Persistent inflammation and infection within a macerated microenvironment critically hinder skin wound healing. Here, we report an engineered to regulate liquid transport and promote wound repair. The composite consists of a hydrophobic top layer, a hydrophilic gel-forming middle layer, and two drug-loaded fibrous layers with tunable hydrophobicity. This gradient architecture from hydrophobic to hydrophilic layers integrates directional liquid transport, efficient water absorption, breathability, and mechanical robustness. The diode-like liquid transport behavior enables pH-responsive, dual-drug release, providing synergistic anti-inflammatory and antibacterial effects. Consequently, this design minimizes maceration while maintaining a moist, bioactive environment favorable for tissue regeneration. Both in vitro and in vivo studies confirm the composite's pronounced antioxidant and hemostatic activities, along with its ability to markedly reduce infection and inflammation, thereby accelerating wound closure and promoting new tissue formation. This work presents a multifunctional therapeutic platform and highlights the significant clinical potential of this hierarchical composite for advanced wound management.

Pectin has great application potential, but the effect of molecular weight on its physicochemical properties remains unclear. In this study, high‑molecular‑weight pectin (HMP, 425 000 Da) and low‑molecular‑weight pectin (LMP, 186 936 Da) were prepared from pomelo peel, a major food-processing by-product, by ultrasound‑assisted extraction and enzymatic depolymerization, respectively. Comprehensive characterization revealed pronounced molecular-weight-dependent differences. SEM and AFM revealed distinct morphologies, while XPS and FTIR confirmed comparable elemental composition and characteristic functional groups for both pectin fractions. The degree of methyl esterification was 83.42% for HMP and 65.0% for LMP. XRD indicated lower local chain ordering in HMP. Furthermore, LMP showed exhibited enhanced pH-responsive surface charge behavior, displaying a more negative ζ-potential in the weakly acidic to neutral pH range (5.0–7.0), together with a smaller particle size distribution (295–458 nm) compared with HMP (458–1000 nm). Whereas, HMP exhibited higher water absorbing capacity (305.8%) than LMP (253.8%). These results demonstrate that molecular weight is a critical determinant of pectin physicochemistry, governing chain organization, surface charge behavior, hydration dynamics, and functional performance, and provide a rational framework for the valorization of citrus by-products in the design of functional pectin-based biomaterials for food, pharmaceutical, and healthcare applications.

Nerve guidance conduits (NGCs) represent a promising alternative to autologous nerve transplantation; however, their clinical efficacy remains limited by insufficient structural integrity and suboptimal fascicular guidance. Here, we report a novel extrusion-stretched strategy for fabricating multigrooved NGCs (MNGCs) reinforced with oriented multiwalled carbon nanotubes (MWCNTs). This scalable and controllable method effectively prevents conduit collapse during fabrication and enables precise regulation of conduit geometry, overcoming key limitations of conventional forming approaches. Incorporation of MWCNTs significantly enhanced the mechanical strength and biocompatibility of the conduits, as evidenced by improved Schwann cell (RSC96) viability, density, and pronounced aligned elongation compared with pure polycaprolactone (PCL) conduits. In a rat sciatic nerve defect model, the MWCNT-reinforced multigrooved NGCs (MMNGCs) achieved functional recovery, gastrocnemius muscle regeneration, and axonal myelination comparable to autografts while markedly outperforming single-lumen and groove-only PCL conduits. These results demonstrate that MMNGCs fabricated via the proposed extrusion-stretched strategy constitute a highly effective and clinically competitive platform for peripheral nerve repair.

Nerve guidance conduits (NGCs) effectively support and guide the regeneration of injured nerves. However, traditional NGCs often lack essential growth factors and fail to create a biomimetic microenvironment conducive to nerve regrowth. This study develops a highly bionic nerve guidance conduit (HB-NGC) using hybrid high-voltage electrotechnologies that integrate electrospinning with electrohydrodynamic (EHD) printing. The outer layer consists of electrospun polycaprolactone fibers loaded with carboxyl-multi-walled carbon nanotubes, while the inner layer is composed of highly aligned polycaprolactone fibers created by EHD printing. The tubular core of the HB-NGC is filled with hyaluronic acid methacryloyl (HAMA) hydrogel encapsulating bone marrow mesenchymal stem cells (BMSCs). This highly biomimetic NGC is conductive, capable of guiding axon growth, and sustainably releases growth factors, effectively mimicking the structure, function, and characteristics of natural peripheral nerves. Its distinctive architectural layers provide an exceptional bionic microenvironment by restoring physical pathways, facilitating electrical signal conduction, and supplying an extracellular matrix (ECM) environment enriched with essential growth factors. Additionally, the HB-NGC’s morphology, along with its physicochemical and mechanical properties, effectively bridges the gap between severed nerve ends. In vivo animal studies validate the HB-NGC’s effectiveness, highlighting its significant potential to enhance peripheral nerve regeneration.

