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The wide-spreading of multidrug resistance poses a significant threat to human and animal health. Although antimicrobial peptides (AMPs) show great potential application, their instability has severely limited their clinical application. Here, self-assembled AMPs composed of multiple modules based on the principle of associating natural marine peptide N6 with ß-sheet-forming peptide were designed. It is noteworthy that one of the designed peptides, FFN could self-assemble into nanoparticles at 35.46 µM and achieve a dynamic transformation from nanoparticles to nanofibers in the presence of bacteria, resulting in a significant increase in stability in trypsin and tissues by 1.72-57.5 times compared to that of N6. Additionally, FFN exhibits a broad spectrum of antibacterial activity against multidrug-resistant (MDR) gram-positive (G + ) and gram-negative (G - ) bacteria with Minimum inhibitory concentrations (MICs) as low as 2 µM by membrane destruction and complemented by nanofiber capture. In vivo mouse mastitis infection model further confirmed the therapeutic potential and promising biosafety of the self-assembled peptide FFN, which can effectively alleviate mastitis caused by MDR Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and eliminate pathogenic bacteria. In conclusion, the design of peptide-based nanomaterials presents a novel approach for the delivery and clinical translation of AMPs, promoting their application in medicine and animal husbandry., (© 2024. The Author(s).)

The complex microenvironment of diabetic wounds often hinders the healing process, ultimately leading to the formation of diabetic foot ulcers and even death. Dual monitoring and treatment of wounds can significantly reduce the incidence of such cases. Herein, a multifunctional Janus membrane (3D chitosan sponge-ZE/polycaprolactone nanofibers-ZP) was developed by incorporating the zinc metal-organic framework, europium metal-organic framework, and phenol red into nanofibers for diabetic wound monitoring and treatment. The directional water transport capacity of the resulting Janus membrane allows for unidirectional and irreversible drainage of wound exudate, and the multifunctional Janus membrane creates up to a 99% antibacterial environment, both of which can treat wounds. Moreover, the pH (5-8) and H 2 O 2 (0.00-0.80 μM) levels of the wound can be monitored using the color-changing property of phenol red and the fluorescence characteristic of Eu-MOF on the obtained membrane, respectively. The healing stages of the wound can also be monitored by analyzing the RGB values of the targeted membrane images. This design can more accurately reflect the wound state and treat the wound to reduce bacterial infection and accelerate wound healing, which has been demonstrated in in vivo experiments. The results provide an important basis for early intervention in diabetic patients.

Commercial mammalian collagen-based membranes used for guided tissue regeneration (GTR) in periodontal defect repair still face significant challenges, including ethical concerns, cost-effectiveness, and limited capacity for periodontal bone regeneration. Herein, an enhanced biomimetic mineralized hydroxyapatite (HAp)-fish-scale collagen (FCOL)/chitosan (CS) nanofibrous membrane was developed. Specifically, eco-friendly and biocompatible collagen extracted from grass carp fish scales was co-electrospun with CS to produce a biomimetic extracellular matrix membrane. An enhanced biomimetic mineralized HAp coating provided abundant active calcium and phosphate sites, which promoted cell osteogenic differentiation, and showed greater in vivo absorption. In vitro experiments demonstrated that the HAp-FCOL/CS membranes exhibited desirable properties with no cytotoxicity, provided a mimetic microenvironment for stem cell recruitment, and induced periodontal ligament cell osteogenic differentiation. In rat periodontal defects, HAp-FCOL/CS membranes significantly promoted new periodontal bone formation and regeneration. The results of this study indicate that low-cost, eco-friendly, and biomimetic HAp-FCOL/CS membranes could be promising alternatives to GTR membranes for periodontal regeneration in the clinic.

Background: The purpose of dermal substitutes is to mimic the basic properties of the extracellular matrix of human skin. The application of dermal substitutes to the defect reduces the formation of hypertrophic scars and improves the scar quality. This study aims to develop an original dermal substitute enriched with stable fibroblast growth factor 2 (FGF2-STAB®) and test it in an animal model., Methods: Dermal substitutes based on collagen/chitosan scaffolds or collagen/chitosan scaffolds with nanofibrous layer were prepared and enriched with FGF2-STAB® at concentrations of 0, 0.1, 1.0, and 10.0 µg ‧ cm -2 . The performance of these dermal substitutes was tested in vivo on artificially formed skin defects in female swine. The outcomes were evaluated using cutometry at 3 and 6 months. In addition, visual appearance was assessed based on photos of the scars at 1-month, 3-month and 6-month follow-ups using Yeong scale and Visual Analog Scale., Results: The dermal substitute was fully integrated into all defects and all wounds healed successfully. FGF2-STAB®-enriched matrices yielded better results in cutometry compared to scaffolds without FGF2. Visual evaluation at 1, 3, and 6 months follow-ups detected no significant differences among groups. The FGF2-STAB® effectiveness in improving the elasticity of scar tissues was confirmed in the swine model. This effect was independently observed in the scaffolds with nanofibres as well as in the scaffolds without nanofibres., Conclusion: The formation of scars with the best elasticity was exhibited by addition 1.0 µg ‧ cm -2 of FGF2-STAB® into the scaffolds, although it had no significant effect on visual appearance at longer follow-ups. This study creates the basis for further translational studies of the developed product and its progression into the clinical phase of the research., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Wound healing is a complex process that orchestrates the coordinated action of various cells, cytokines and growth factors. Nanotechnology offers exciting new possibilities for enhancing the healing process by providing novel materials and approaches to deliver bioactive molecules to the wound site. This article elucidates recent advancements in utilizing nanoparticles, nanofibres and nanosheets for wound healing. It comprehensively discusses the advantages and limitations of each of these materials, as well as their potential applications in various types of wounds. Each of these materials, despite sharing common properties, can exhibit distinct practical characteristics that render them particularly valuable for healing various types of wounds. In this review, our primary focus is to provide a comprehensive overview of the current state-of-the-art in applying nanoparticles, nanofibres, nanosheets and their combinations to wound healing, serving as a valuable resource to guide researchers in their appropriate utilization of these nanomaterials in wound-healing research. Further studies are necessary to gain insight into the application of this type of nanomaterials in clinical settings., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of competing interest The authors declare no competing conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Intestinal adhesion is one of the complications that occurs more frequently after abdominal surgery. Postsurgical intestinal adhesion (PIA) can lead to a series of health problems, including abdominal pain, intestinal obstruction, and female infertility. Currently, hydrogels and nanofibrous films as barriers are often used for preventing PIA formation; however, these kinds of materials have their intrinsic disadvantages. Herein, we developed a dual-structure drug delivery patch consisting of poly lactic- co -glycolic acid (PLGA) nanofibers and a chitosan hydrogel (NHP). PLGA nanofibers loaded with deferoxamine mesylate (DFO) were incorporated into the hydrogel; meanwhile, the hydrogel was loaded with anti-inflammatory drug dexamethasone (DXMS). The rapid degradation of the hydrogel facilitated the release of DXMS at the acute inflammatory stage of the early injury and provided effective anti-inflammatory effects for wound sites. Moreover, PLGA composite nanofibers could provide sustained and stable release of DFO for promoting the peritoneal repair by the angiogenesis effects of DFO. The in vivo results indicated that NHP can effectively prevent PIA formation by restraining inflammation and vascularization, promoting peritoneal repair. Therefore, we believe that our NHP has a great potential application in inhibition of PIA.

