of BP NSs could promote the osteogenic differentiation of MSCs and biomineralization. Overall, this strategy shows the ability of bacteria elimination, MSCs recruitment, and bone regeneration promotion with the assistance of photothermal effect in vitro and in vivo, which emphasizes the design of a bioinspired scaffold and its potential for a mild photothermal effect in bone tissue engineering.

Preparation and In Vitro Bioactivity Study of a Novel Hollow Mesoporous Bioactive Glass Nanofiber Scaffold.

In this study, a novel three-dimensional hollow mesoporous bioactive glass nanofiber scaffold has been synthesized with a template-assisted sol-gel method using bacterial cellulose (BC) as a template and nonionic triblock copolymer (P123) as a pore-directing agent, ethyl orthosilicate (TEOS), calcium nitrate tetrahydrate (CN), and triethyl phosphate (TEP) as glass precursors. Scanning and transmission electron microscopies, X-ray diffraction, nitrogen adsorption-desorption, and nuclear magnetic resonance method were applied to characterize the morphology, crystal structure, and chemical structure of the mesoporous bioactive glass nanofiber scaffold. Furthermore, the in vitro bioactivity and biocompatibility were also explored. The obtained scaffold depicted nanofiber-like morphology and interconnected three-dimensional network structure that replicated the BC template. The scaffold showed a large specific surface area (230.0 cm2 g-1) and pore volume (0.2 m3 g-1). More importantly, the scaffold exhibited excellent apatite-forming ability and cellular biocompatibility. We believe that the hollow mesoporous bioactive glass nanofiber scaffold has great potential application in bone tissue regeneration.

Pullulan as promoting endothelialization capacity of electrospun PCL-PU scaffold.

OBJECTIVE: This project's primary purpose was to create engineered vascular scaffolds using polyurethane, polycaprolactone, and pullulan polymers, along with suitable mechanical-dynamic conditions. Therefore, electrospun scaffolds with optimized intrinsic physiological properties and the ability to support endothelial cells were prepared in vitro, and cell viability was studied in PCL-PU and PCL-PU scaffolds containing Pullulan. THE MAIN METHODS: The electrospinning method has been used to prepare PCL-PU and PCL-PU scaffolds containing Pullulan. The scaffold's surface morphology was evaluated using SEM microscopic imaging. The scaffolds' physicochemical properties were prepared using ATR-FTIR, strain stress, and water contact angle tests, and the biocompatibility of PCL-PU and PU-PCL-Pl nanofibers was evaluated using the MTT test. PRINCIPAL FINDINGS: The test results showed that PCL-PU scaffolds containing Pullulan have more suitable mechanical properties such as stress-strain, water contact angle, swelling rate, biocompatibility, fiber diameter, and pore size compared to PU-PCL. The culture of endothelial cells under static conditions on these scaffolds did not cause cytotoxic effects under static conditions compared to the control group. SEM images confirmed the ability of endothelial cells to attach to the scaffold surface. SUMMARY AND CONCLUSION: The results showed that PCL-PU substrate containing pullulan could stimulate endothelial cells' proliferation under static conditions.

Integrating Inflammation-Responsive Prodrug with Electrospun Nanofibers for Anti-Inflammation Application.

Chronic inflammation plays a side effect on tissue regeneration, greatly inhibiting the repair or regeneration of tissues. Conventional local delivery of anti-inflammation drugs through physical encapsulation into carriers face the challenges of uncontrolled release. The construction of an inflammation-responsive prodrug to release anti-inflammation drugs depending on the occurrence of inflammation to regulate chronic inflammation is of high need. Here, we construct nanofiber-based scaffolds to regulate the inflammation response of chronic inflammation during tissue regeneration. An inflammation-sensitive prodrug is synthesized by free radical polymerization of the indomethacin-containing precursor, which is prepared by the esterification of N-(2-hydroxyethyl) acrylamide with the anti-inflammation drug indomethacin. Then, anti-inflammation scaffolds are constructed by loading the prodrug in poly(ε-caprolactone)/gelatin electrospun nanofibers. Cholesterol esterase, mimicking the inflammation environment, is adopted to catalyze the hydrolysis of the ester bonds, both in the prodrug and the nanofibers matrix, leading to the generation of indomethacin and the subsequent release to the surrounding. In contrast, only a minor amount of the drug is released from the scaffold, just based on the mechanism of hydrolysis in the absence of cholesterol esterase. Furthermore, the inflammation-responsive nanofiber scaffold can effectively inhibit the cytokines secreted from RAW264.7 macrophage cells induced by lipopolysaccharide in vitro studies, highlighting the great potential of these electrospun nanofiber scaffolds to be applied for regulating the chronic inflammation in tissue regeneration.