Nerve guidance conduits capable of wireless stimulation represent a promising approach for addressing peripheral nerve defects. However, traditional electrical stimulation methods are not sufficiently convenient and may cause secondary damage. In this study, a conductive nerve guidance conduit combined with wireless electrical stimulation using alternating magnetic fields is presented. The conduit coated with nanographene and incorporated with Fe3O4 nanoparticles induces currents and creates a supportive microenvironment enhancing nerve regeneration. Finite element analysis confirms that the conduit generates electromotive force under an external alternating magnetic field. The conduit exhibits improved morphology, physicochemical properties, and conductivity by six orders of magnitude. In vitro experiments demonstrate that the conduit promotes Schwann cell proliferation, migration, and intercellular communication through microcurrents, as well as neuronal axon extension. TEM images confirm axon extension and myelin sheath thickness, indicating its high conductivity and efficiency in promoting nerve regeneration across defects. In vivo studies show that the conduit generated microcurrent using wireless electromagnetic stimulation, significantly enhancing myelin restoration, gastrocnemius muscle regeneration, motor function recovery, and nerve tissue growth, achieving results comparable to the gold-standard autograft method. Overall, this work highlights the effectiveness of electromagnetic induction in nerve repair and presents a new, non-invasive stimulation for peripheral nerve regeneration.

Wound healing, a crucial process for all individuals, is often hindered by limited skin donors, bacterial infections, and imprecise drug delivery. This study demonstrates an innovative biomimetic 3D composite scaffold with pH-responsive micropatterns that replicates the hierarchical biostructure of natural skin through hybrid electrotechnologies. The engineered microstructure not only prevents bacterial infections but also possesses biomimetic physical, chemical, and mechanical properties of natural skin, creating an infiltration gradient to meet the distinct moisture requirements of the epidermis and dermis, while ensuring appropriate water absorption, breathability, and hydrophobicity. Moreover, the composite scaffold triggered by exudate in response to pH changes within the wound enables precise drug release for localized treatment. In vivo assays confirm the biomimetic 3D composite scaffold with pH-responsive micropatterns as a potential skin substitute for expediting wound healing.

Background: Recently, the use of the tumor or its secretions as drug carriers has gradually become popular, with the advantages of high biocompatibility and enhanced drug delivery to specific cells. Melanoma is the most malignant tumor of all skin cancers; it is the most metastatic and, therefore, the most difficult to treat. The main purpose of this study is to develop nanovesicles with tumor cell membrane secretion properties to encapsulate target substances to enhance the therapeutic effect of cancer. Methods: Astaxanthin was selected as an anticancer drug due to our previous research finding that astaxanthin has extremely high antioxidant, anti-ultraviolet damage, and anti-tumor properties. The manufacturing method of the astaxanthin nanovesicle carrier is to mix melanoma cells and astaxanthin in an appropriate ratio and then remove the genetic material and inflammatory factors of cancer cells by extrusion. Results: In terms of results, after the co-culture of astaxanthin nanovesicles and melanoma cancer cells, it was confirmed that the ability of astaxanthin nanovesicles to inhibit the growth and metastasis of melanoma cancer cells was significantly better than the same amount of astaxanthin alone, and it had no effect on normal Human cells are also effective. There was no apparent harm on normal cells, indicating the ability of the vesicles to be selectively transported. Conclusion: Our findings illustrated the potential of astaxanthin nanovesicles as an anticancer drug.

BACKGROUND:Critical bone defects pose a significant challenge for orthopedic surgeons. Autologous bone grafting is the golden standard. However, it is hindered by issues such as donor site morbidity and limited availability. Commercially available artificial bone grafts may encounter challenges in properly integrating the surrounding bone tissue, potentially leading to delayed or incomplete healing. Furthermore, magnesium deficiency has been shown to negatively affect localized angiogenesis and bone repair. As a result, creating a synthetic biomaterial that includes magnesium could serve as an excellent bone substitute. The study aims to evaluate and test the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM). METHODS:This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. RESULTS:The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 min and a compressive strength of 4.39 ± 0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. CONCLUSION:In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.