Spinal cord injury (SCI) leads to massive cell death, disruption, and demyelination of axons, resulting in permanent motor and sensory dysfunctions. Stem cell transplantation is a promising therapy for SCI. However, owing to the poor microenvironment that develops following SCI, the bioactivities of these grafted stem cells are limited. Cell implantation combined with biomaterial therapies is widely studied for the development of tissue engineering technology. Herein, an insulin-like growth factor-1 (IGF-1)-bioactive supramolecular nanofiber hydrogel (IGF-1 gel) is synthesized that can activate IGF-1 downstream signaling, prevent the apoptosis of neural stem cells (NSCs), improve their proliferation, and induce their differentiation into neurons and oligodendrocytes. Moreover, implantation of NSCs carried out with IGF-1 gels promotes neurite outgrowth and myelin sheath regeneration at lesion sites following SCI. In addition, IGF-1 gels can enrich extracellular vesicles (EVs) derived from NSCs or from nerve cells differentiated from these NSCs via miRNAs related to axonal regeneration and remyelination, even in an inflammatory environment. These EVs are taken up by autologous endogenous NSCs and regulate their differentiation. This study provides adequate evidence that combined treatment with NSCs and IGF-1 gels is a potential therapeutic strategy for treating SCI., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

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., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Peripheral nerve injury (PNI) is a common clinical problem and regenerating peripheral nerve defects remain a significant challenge. Poly(polyol sebacate) (PPS) polymers are developed as promising materials for biomedical applications due to their biodegradability, biocompatibility, elastomeric properties, and ease of production. However, the application of PPS-based biomaterials in nerve tissue engineering, especially in PNI repair, is limited. In this study, PPS-based composite nanofibers poly(l-lactic acid)-poly(polycaprolactone triol-co-sebacic acid-co-N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid sodium salt) (PLLA-PPSB) are aimed to construct through electrospinning and assess their in vitro biocompatibility with Schwann cells (SCs) and in vivo repair capabilities for peripheral nerve defects. For the first time, the biocompatibility and bioactivity of PPS-based nanomaterial are examined at the molecular, cellular, and animal levels for PNI repair. Electrospun PLLA-PPSB nanofibers display favorable physicochemical properties and biocompatibility, providing an effective interface for the proliferation, glial expression, and adhesion of SCs in vitro. In vivo experiments using a 10-mm rat sciatic nerve defect model show that PLLA-PPSB nanofiber nerve conduits enhance myelin formation, axonal regeneration, angiogenesis, and functional recovery. Transcriptome analysis and biological validation indicate that PLLA-PPSB nanofibers may promote SC proliferation by activating the PI3K/Akt signaling pathway. This suggests the promising potential of PLLA-PPSB nanomaterial for PNI repair., (© 2024 Wiley‐VCH GmbH.)

Invasion of bacteria and continuous oozing of exudate are significant causes of interference with the healing of infected wounds. Therefore, an exudate-induced gelatinizable and near-infrared (NIR)-responsive nanofiber membrane composed of polyvinyl alcohol (PVA), carboxymethyl chitosan (CMC), and Fe-doped phosphomolybdic acid (Fe-PMA) with exceptional exudate absorption capacity and potent bactericidal efficacy is developed and denoted as the PVA-FP-CMC membrane. After absorbing exudate, the fiber membrane can transform into a hydrogel membrane, forming coordination bonds between the Fe-PMA and CMC. The unique exudate-induced gelation process imparts the membrane with high exudate absorption and retention capability, and the formed hydrogel also traps the bacteria that thrive in the exudate. Moreover, it is discovered for the first time that the Fe-PMA exhibits an enhanced photothermal conversion capability and photocatalytic activity compared to the PMA. Therefore, the presence of Fe-PMA provides the membrane with a photothermal and photodynamic therapeutic effect for killing bacteria. The PVA-FP-CMC membrane is proven with a liquid absorption ratio of 520.7%, a light-heat conversion efficiency of 41.9%, high-level generation of hydroxyl radical (•OH) and singlet oxygen ( 1 O 2 ), and a bacterial killing ratio of 100% for S. aureus and 99.6% for E. coli. The treatment of infected wounds on the backs of rats further confirms the promotion of wound healing by the PVA-FP-CMC membrane with NIR irradiation. Overall, this novel functional dressing for the synergistic management of bacteria-infected wounds presents a promising therapeutic strategy for tissue repair and regeneration., (© 2023 Wiley‐VCH GmbH.)

The epidermis of a deep burn wound is entirely absent and the dermal tissue sustains significant damage, accompanied by a substantial amount of tissue exudate. Due to the excessively humid environment, the formation of a scab on the wound becomes challenging, leaving it highly vulnerable to external bacterial invasion. In this work, a core-shell dual-drug-loaded nanofiber dressing was prepared by electrospinning technology for the synergistic treatment of a deep burn. The shell layer consists of polycaprolactone and chitosan encapsulating asiaticoside, with the core layer comprising the clathrate of 2-hydroxypropyl-β-cyclodextrin and curcumin. Upon application to the wound, the dual-drug-loaded nanofiber dressing exhibited rapid release of asiaticoside, stimulating collagen deposition and promoting tissue repair. The core-shell structure and clathrate configuration ensured sustained release of curcumin, providing antibacterial and anti-inflammatory functions for the wound. The mechanical strength, broad-spectrum antibacterial ability, cell proliferation, and adhesion ability of the nanofiber dressing showed its potential as a medical dressing. This dressing also exhibited excellent wound healing promoting effects in the SD rat burn model. This paper provides a strategy for burn wound healing.

Utilizing electrospun nanofibers and microneedle arrays in wound regeneration has been practiced for several years. Researchers have recently asserted that using multiple methods concurrently might enhance efficiency, despite the inherent strengths and weaknesses of each individual approach. The combination of microneedle arrays with electrospun nanofibers has the potential to create a drug delivery system and wound healing method that offer improved efficiency and accuracy in targeting. The use of microneedles with nanofibers allows for precise administration of pharmaceuticals due to the microneedles' capacity to pierce the skin and the nanofibers' role as a drug reservoir, resulting in a progressive release of drugs over a certain period of time. Electrospun nanofibers have the ability to imitate the extracellular matrix and provide a framework for cellular growth and tissue rejuvenation, while microneedle arrays show potential for enhancing tissue regeneration and enhancing the efficacy of wound healing. The integration of electrospun nanofibers with microneedle arrays may be customized to effectively tackle particular obstacles in the fields of wound healing and drug delivery. However, some issues must be addressed before this paradigm may be fully integrated into clinical settings, including but not limited to ensuring the safety and sterilization of these products for transdermal use, optimizing manufacturing methods and characterization of developed products, larger-scale production, optimizing storage conditions, and evaluating the inclusion of multiple therapeutic and antimicrobial agents to increase the synergistic effects in the wound healing process. This research examines the combination of microneedle arrays with electrospun nanofibers to enhance the delivery of drugs and promote wound healing. It explores various kinds of microneedle arrays, the materials and processes used, and current developments in their integration with electrospun nanofibers., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Poor clinical efficacy associated with postoperative hepatocellular carcinoma (HCC) often results from recurrence and metastasis. Hence, research has focused on establishing an effective multimodal therapy. However, complex combinations of active ingredients require multiple functions in therapeutic systems. Herein, a portable nanofiber patch composing germanium phosphorus (GeP) and anlotinib (AL) was designed to form a versatile platform for molecularly targeted photothermal-immune checkpoint blockade (ICB) trimodal combination therapy. The patches possess hydrophilic, satisfactory mechanical, and excellent photothermal conversion properties. Moreover, they achieve a penetrating and sustained drug release. The near-infrared light-assisted GeP-induced temperature increase regulates AL release, downregulating the expression of vascular-related factor receptors, triggering immunogenic cell death of tumor cells, and inducing dendritic cell maturation. Simultaneously, ICB therapy (programmed cell death ligand 1, PD-L1) was introduced to improve treatment outcomes. Notably, this trimodal combination therapy significantly inhibits vascular hypergrowth, enhances effector T-cell infiltration, and sensitizes the PD-L1 antibody response, boosting immunotherapy to suppress residual HCC recurrence and metastasis. Further validation of the genome sequencing results revealed cell pathways related primarily to regulatory immune effects. This study demonstrates the use of an effective and practical nanofiber patch to improve multimodal therapy of postoperative HCC, with high clinical translation value.