Crimped nanofiber scaffold mimicking tendon-to-bone interface for fatty-infiltrated massive rotator cuff repair.

Electrospun fibers, with proven ability to promote tissue regeneration, are widely being explored for rotator cuff repairing. However, without post treatment, the microstructure of the electrospun scaffold is vastly different from that of natural extracellular matrix (ECM). Moreover, during mechanical loading, the nanofibers slip that hampers the proliferation and differentiation of migrating stem cells. Here, electrospun nanofiber scaffolds, with crimped nanofibers and welded joints to biomimic the intricate natural microstructure of tendon-to-bone insertion, were prepared using poly(ester-urethane)urea and gelatin via electrospinning and double crosslinking by a multi-bonding network densification strategy. The crimped nanofiber scaffold (CNS) features bionic tensile stress and induces chondrogenic differentiation, laying credible basis for in vivo experimentation. After repairing a rabbit massive rotator cuff tear using a CNS for 3 months, the continuous translational tendon-to-bone interface was fully regenerated, and fatty infiltration was simultaneously inhibited. Instead of micro-CT, µCT was employed to visualize the integrity and intricateness of the three-dimensional microstructure of the CNS-induced-healed tendon-to-bone interface at an ultra-high resolution of less than 1 µm. This study sheds light on the correlation between nanofiber post treatment and massive rotator cuff repair and provides a general strategy for crimped nanofiber preparation and tendon-to-bone interface imaging characterization.

Improved wound healing of diabetic foot ulcers using human placenta-derived mesenchymal stem cells in gelatin electrospun nanofibrous scaffolds plus a platelet-rich plasma gel: A randomized clinical trial.

AIM: The effectiveness of nanofibers containing human placenta-derived mesenchymal stem cells (hPDMSCs) plus platelet-rich plasma (PRP) for healing of diabetic foot ulcers (DFUs) was investigated. METHODS: hPDMSCs were isolated from human donor placentas, and cultured in electrospun gelatin nanofibrous scaffolds (GNS). Twenty-eight patients with DFUs were randomized into three groups in a 12-week trial: (A) Treated with hPDMSCs; (B) Treated with hPDMSCs after coating the ulcer with PRP gel; (C) Control group received standard wound care. Wound area and pain freewalkingdistance were measured every 2 weeks. RESULTS: Flow cytometry showed the expression of mesenchymal markers. SEM images and DAPI staining indicated significantly higher levels of hPDMSC proliferation on GNS after 3 and 7 days of culture. The MTS assay showed a significant increase in proliferation on GNS, compared to controls. Wound size reduction was 66% in group A, 71% in group B, and 36% in control group C. A significant difference in wound closure and pain-free walking distance was observed between groups A and B, compared to control group C (p < 0.05), but no difference between groups A and B. Biopsy of the implanted tissue showed the development of new capillary formation in groups A and B. CONCLUSION: Implantation of hPDMSCs in GNS accelerated wound healing and improved clinical parameters in DFU patients.

Concomitant Effect of Quercetin- and Magnesium-Doped Calcium Silicate on the Osteogenic and Antibacterial Activity of Scaffolds for Bone Regeneration.