Background: Melanoma, the uncontrolled accumulation of malignant melanocytes, remains one of the most dangerous and deadly types of skin cancer. Current medical interventions, such as radiation and immunotherapy, are ineffective in treating malignant metastatic melanoma of the lung. Due to the complexity of cancer, abnormalities occur and lead to treatment failure. Methods: In this study, a novel, dual-reaction hydrogel was composed of a thermo-sensitive type (fundamental) and a pH-sensitive type. In addition, the innovative hydrogel showed thermal reversibility and could liquefy at low temperatures and recover at room temperature. We used Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis (TGA), and rheometer to observe the hydrogel's mechanical properties. Significant findings: Results show the hydrogel had a small pore size, revealing positive interactions between molecular chains. The dual-reactive hydrogel exhibited the least cytotoxicity to B16F10 cells in vitro, indicating great biocompatibility and potential. The hydrogel in microparticles brings several advantages, including a high surface area-to-volume ratio and delivery within microscale structures. Microfluidic devices are promising for producing hydrogel particles because they enable high-precision flow control during microfabrication, resulting in precise size and shape. This study used a microfluidic device to produce hydrogel particles and encapsulate cells for future drug screening applications.

The present study aimed to develop miconazole nitrate solid lipid nanoparticle (SLN) loaded polymeric microneedle (MN) patches (SPs) via the vacuum micromolding approach. The SLNs were fabricated through melt emulsification of stearic acid using Tween 80. SPs were prepared using chitosan, gelatin (as base materials) and polyethylene glycol 400 (as a plasticizer). The prepared formulations were evaluated for various physicochemical parameters, including particle size, polydispersity index, encapsulation efficiency, loading capacity (in the case of SLNs), folding endurance, % swelling and insertion ability (in the case of SPs). Scanning electron microscopy and differential scanning calorimetry (DSC) studies were carried out for morphological and thermal analysis, respectively. Phase analysis was carried out via X-ray diffraction (XRD). In vitro tensile strength, drug release, anti-biofilm activity and in vivo anti-biofilm activity were studied to assess the efficiency of the SLN loaded polymeric formulation. Miconazole nitrate containing SLNs appeared as smooth-surfaced aggregates and displayed a particle diameter of ∼224 nm, polydispersity index of ∼0.32, encapsulation efficiency of ∼88.88% and loading capacity of ∼8.88%. SPs exhibited evenly aligned, uniform-surfaced, sharp-tipped projections, with an acceptable folding endurance of ∼300 and % swelling of ∼359%. DSC and XRD results confirmed the incorporation of the drug within the solidified lipid matrix as an amorphous solid. The miconazole nitrate lipidic nanoparticle containing polymeric formulation exhibited a tensile strength ∼1.35 times lower than the pure drug loaded counterpart. During in vitro studies, SPs released ∼94% miconazole nitrate within 150 minutes and reduced the mass of the Candida albicans (C. albicans) biofilm by ∼79%. After 10 days of treatment with SPs, C. albicans infected wounds were healed, confirming that the prepared formulations can be used for the management of fungal biofilms.

Multi-channeled nerve guidance conduit is a prospective way to repair peripheral nerve injury, which is still difficult to be fabricated. A novel extrusion-stretching method was utilized in this study to produce multi-walled carbon nanotubes (MWCNTs) loaded multi-channeled nerve conduits with improved flexibility and versatility. The channels and geography of the conduits were tunable. The results showed that the mechanical properties of the multi-channeled nerve conduits were suitable for peripheral nerve restoration. MWCNTs increased the biocompatibility of the multi-channeled nerve conduits. This study proved that the MWCNTs loaded multi-channeled produced by extrusion-stretching method have great potential to repair peripheral nerve injury.

Peripheral nerve regeneration and functional recovery rely on the chemical, physical, and structural properties of nerve guidance conduits (NGCs). However, the limited support for long-distance nerve regeneration and axonal guidance has hindered the widespread use of NGCs. This study introduces a novel nerve guidance conduit with oriented lateral walls, incorporating multi-walled carbon nanotubes (MWCNTs) within core-shell fibers prepared in a single step using a modified electrohydrodynamic (EHD) printing technique to promote peripheral nerve regeneration. The structured conduit demonstrated exceptional stability, mechanical properties, and biocompatibility, significantly enhancing the functionality of NGCs. In vitro cell studies revealed that RSC96 cells adhered and proliferated effectively along the oriented fibers, demonstrating a favorable response to the distinctive architectures and properties. Subsequently, a rat sciatic nerve injury model demonstrated effective efficacy in promoting peripheral nerve regeneration and functional recovery. Tissue analysis and functional testing highlighted the significant impact of MWCNT concentration in enhancing peripheral nerve regeneration and confirming well-matured aligned axonal growth, muscle recovery, and higher densities of myelinated axons. These findings demonstrate the potential of oriented lateral architectures with coaxial MWCNT fibers as a promising approach to support long-distance regeneration and encourage directional nerve growth for peripheral nerve repair in clinical applications.