Nanofibers made by electrospinning have been used as bridging materials in animal models to regenerate nerves after spinal cord injury (SCI). In this meta-analysis study, we investigated the effect of these nanofibers on the motor function of animals after SCI. An extensive search in databases was performed. After primary and secondary screening, data included functional behavior, expression of glial fibrillary acidic protein, neurofilament-200 (NF-200), and β-tubulin III were taken from the articles. The quality control of the articles, statistical analysis, and subgroup analysis were performed. The results from 14 articles and 16 separate experiments showed that electrospun nanofibers used alone could improve motor behavior and reduce glial injury after SCI., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The significant clinical challenge presented by diabetic wounds is due to their impaired healing process and increased risk of complications. It is estimated that a foot ulcer will develop at some point in the lives of 15-25 % of diabetic patients. Serious complications, including infection and amputation, are often led to by these wounds. In the field of tissue engineering and regenerative medicine, nanofiber-based wound dressings have emerged in recent years as promising therapeutic strategies for diabetic wound healing. Hyaluronic acid (HA), among various nanofiber materials, has gained considerable attention due to its unique properties, including biocompatibility, biodegradability, and excellent moisture retention capacity. By promoting skin hydration and controlling inflammation, a crucial role in wound healing is played by HA. Wounds are also helped to heal faster by HA through the regulation of inflammation levels and signaling the body to build more blood vessels in the damaged area. Great potential in various applications, including wound healing, has been shown by the development and use of nanofiber formulations in medicine. However, challenges and limitations associated with nanofibers in medicine exist, such as reproducibility, proper characterization, and biological evaluation. By providing a biomimetic environment that enhances re-epithelialization and facilitates the delivery of active substances, nanofibers promote wound healing. In accelerating wound healing, promising results have been shown by HA-contained nanofiber formulations in diabetic wounds. Key strategies employed by these formulations include revascularization, modulation of the inflammation microenvironment, delivery of active substances, photothermal nanofibers, and nanoparticle-loaded fabrics. Particularly crucial is revascularization as it restores blood flow to the wound area, promoting healing. Wound healing can also be enhanced by modulating the inflammation microenvironment through controlling inflammation levels. Future perspectives in this field involve addressing the current challenges and limitations of nanofiber technology and further optimizing HA-contained nanofiber formulations for improved efficacy in diabetic wound healing. This includes exploring new fabrication techniques, enhancing the biocompatibility and biodegradability of nanofibers, and developing multifunctional nanofibers for targeted drug delivery. Not only does writing a review in the field of nanofiber-based wound dressings, particularly those containing hyaluronic acid, allow us to consolidate our current knowledge and understanding but also broadens our horizons. An opportunity is provided to delve deeper into the intricacies of this innovative therapeutic strategy, explore its potential and limitations, and envision future directions. By doing so, a contribution can be made to the ongoing advancements in tissue engineering and regenerative medicine, ultimately improving the quality of life for patients with diabetic wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The objective of this randomized clinical trial (RCT) was to assess the effectiveness of electrospun chitosan/polyvinyl alcohol (CS/PVA) nanofibrous scaffolds in preserving the alveolar ridge and enhancing bone remodeling following tooth extraction when compared to a control group. In this split RCT, 24 human alveolar sockets were randomly assigned to two groups, with 12 sockets receiving CS/PVA nanofibrous scaffold grafts (test group) and 12 left to heal by secondary intention as the control group. Cone-beam computed tomography (CBCT) was performed at two different time points: immediately after extraction (T0) and 4 months post-extraction (T4). After 4 months, linear vertical and horizontal radiographic changes and bone density of extraction sockets were assessed in both the test and control groups. The RCT included 12 patients (4 male and 8 female) with a mean age of 24 ± 3.37 years. The test group had a significantly lower mean vertical resorption vs the control group, with a mean difference of 1.1 mm (P < 0.05). Similarly, the control group's mean horizontal bone resorption was -2.01 ± 1.04 mm, while the test group had a significantly lower mean of -0.69 ± 0.41 mm, resulting in a mean difference of 1.35 mm (P < 0.05). Furthermore, the study group exhibited a significant increase in bone density (722.03 ± 131.17 HU) after 4 months compared to the control group (448.73 ± 93.23 HU). In conclusion, we demonstrated within the limitations of this study that CS/PVA nanofibrous scaffold significantly limited alveolar bone resorption horizontally and vertically and enhanced bone density in alveolar sockets after 4 months when compared to results in the control group (TCTR20230526005)., Competing Interests: Declaration of Competing interest No conflict of interest., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Postoperative recovery of cancer patients can be affected by complications, such as tissue dysfunction or disability caused by tissue resection, and also cancer recurrence resulting from residual cancer cells. Despite impressive progress made for tissue engineering scaffolds that assist tissue regeneration for postoperative cancer patients, the majority of existing tissue engineering scaffolds still lack functions for monitoring and killing residual cancer cells, if there are any, upon their detection. In this study, multifunctional scaffolds that comprise biodegradable nanofibers and core-shell structured microspheres encapsulated with theranostic nanoparticles (NPs) are developed. The multifunctional scaffolds possess an extracellular matrix-like nanofibrous architecture and soft tissue-like mechanical properties, making them excellent tissue engineering patch candidates for assisting in the repair and regeneration of tissues at the cancerous sites after surgery. Furthermore, they are capable of localized delivery of theranostic NPs upon quick degradation of core-shell structured microspheres that contain theranostic NPs. Leveraging on folic acid-mediated ligand-receptor binding, surface-enhanced Raman scattering activity, and near-infrared-responsive photothermal effect of the theranostic gold NPs (AuNPs) delivered locally, the multifunctional scaffolds display excellent active targeting, diagnosis, and photothermal therapy functions for cancer cells, showing great promise for adaptive postoperative cancer management., (© 2023 Wiley-VCH GmbH.)

Hydrogels and nanofibers have been firmly established as go-to materials for various biomedical applications. They have been mostly utilized separately, rarely together, because of their distinctive attributes and shortcomings. However, the potential benefits of integrating nanofibers with hydrogels to synergistically combine their functionalities while attenuating their drawbacks are increasingly recognized. Compared to other nanocomposite materials, incorporating nanofibers into hydrogel has the distinct advantage of emulating the hierarchical structure of natural extracellular environment needed for cell and tissue culture. The most important technological aspect of developing "nanofiber-composite hydrogel" is generating nanofibers made of various polymers that are cross-linked and short enough to maintain stable dispersion in hydrated environment. In this review, recent research efforts to develop nanofiber-composite hydrogels are presented, with added emphasis on nanofiber processing techniques. Several notable examples of implementing nanofiber-composite hydrogels for biomedical applications are also introduced., (© 2023 Wiley-VCH GmbH.)