Quercetin is a bioflavonoid which has a broad spectrum of biological activity. Due to its lower chemical stability, it is usually encapsulated, or a metal-quercetin complex is formed to enhance its biological activity at a lower concentration. Here, our novel approach was to form a quercetin complex to magnesium-doped calcium silicate (CMS) ceramics through a coprecipitation technique so as to take advantage of quercetin's antibacterial activity within the antibacterial and osteogenic potential of the silicate. Due to quercetin's inherent metal-chelating ability, (Ca+Mg)/Si increased with quercetin concentration. Quercetin in magnesium-doped calcium silicate ceramic showed concentration-dependent pro-oxidant and antioxidant activity in SaOS-2 with respect to quercetin concentration. By optimizing the relative concentration, we were able to achieve 3-fold higher proliferation and 1.6-fold higher total collagen at day 14, and a 1.7-fold higher alkaline phosphatase production at day 7 with respect to polycaprolactone/polyvinylpyrrolidone (PCL/PVP) scaffold. Quercetin is effective against Gram-positive bacteria such as S. aureus. Quercetin is coupled with CMS provided similar effect with lower quercetin concentration than quercetin alone. Quercetin reduced bacterial adhesion, proliferation and biofilm formation. Therefore, quercetin-coupled magnesium-doped calcium silicate not only enhanced osteogenic potential, but also reduced bacterial adhesion and proliferation.

Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway.

BACKGROUND: Epidermal stem cells (EpSCs) play a vital role in wound healing and skin renewal. Although biomaterial scaffolds have been used for transplantation of EpSCs in wound healing, the ex vivo differentiation of EpSCs limits their application. METHODS: To inhibit the differentiation of EpSCs and maintain their stemness, we developed an electrospun polycaprolactone (PCL)+cellulose acetate (CA) micro/nanofiber for the culture and transplantation of EpSCs. The modulation effect on EpSCs of the scaffold and the underlying mechanism were explored. Liquid chromatography-tandem mass spectrometry for label-free quantitative proteomics was used to analyze proteomic changes in EpSCs cultured on scaffolds. In addition, the role of transplanted undifferentiated EpSCs in wound healing was also studied. RESULTS: In this study, we found that the PCL+CA micro/nanofiber scaffold can inhibit the differentiation of EpSCs through YAP activation-mediated inhibition of the Notch signaling pathway. Significantly differentially expressed proteomics was observed in EpSCs cultured on scaffolds and IV collagen-coated culture dishes. Importantly, differential expression levels of ribosome-related proteins and metabolic pathway-related proteins were detected. Moreover, undifferentiated EpSCs transplanted with the PCL+CA scaffold can promote wound healing through the activation of the Notch signaling pathway in rat full-thickness skin defect models. CONCLUSIONS: Overall, our study demonstrated the role of the PCL+CA micro-nanofiber scaffold in maintaining the stemness of EpSCs for wound healing, which can be helpful for the development of EpSCs maintaining scaffolds and exploration of interactions between biomaterials and EpSCs.

Gas foaming of electrospun poly(L-lactide-co-caprolactone)/silk fibroin nanofiber scaffolds to promote cellular infiltration and tissue regeneration.

Electrospun nanofibers emulate extracellular matrix (ECM) morphology and architecture; however, small pore size and tightly-packed fibers impede their translation in tissue engineering. Here we exploited in situ gas foaming to afford three-dimensional (3D) poly(L-lactide-co-ε-caprolactone)/silk fibroin (PLCL/SF) scaffolds, which exhibited nanotopographic cues and a multilayered structure. The addition of SF improved the hydrophilicity and biocompatibility of 3D PLCL scaffolds. Three-dimensional scaffolds exhibited larger pore size (38.75 ± 9.78 µm2) and high porosity (87.1% ± 1.5%) than that of their 2D counterparts. 3D scaffolds also improved the deposition of ECM components and neo-vessel regeneration as well as exhibited more numbers of CD163+/CCR7+ cells after 2 weeks implantation in a subcutaneous model. Collectively, 3D PLCL/SF scaffolds have broad implications for regenerative medicine and tissue engineering applications.