Currently, there are no effective therapeutic targets for the treatment of chronic cerebral hypoperfusion(CCH)-induced cerebral ischemic injury. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are discovered as the inducers of neurogenesis and angiogenesis. We previously made a nanofiber membrane (NFM), maintaining a long-term release of VEGF and bFGF up to 35 days, which might make VEGF and bFGF NFM as the potential protective agents against cerebral ischemic insult. In this study, the effects of VEGF and bFGF delivered by NFM into brain were investigated as well as their underlying mechanismsin a rat model of CCH. VEGF + bFGF NFM application increased the expressions of tight junction proteins, maintained BBB integrity, and alleviated vasogenic cerebral edema. Furthermore, VEGF + bFGF NFM sticking enhanced angiogenesis and elevated CBF. Besides, VEGF + bFGF NFM treatment inhibited neuronal apoptosis and decreased neuronal loss. Moreover, roofing of VEGF + bFGF NFM attenuated microglial activation and blocked the launch of NLRP3/caspase-1/IL-1β pathway. In addition, VEGF + bFGF NFM administration prevented disruption to the pre/postsynaptic membranes and loss of myelin sheath, relieving synaptic injury and demyelination. Oligodendrogenesis, neurogenesis and PI3K/AKT/mTOR pathway were involved in the treatment of VEGF + bFGF NFM against CCH-induced neuronal injury and hypomyelination. These findings supported that VEGF + bFGF NFM application constitutes a neuroprotective strategy for the treatment of CCH, which may be worth further clinical translational research as a novel neuroprotective approach, benifiting indirect surgical revascularization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Wound healing is one of the major global health concerns in diabetic patients. Simvastatin (SMV) is a poorly soluble oral cholesterol-lowering drug that may aid diabetic wound healing. In the current study, a thixotropic peptide hydrogel of Fmoc-diphenylalanine (FmocFF) containing SMV was designed to accelerate skin wound healing effectively and safely in diabetic mice. FmocFF hydrogels were prepared at various concentrations by using the solvent-triggering technique and characterized by spectroscopic methods such as attenuated total reflection Fourier transform infrared (FT-IR) spectroscopy and fluorimetry. Mechanical behaviors were explored by oscillatory rheology. In model mice, the regenerative potential of the FmocFF-SMV hydrogel was evaluated in terms of wound contraction and closure, tissue regeneration, acute and chronic inflammation, granulation, and re-epithelization. The results showed that FmocFF-SMV hydrogels had an entangled nanofibrous microstructure and shear-thinning characteristics. FmocFF-SMV demonstrated a sustained drug release over 7 days. Compared to the unloaded FmocFF hydrogel, treatment with FmocFF-SMV led to superior diabetic wound recovery and reduced inflammation. Therefore, the utilization of the sustained-release FmocFF-SMV hydrogel formulation could become an attractive choice for topical wound therapy in diabetes patients.

Peripheral nerve injuries present significant challenges in regenerative medicine, primarily due to inherent limitations in the body's natural healing processes. In response to these challenges and with the aim of enhancing peripheral nerve regeneration, nanofiber scaffolds have emerged as a promising and advanced intervention. However, a deeper understanding of the underlying mechanistic foundations that drive the favorable contributions of nanofiber scaffolds to nerve regeneration is essential. In this comprehensive review, we make an exploration of the latent potential of nanofiber scaffolds in augmenting peripheral nerve regeneration. This exploration includes a detailed introduction to the fabrication methods of nanofibers, an analysis of the intricate interactions between these scaffolds and cellular entities, an examination of strategies related to the controlled release of bioactive agents, an assessment of the prospects for clinical translation, an exploration of emerging trends, and thorough considerations regarding biocompatibility and safety. By comprehensively elucidating the intricate structural attributes and multifaceted functional capacities inherent in nanofiber scaffolds, we aim to offer a prospective and effective strategy for the treatment of peripheral nerve injury., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Shi et al.)

Antimicrobial peptides (AMPs) are among the compounds that have significant potential to deal with infectious skin wounds. Using wound dressings or skin scaffolds containing AMPs can be an effective way to overcome infections caused by antibiotic-resistant strains. In this study, we developed an amniotic membrane-based skin scaffold using silk fibroin to improve mechanical properties and CM11 peptide as an antimicrobial peptide. The peptide was coated on the scaffold using the soaking method. The fabricated scaffold was characterised by SEM and FTIR, and their mechanical strength, biodegradation, peptide release, and cell cytotoxicity analyses were performed. Then, their antimicrobial activity was measured against antibiotic-resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. The in vivo biocompatibility of this scaffold was evaluated by subcutaneously implanting it under the skin of the mouse and counting lymphocytes and macrophages in the implanted area. Finally, the regenerative ability of the scaffold was analyzed in the mouse full-thickness wound model by measuring the wound diameter, H&E staining, and examining the expression rate of genes involved in the wound healing process. The developed scaffolds exerted an inhibiting effect on the bacteria growth, indicating their proper antimicrobial property. In vivo biocompatibility results showed no significant count of macrophages and lymphocytes between the test and control groups. The wound closure rate was significantly higher in the wound covered with fibroin electrospun-amniotic membrane loaded with 32 μg/mL CM11, where the relative expression rates of collagen I, collagen III, TGF-β1 and TGF-β3 were higher compared with the other groups., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Nanofibers (NFs) with practical drug-loading capacities, high stability, and controllable release have caught the attention of investigators due to their potential applications in on-demand drug delivery devices. Developing novel and efficient multidisciplinary management of locoregional cancer treatment through the design of smart NF-based systems integrated with combined chemotherapy and hyperthermia could provide stronger therapeutic advantages. On the other hand, implanting directly at the tumor area is a remarkable benefit of hyperthermia NF-based drug delivery approaches. Hence, implantable smart hyperthermia NFs might be very hopeful for tumor treatment in the future and provide new avenues for developing highly efficient localized drug delivery systems. Indeed, features of the smart NFs lead to the construction of a reversibly flexible nanostructure that enables hyperthermia and facile switchable release of antitumor agents to eradicate cancer cells. Accordingly, this study covers recent updates on applications of implantable smart hyperthermia NFs regarding their current scope and future outlook. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants., (© 2023 Wiley Periodicals LLC.)

Retinal ischemia is involved in the occurrence and development of various eye diseases, including glaucoma, diabetic retinopathy, and central retinal artery occlusion. To the best of our knowledge, few studies have reported self-assembling peptide natural products for the suppression of ocular inflammation and oxidative stress. Herein, a self-assembling peptide GFFYE is designed and synthesized, which can transform the non-hydrophilicity of rhein into an amphiphilic sustained-release therapeutic agent, and rhein-based therapeutic nanofibers (abbreviated as Rh-GFFYE) are constructed for the treatment of retinal ischemia-reperfusion (RIR) injury. Rh-GFFYE significantly ameliorates oxidative stress and inflammation in an in vitro oxygen-glucose deprivation (OGD) model of retinal ischemia and a rat model of RIR injury. Rh-GFFYE also significantly enhances retinal electrophysiological recovery and exhibits good biocompatibility. Importantly, Rh-GFFYE also promotes the transition of M1-type macrophages to the M2 type, ultimately altering the pro-inflammatory microenvironment. Further investigation of the treatment mechanism indicates that Rh-GFFYE activates the PI3K/AKT/mTOR signaling pathway to reduce oxidative stress and inhibits the NF-κB and STAT3 signaling pathways to affect inflammation and macrophage polarization. In conclusion, the rhein-loaded nanoplatform alleviates RIR injury by modulating the retinal microenvironment. The findings are expected to promote the clinical application of hydrophobic natural products in RIR injury-associated eye diseases., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Osteoarthritis (OA) is a prevalent global health concern, posing a significant and increasing public health challenge worldwide. Recently, nanotechnology-boosted biomaterials have emerged as a highly promising strategy for OA therapy due to their exceptional physicochemical properties and capacity to regulate pathological processes. However, there is an urgent need for a deeper understanding of the potential therapeutic applications of these biomaterials in the clinical management of diseases, particularly in the treatment of OA. In this comprehensive review, we present an extensive discussion of the current status and future prospects concerning nanotechnology-boosted biomaterials for OA therapy. Initially, we discuss the pathophysiology of OA and the constraints associated with existing treatment modalities. Subsequently, various types of nanomaterials utilized for OA therapy, including nanoparticles, nanofibers, and nanocomposites, are thoroughly discussed and summarized, elucidating their respective advantages and challenges. Furthermore, we analyze recent preclinical and clinical studies that highlight the potential of nanotechnology-boosted biomaterials in OA therapy. Additionally, future research directions in this evolving field are highlighted. By establishing a link between the structural properties of nanotechnology-boosted biomaterials and their therapeutic functions in OA treatment, we aim to foster advances in designing sophisticated nanomaterials for OA, ultimately resulting in improved therapeutic efficacy of OA therapy through translation into clinical setting in the near future., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Liu et al.)

The regeneration of cutaneous tissue is one of the most challenging issues in human regenerative medicine. To date, several studies have been done to promote cutaneous tissue healing with minimum side effects. The healing potential of polyurethane (PU)/Poly (caprolactone)-poly (ethylene glycol)-poly (caprolactone) (PCEC)/chitosan (CS) (PCS) nanofibrous mat with cationic photosensitizer meso tetrakis (N-methyl pyridinium-4-yl) porphyrin tetratosylate salt (TMP) was examined. The CS tripolyphosphate nanoparticles (CSNPs) were prepared and loaded by TMP to provide an efficient drug release system (TMPNPs) for delivery of TMP to promote wound healing. In in vitro setting, parameters such as bactericidal effects, cytocompatibility, and hemolytic effects were examined. The healing potential of prepared nanofibrous mats was investigated in a rat model of full-thickness cutaneous injury. PCS/TMP/TMPNPs nanofibers can efficiently release porphyrin in the aqueous phase. The addition of TMPNPs and CS to the PU backbone increased the hydrophilicity, degradation, and reduced mechanical properties. The culture of human fetal foreskin fibroblasts (HFFF2) on PCS/TMP/TMPNPs scaffold led to an increased survival rate and morphological adaptation analyzed by MTT and SEM images. Irradiation with a red laser (635 nm, 3 J/cm 2 ) for the 30 s reduced viability of S. aureus and E. Coli bacteria plated on PCS/TMP and PCS/TMP/TMPNPs nanofibrous mats compared to PU/PCEC (PC) and PU/PCEC/CS (PCS) groups, indicating prominent antibacterial effects of PCS/TMP and PCS/TMP/TMPNPs nanofibrous (p < 0.05). Data indicated that PCS/TMP/TMPNPs mat enhanced healing of the full-thickness excisional wound in a rat model by the reduction of inflammatory response and fibrotic changes compared to the PC, and PCS groups (p < 0.05). Immunofluorescence imaging indicated that levels of Desmoglein were increased in rats that received PCS/TMP/TMPNPs compared to the other groups. It is found that a PU-based nanofibrous mat is an appropriate scaffold to accelerate the healing of injured skin., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Short designer self-assembling peptide (dSAP) biomaterials are a new addition to the hemostat group. It may provide a diverse and robust toolbox for surgeons to integrate wound microenvironment with much safer and stronger hemostatic capacity than conventional materials and hemostatic agents. Especially in noncompressible torso hemorrhage (NCTH), diffuse mucosal surface bleeding, and internal medical bleeding (IMB), with respect to the optimal hemostatic formulation, dSAP biomaterials are the ingenious nanofiber alternatives to make bioactive neural scaffold, nasal packing, large mucosal surface coverage in gastrointestinal surgery (esophagus, gastric lesion, duodenum, and lower digestive tract), epicardiac cell-delivery carrier, transparent matrix barrier, and so on. Herein, in multiple surgical specialties, dSAP-biomaterial-based nano-hemostats achieve safe, effective, and immediate hemostasis, facile wound healing, and potentially reduce the risks in delayed bleeding, rebleeding, post-operative bleeding, or related complications. The biosafety in vivo, bleeding indications, tissue-sealing quality, surgical feasibility, and local usability are addressed comprehensively and sequentially and pursued to develop useful surgical techniques with better hemostatic performance. Here, the state of the art and all-round advancements of nano-hemostatic approaches in surgery are provided. Relevant critical insights will inspire exciting investigations on peptide nanotechnology, next-generation biomaterials, and better promising prospects in clinics., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Diabetic wounds impose enormous distress and financial burden on patients, and finding effective dressings to manage wounds is critical. As a Chinese herbal medicine with a long history of Clinical application, Bletilla striata has significant medicinal effects in the therapy of various wounds. In this study, PLA and the pharmacodynamic substances of Bletilla striata were prepared into fibrous scaffolds by emulsion electrospinning technology for the management of diabetic wounds in mice. The results of scanning electron microscopy showed that the core-shell structure fibre was successfully obtained by emulsion electrospinning. The fibre membrane exhibited excellent water absorption capability and water vapor transmission rate, could inhibit the growth of Staphylococcus aureus and Pseudomonas aeruginosa , had good compatibility, and achieved excellent healing effect on diabetic wounds. Especially in the in vivo wound healing experiment, the wound healing rate of composite fibre membrane treatment reached 98.587 ± 2.149% in 16 days. This work demonstrated the good therapeutic effect of the developed fibrous membrane to diabetic wound, and this membrane could be potentially applied to chronic wound healing.

Diabetic foot ulcer (DFU) healing has long been a major medical challenge. The type of dressing is an essential factor in wound healing, prevention of local infection, and scar formation. Today, smart wound dressings or wound healing patches can precisely control drug delivery to the target tissue and prevent this significant complication. Nanofiber (NF) wound dressings are effective in reducing wound scarring and helping to speed up the healing process for DFU. The electrospun NFs have a suitable surface topography, density, and three-dimensional structure, which can be considered an efficient method to produce a substrate for tissue engineering and wound healing. Chitosan (CS) is one of the most well-known biopolymers in wound healing tissue engineering and drug delivery systems. The unique properties of CS make it suitable for biomedical applications. Based on new studies in the field of hemostatic and antimicrobial effects of CS in controlling bleeding and wound healing and application of NF wound dressings, the purpose of this study is a review relevant works on CS-based NFs to improve the DFU., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Currently employed approaches and materials used for vital pulp therapies (VPTs) and regenerative endodontic procedures (REPs) lack the efficacy to predictably achieve successful outcomes due to their inability to achieve adequate disinfection and/or lack of desired immune modulatory effects. Natural polymers and medicinal herbs are biocompatible, biodegradable, and present several therapeutic benefits and immune-modulatory properties; thus, standing out as a clinically viable approach capable of establishing a conducive environment devoid of bacteria and inflammation to support continued root development, dentinal bridge formation, and dental pulp tissue regeneration. However, the low stability and poor mechanical properties of the natural compounds have limited their application as potential biomaterials for endodontic procedures. In this study, Aloe vera (AV), as a natural antimicrobial and anti-inflammatory agent, was incorporated into photocrosslinkable Gelatin methacrylate (GelMA) nanofibers with the purpose of developing a highly biocompatible biomaterial capable of eradicating endodontic infection and modulating inflammation. Stable GelMA/AV nanofibers with optimal properties were obtained at the ratio of (70:30) by electrospinning. In addition to the pronounced antibacterial effect against Enterococcus faecalis, the GelMA/AV (70:30) nanofibers also exhibited a sustained antibacterial activity over 14 days and significant biofilm reduction with minimal cytotoxicity, as well as anti-inflammatory properties and immunomodulatory effects favoring healing. Our results indicate that the novel GelMA/AV (70:30) nanofibers hold great potential as a biomaterial strategy for endodontic infection eradication and enhanced healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Drug delivery and delivery systems are among the most important research disciplines today, and the relevance of nanofibers in achieving the appropriate release profile at specified sites for increased therapeutic advantages cannot be understated. Nanofiber-based drug delivery systems are fabricated and modified using a range of methods that entail a variety of factors and processes; tuning of these allows control of the drug release such as targeted, extended, multistage, and stimuli-responsive release. We explore nanofiber-based drug delivery systems from the most recent accessible literature, focusing on materials, techniques, modifications, drug release, applications, and challenges. This review offers a thorough assessment of the current and future potential of nanofiber-based drug delivery systems, with a particular emphasis on their capabilities in stimuli-responsive and dual drug delivery. The review begins with an introduction to the important characteristics of nanofibers that are useful in drug delivery applications, followed by materials and synthesis procedures for various types of nanofibers, as well as their practicality and scalability. The review then focuses on and explores the modification and functionalization strategies of nanofibers as essential features for regulating the applications of nanofibers in drug loading, transport, and release. Finally, this review investigates the range of nanofiber-based drug delivery systems in satisfying the current requirements by pointing out the areas that need improvement, followed by critical analysis, and offers probable solutions.

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFβ) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFβ/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA., (© 2023 Wiley-VCH GmbH.)

Wound dressings with outstanding biocompatibility, antimicrobial, and tissue regeneration activities are essential to manage emerging recalcitrant antifungal infections to speed up healing. In this study, we have engineered p -cymene-loaded gellan/PVA nanofibers using electrospinning. Morphological and physicochemical properties of the nanofibers were characterized using a multitude of techniques to validate the successful integration of p -cymene ( p -cym). The fabricated nanomaterials exhibited strong antibiofilm activity against Candida albicans and Candida glabrata compared to pure p -cymene. In vitro biocompatibility assay demonstrated that nanofibers did not possess any cytotoxicity to the NIH3T3 cell lines. In vivo , full-thickness excision wound healing study showed that the nanofibers were able to heal skin lesions faster than the conventional clotrimazole gel in 24 days without forming any scar. These findings unraveled p -cymene-loaded gellan gum (GA)/poly(vinyl alcohol) (PVA) nanofibers as an effective biomaterial for cutaneous tissue regeneration.

Wound dressings have been designed to provide the optimal environment to fibroblasts, keratinocytes, and macrophages to promote wound healing while inhibiting potential microbial infection. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel with a gelatin backbone that contains natural cell binding motifs such as arginine-glycine-aspartic acid (RGD) and MMP-sensitive degradation sites, making it an ideal material for wound dressing. However, GelMA alone is unable to stably protect the wound and regulate cellular activities due to its weak mechanical properties and nonmicropatterned surface, limiting its application as a wound dressing. Herein, we report the development of a hydrogel-nanofiber composite wound dressing utilizing GelMA and poly(caprolactone) (PCL)/gelatin nanofiber, which can systematically manage the skin regeneration process with an enhanced mechanical property and micropatterned surface. GelMA sandwiched between electrospun aligned and interlaced nanofibers that mimic epidermis and dermis layers, respectively, increased the stiffness of the resulting hydrogel composite with a comparable swelling rate as GelMA. Fabricated hydrogel composite was determined to be biocompatible and nontoxic. In addition to the beneficial effect of GelMA in accelerating wound healing, subsequent histological analysis revealed upregulated re-epithelialization of granulation tissue and deposition of mature collagen. Hydrogel composite interacted with fibroblasts to regulate their morphology, proliferation, and collagen synthesis, as well as the expression of α-SMA, TGF-β, and collagen I and III during the wound healing process both in vitro and in vivo . Taken together, we propose hydrogel/nanofiber composite as a wound dressing of the next generation that can induce skin tissue layer regeneration beyond the basic wound closure promotion of present dressings.

Silk fibroin (SF), extracted from Bombyx mori, has unique physicochemical properties to achieve an efficient wound dressing. In this study, reduced graphene oxide (RGO)/ZnO NPs/silk fibroin nanocomposite was made, and an innovative nanofiber of SF/polyvinyl alcohol (PVA)/RGO/ZnO NPs was ready with the electrospinning technique and successfully characterized. The results of MIC and OD analyses were used to investigate the synthesized materials' antibacterial effects and displayed that the synthesized materials could inhibit growth against Staphylococcus aureus and Escherichia coli bacteria. However, both in vitro cytotoxicity (MTT) and scratch wound studies have shown that RGO/ZnO NPs and SF/PVA/RGO/ZnO NPs are not only non-toxic to NIH 3T3 fibroblasts, but also can cause cell viability, cell proliferation, and cell migration. Furthermore, improving the synthesized nanofiber's structural properties in the presence of RGO and ZnO NPs has been confirmed by performing tensile strength, contact angle, and biodegradation analyses. Also, in a cell attachment analysis, fibroblast cells had migrated and expanded well in the nanofibrous structures. Moreover, in vivo assay, SF/PVA/RGO/ZnO NPs nanofiber treated rats and has been shown significant healing activity and tissue regeneration compared with other treated groups. Therefore, this study suggests that SF/PVA/RGO/ZnO NPs nanofiber is a hopeful wound dressing for preventing bacteria growth and improving superficial wound repair., (© 2023 American Institute of Chemical Engineers.)

Introduction: Researchers aim for new heights in wound healing to produce wound dressings with unique features. Natural, synthetic, biodegradable, and biocompatible polymers especially in the nanoscale are being employed to support and provide efficient wound management. Economical and environmentally friendly sustainable wound management alternatives are becoming an urgent issue to meet future needs. Nanofibrous mats possess unique properties for ideal wound healing. They mimic the physical structure of the natural extracellular matrix (ECM), promote hemostasis, and gas permeation. Their interconnected nanoporosity prevents wound dehydration and microbial infiltration., Purpose: To prepare and evaluate a novel verapamil HCl-loaded environmentally friendly composite, with biopolymer-based electrospun nanofibers suitable for application as wound dressings providing adequate wound healing with no scar formation., Methods: Composite nanofibers were prepared by electrospinning of a blend of the natural biocompatible polymers, sodium alginate (SA) or zein (Z) together with polyvinyl alcohol (PVA). Composite nanofibers were characterized in terms of morphology, diameter, drug entrapment efficiency, and release. In vivo study of the therapeutic efficacy of verapamil HCl-loaded nanofibers on a Sprague Dawley rat model with dermal burn wound was investigated in terms of percent wound closure, and presence of scars., Results: Combining PVA with SA or Z improved the electrospinnability and properties of the developed nanofibers. Verapamil HCl-loaded composite nanofibers showed good pharmaceutical attributes favorable for wound healing including, fiber diameter ∼150 nm, high entrapment efficiency (∼80-100%) and biphasic controlled drug release for 24 h. In vivo study demonstrated promising potentials for wound healing without scaring., Conclusion: The developed nanofibrous mats combined the beneficial properties of the biopolymers and verapamil HCl to provide an increased functionality by exploiting the unique advantages of nanofibers in wound healing at a small dose proved to be insufficient in case of the conventional dosage form., Competing Interests: The authors declare that they have no relevant financial or non-financial conflict of interests to disclose., (© 2023 Barakat et al.)

The current treatment strategies for diabetic wound care provide only moderate degree of effectiveness; hence new and improved therapeutic techniques are in great demand. Diabetic wound healing is a complex physiological process that involves synchronisation of various biological events such as haemostasis, inflammation, and remodelling. Nanomaterials like polymeric nanofibers (NFs) offer a promising approach for the treatment of diabetic wounds and have emerged as viable options for wound management. Electrospinning is a powerful and cost-effective method to fabricate versatile NFs with a wide array of raw materials for different biological applications. The electrospun NFs have unique advantages in the development of wound dressings due to their high specific surface area and porosity. The electrospun NFs possess a unique porous structure and biological function similar to the natural extracellular matrix (ECM), and are known to accelerate wound healing. Compared to traditional dressings, the electrospun NFs are more effective in healing wounds owing to their distinct characteristics, good surface functionalisation, better biocompatibility and biodegradability. This review provides a comprehensive overview of the electrospinning procedure and its operating principle, with special emphasis on the role of electrospun NFs in the treatment of diabetic wounds. This review discusses the present techniques applied in the fabrication of NF dressings, and highlights the future prospects of electrospun NFs in medicinal applications., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Diabetic wound healing has attracted widespread attention in biomedical engineering. However, the harsh hypoxic microenvironment (HME) comprising high glucose levels, local bleeding, and bacterial infection often leads to the formation of hyperplastic scars, increasing the clinical demand for wound dressings. Here, we report a comprehensive strategy using near-infrared NIR-assisted oxygen delivery combined with the bioactive nature of biopolymers for remodeling the HME. Black phosphorus (BP) nanosheets and hemoglobin (Hb) were self-assembled layerwise onto electrospun poly-l-lactide (PLLA) nanofibers using charged quaternized chitosan (QCS) and hyaluronic acid. BP converts NIR radiation into heat and stimulates Hb to release oxygen in situ. QCS is a hemostatic and broad-spectrum antibacterial material. Moderate BP-derived photothermal therapy can increase the sensitivity of bacteria to QCS. A series of composite wound dressings (coded as PQBH-n) with different numbers of layers were fabricated, and the in vivo diabetic wound healing potentials were tested. The molecular mechanism can be partly attributed to the cytokine-cytokine receptor interaction. Notably, this comprehensive strategy based on NIR-assisted oxygen delivery combined with the bioactive properties of biopolymers is not only applicable for fabricating multifunctional wound dressings but also has a great potential in expanding biomedical engineering fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bioresponsive nanodrug delivery systems have excellent potential in tissue engineering applications. Poly-anionic and poly-cationic biopolymers have provided a superior platform for designing pH-sensitive drug delivery systems. In this regard, hyaluronic acid-chitosan-polyvinyl alcohol complex nanofibers with high quality and reproducibility were produced by optimizing the solution preparation process. In addition, the synthesized composite nanofiber, with 66.82 kN/mm toughness, 200% swelling ratio, and 60% porosity, exhibited excellent properties to meet the requirements of the ideal wound dressing. Green cross-linking with citric acid prevented the destruction of the nanofiber even after prolonged immersion in biological solutions. ζ potential studies demonstrated that the synthesized nanofiber has a negative surface charge (∼-30) at physiological pH. The p K a of the temporin-Ra peptide is about 10, and as a result the peptide molecules have a net positive charge in physiological conditions. Therefore, peptide molecules immobilized on the synthesized scaffold based on surface adsorption. In vivo evaluation has proven that the wound bed has an alkaline environment, facilitating peptide release from the nanofiber scaffold. Electrospun nanofibers can imitate the architecture of the extracellular matrix for accelerating wound healing. In vitro investigation showed better adhesion, proliferation, migration, and fibroblast cell growth on peptide-loaded nanofiber samples than other groups. In vivo studies on full-thickness wounds in the mouse model indicated that the designed nanofiber was gradually absorbed without causing dryness or infection. On day 6, the peptide-loaded nanofiber revealed 60% wound closure compared to the control group (17%). In addition, based on histological studies, the composite nanofiber demonstrated excellent tissue repair ability, hence these active nanofiber mats can be a good alternative to existing wound dressings. Gene expression studies show that the antimicrobial peptide promotes the inflammatory phase of wound healing in a shorter time frame by accelerating the tumor necrosis factor-α cytokine response.

Cancer remains one of the most challenging health problems worldwide, and localized therapeutic approaches based on micro/nanofibers have shown potential for its treatment. Micro/nanofibers offer several advantages as a drug delivery system, such as high surface area, tunable pore size, and sustained release properties, which can improve drug efficacy and reduce side effects. In addition, functionalization of these fibers with nanoparticles can enhance their targeting and therapeutic capabilities. Localized delivery of drugs and/or other therapeutic agents via micro/nanofibers can also help to overcome the limitations of systemic administration, such as poor bioavailability and off-target effects. Several studies have shown promising results in preclinical models of cancer, including inhibition of tumor growth and improved survival rates. However, more research is needed to overcome technical and regulatory challenges to bring these approaches to clinical use. Localized therapeutic approaches based on micro/nanofibers hold great promise for the future of cancer treatment, providing a targeted, effective, and minimally invasive alternative to traditional treatments. The main focus of this review is to explore the current treatments utilizing micro/nanofibers, as well as localized drug delivery systems that rely on fibrous structures to deliver and release drugs for the treatment of cancer in a specific area.

The study reveals the polymer-crosslinker interactions and functionality of hydrophilic nanofibers for antibacterial wound coatings. Coaxial electrospinning leverages a drug encapsulation protocol for a core-shell fiber composite with a core derived from polyvinyl alcohol and polyethylene glycol with amorphous silica (PVA-PEG-SiO 2 ), and a shell originating from polyvinyl alcohol and graphene oxide (PVA-GO). Crosslinking with GO and SiO 2 initiates the hydrogel transition for the fiber composite upon contact with moisture, which aims to optimize the drug release. The effect of hydrogel-inducing additives on the drug kinetics is evaluated in the case of chlorhexidine digluconate (CHX) encapsulation in the core of core-shell fiber composite PVA-PEG-SiO 2 -1x-CHX@PVA-GO. The release rate is assessed with the zero, first-order, Higuchi, and Korsmeyer-Peppas kinetic models, where the inclusion of crosslinking silica provides a longer degradation and release rate. CHX medicated core-shell composite provides sustainable antibacterial activity against Staphylococcus aureus .

An anti-adhesive barrier membrane incorporating hyaluronic acid (HA) can reduce fibroblasts attachment and impart lubrication effect for smooth tendon gliding during management of post-surgical tendon adhesion. On the other hand, as numerous growth factors are required during tendon recovery, growth factors released by platelets in platelet-rich plasma (PRP) can provide beneficial therapeutic effects to facilitate tendon recovery post tendon injury. Furthermore, PRP is reported to be associated with anti-inflammatory properties for suppressing postoperative adhesion. Toward this end, we fabricate core-shell nanofiber membranes (NFM) with HA/PRP-infused core and polycaprolactone shell in this study. Different NFM with 100 % (H-P), 75 % (HP31-P), 50 % (HP11-P) and 25 % (H31-P) HA in the core was fabricated through coaxial electrospinning and analyzed through microscopic, pore size, mechanical, as well as HA and growth factor release studies. In vitro study with fibroblasts indicates the NFM can act as a barrier to prevent cell penetration and reduce cell attachment/focal adhesion, in addition to promoting tenocyte migration in tendon healing. In vivo studies in a rabbit flexor tendon rupture model indicates the HP11-P NFM shows improved efficacy over H-P NFM and control in reducing tendon adhesion formation and inflammation, while promoting tendon healing, from functional assays and histological analysis., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Small-diameter blood vascular transplantation failure is mainly caused by the vascular materials' unreliable hemocompatibility and histocompatibility and the unmatched mechanical properties, which will cause unstable blood flow. How to solve the problems of coagulation and intimal hyperplasia caused by the above factors is formidable in vascular replacement. In this work, we have synthesized poly(ferulic acid) (PFA) and prepared poly(ester-urethane)urea (PEUU)/silk fibroin (SF)/poly(ferulic acid) (PFA) hybrid nanofibers vascular graft (PSPG) by random electrospinning and post-double network bond crosslinking for process optimization. The results in vitro demonstrated that the graft is of significant anti-oxidation, matched mechanical properties, reliable cytocompatibility, and blood compatibility. Replacing resected rat abdominal aorta and rabbit carotid artery models with PSPG vascular grafts indicated that the grafts are capable of homogeneous hybrid PFA significantly promoted the stabilization of endothelial cells and the ingrowth of smooth muscle cells, meanwhile stabilizing the immune microenvironment. This research demonstrates the PSPG vascular graft with substantial patency, indicating their potential for injured vascular healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of tissue engineering scaffolds is of great significance for the repair and regeneration of damaged tissues and organs. Silk fibroin (SF) is a natural protein polymer with good biocompatibility, biodegradability, excellent physical and mechanical properties and processability, making it an ideal universal tissue engineering scaffold material. Nanofibers prepared by electrospinning have attracted extensive attention in the field of tissue engineering due to their excellent mechanical properties, high specific surface area, and similar morphology as to extracellular matrix (ECM). The combination of silk fibroin and electrospinning is a promising strategy for the preparation of tissue engineering scaffolds. In this review, the research progress of electrospun silk fibroin nanofibers in the regeneration of skin, vascular, bone, neural, tendons, cardiac, periodontal, ocular and other tissues is discussed in detail., (© 2022 Wiley-VCH GmbH.)

Acute myocardial infarction (AMI), which cut down blood flow to the myocardium, is a serious health-threatening disorder that causes remarkable morbidity and mortality. To date, scaffolds have opened new prospects for potential applications for cardiac regeneration after AMI. The hybrid scaffolds as novel strategies can improve the performance of scaffolds. Chitosan is a naturally safe copolymer with good biocompatibility and biodegradability. Recently, chitosan-based formulations have attracted a lot of interest for scaffolds fabrication. Regarding, chitosan-based hybrid scaffolds have a wide application in cardiac tissue regeneration. This review is focused on the recent progression of the various biodegradable chitosan hybrid-based scaffolds (hydrogels, nanofibers, patch) that have been designed for cardiac engineering. Besides, we discussed, in short, the future perspective and challenges of these types of scaffolds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Nanofiber wound dressings remain the domain of in vitro studies. The purpose of our study was to verify the benefits of chitosan (CTS) and polylactide (PLA)-based nanofiber wound dressings on a porcine model of a naturally contaminated standardized wound and compare them with the conventional dressings, i.e., gauze and Inadine., Material and Methods: The study group included 32 pigs randomized into four homogeneous groups according to the wound dressing type. Standardized wounds were created on their backs, and wound dressings were regularly changed. We evaluated difficulty of handling individual dressing materials and macroscopic appearance of the wounds. Wound swabs were taken for bacteriological examination. Blood samples were obtained to determine blood count values and serum levels of acute phase proteins (serum amyloid A, C-reactive protein, and haptoglobin). The crucial point of the study was histological analysis. Microscopic evaluation was focused on the defect depth and tissue reactions, including formation of the fibrin exudate with neutrophil granulocytes, the layer of granulation and cellular connective tissue, and the reepithelialization. Statistical analysis was performed by using SPSS software. The analysis was based on the Kruskal-Wallis H test and Mann-Whitney U test followed by Bonferroni correction. Significance was set at P < .05., Results: Macroscopic examination did not show any difference in wound healing among the groups. However, evaluation of histological findings demonstrated that PLA-based nanofiber dressing accelerated the proliferative (P = .025) and reepithelialization (P < .001) healing phases, while chitosan-based nanofiber dressing potentiated and accelerated the inflammatory phase (P = .006). No statistically significant changes were observed in the blood count or acute inflammatory phase proteins during the trial. Different dynamics were noted in serum amyloid A values in the group treated with PLA-based nanofiber dressing (P = .006)., Conclusion: Based on the microscopic examination, we have documented a positive effect of nanofiber wound dressings on acceleration of individual phases of the healing process. Nanofiber wound dressings have a potential to become in future part of the common wound care practice., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A Non-healing infected wound is an ever-growing global epidemic, with increasing burden of mortality rates and management costs. The problems of chronic wound infections and their outcomes will continue as long as their underlying causes like diabetic wounds grow and spread. Commercial wound therapies employed have limited potential that inhibits pivotal functions and tissue re-epithelialization properties resulting in wound infections. Nanomaterial based drug delivery formulations involving biological macromolecules are developing areas of interest in wound healing applications which are utilized in the re-epithelialization of skin with cost-effective preparations. Research conducted on nanofibers has shown enhanced skin establishment with improved cell proliferation and growth and delivery of bioactive organic molecules at the wound site. However, drug targeted delivery with anti-scarring properties and tissue regeneration aspects have not been updated and discussed in the case of macromolecule impregnated nanofibrous mats. Hence, this review focuses on the brief concepts of wound healing and wound management, therapeutic commercialized wound dressings currently available in the field of wound care, effective electrospun nanofibers impregnated with different biological macromolecules and advancement of nanomaterials for tissue engineering have been discussed. These new findings will pave the way for producing anti-scarring high effective wound scaffolds for drug delivery., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Any interference in the timely and orderly progression through all the phases of healing process can turn a minor injury into a chronic wound. Most of the wound dressings available in the market are moderately effective and have not shown satisfactory improvement in healing. Along with the appropriate wound management, it is imperative for a dressing to facilitate the wound repair process too. In the present research, we hypothesize to improve the wound healing process by applying cost effective natural cocktail of various bioactive factors. Bovine colostrum contains high levels of immunoglobulins, lactoferrin, hormones and cytokines which play significant role in wound healing. Hence, multifunctional colostrum conjugated PCL-PEG based nanofibrous dressings were developed and analyzed for their physicochemical properties and cellular responses. The dressings were also evaluated for cell migration, antioxidant, anti-inflammatory and anti-bacterial properties. In-vivo wound healing ability was validated on a rat wound model. Numerous growth factors present in the colostrum showed their role in stimulation of skin repair and regeneration by direct action on genetic material. Significantly less inflammation in colostrum treated wounds was observed due to anti-inflammatory properties of lactoferrin. Thus obtained results confirmed the suitability of these multifunctional colostrum conjugated nanofibrous dressings for improved wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)