Fibre alignment technology is crucial in various emerging applications, such as drug delivery systems, tissue engineering, and scaffold fabrication. However, conventional methods have limitations when it comes to incorporating aligned fibres into 3D printed structures in situ. This research demonstrates the use of custom designed templates made with conductive ink to control the alignment of drug-loaded polymer fibres on a 3D printed microscale structure. Three different geometries were designed, and the effects of the template on fibre diameter and pattern were investigated. The hybrid structure demonstrated successful control of aligned fibres on printed structures using grounded conductive ink geometric electrodes, as confirmed by SEM. All three custom-designed templates presented unique geometric alignments and fibre diameters of around 1 & mu;m. Additionally, the different collector shapes had an impact on the distribution of fibre diameters. FTIR and EDX analyses concluded that the drug was effectively encapsulated throughout the fibres. In-situ deposition of fibres onto the 3D printed structure enhanced the mechanical properties, and water contact angle results showed that the hybrid structure transitioned to a hydrophilic state with the addition of fibres. A drug delivery study confirmed that the hybrid structure functions as a steady release system, following a Korsmeyer-Peppas kinetic release model. TGA results indicated that the samples are thermally stable, and DSC analysis concluded that the samples were homogeneously produced. The results obtained from the hybrid structures provide a novel mechanism for integrating aligned fibres and 3D printed structures for development in fields such as biomedical engineering, regenerative medicine, and advanced manufacturing.

Flexible devices have been rapidly developed and applied in various applications. However, there have been few reports on printable graphene-based sensors with customized structures and properties capable of respiratory and airflow monitoring. In this study, a graphene-based flexible sensor with a conical microdot array (GSCA) made by the direct-ink writing 3D printing method for real-time personal signals and air-coupled detection is reported. GSCA 3D structures with microdot features on the sensing layer can deliver a fast response of below 60 ms and improve the sensitivity by 32.4% (26-78 kPa), 800% (78-102 kPa), and 600% (102-160 kPa) by adjusting the printing parameters. The sensor exhibits a low detection limit of 11.4 Pa and a large detection range with a linear sensitivity of 1.4-509 kPa. The spider leg-like micro-/nanofibers between two adjacent microdots contribute to electron transport and airflow sensing. The results show the feasibility of the graphene-based sensor with dots to recognize air strength and direction for respiration and airflow. Further validation of the GSCA in real-time personal monitoring demonstrates the potential for multitasking wearable sensors.

The blood-brain barrier (BBB) is a protective element of the neurovascular unit (NVU) surrounded by astrocytes, pericytes, extracellular matrix, and the tight junctional complex, which play a fundamental role in brain homeostasis. Due to its impeccable structural architecture, the BBB is referred to as the brain's gatekeeper, a near-impenetrable barrier to therapeutics. This review summarises the significant strides that have been made in the last 5 years towards circumventing the BBB and developing efficient drug delivery systems. Challenges associated with several CNS disorders related to BBB failure and exploitation of this unique NVU component for targeted treatment of brain-related disorders are also discussed.

Corneal abrasion is a common traumatic emergency, which can cause eyelid photophobia, tearing, and obvious foreign body sensation and pain. Herein, the 3D contact lens‐like chloramphenicol‐loaded patches composed of well‐organized micrometer fibers are prepared via electrohydrodynamic (EHD) printing to treat corneal abrasions. The main material of these patches is cellulose acetate (CA), and chloramphenicol (CAM) is loaded in the patches. EHD printing can realize micrometer fibers stacked layer by layer to form a customizable shape suitable for eye wear. Herein, the surface morphology, chemical as well as physical properties, transparency, drug release behaviors, and biocompatibility of the patches loading various concentrations of CAM are studied. It is found that the CAM‐loaded patches have 3D hemispherical shape similar to contact lens and smooth surface morphology. Moreover, patches loaded with different concentrations of CAM all maintain good water absorption, hydrophilicity, light transmittance, and biocompatibility. The drug release curves of CAM‐loaded patches show that the contact lens‐like patches have high loading efficiency and can achieve sustained release of CAM, indicating clinical potential in the treatment of corneal abrasions.

Treatment of microbial biofilms by conventional topical dosage forms remains a challenge due to the presence of extracellular polymeric substances, necrotic tissues and cellular debris. An advanced drug delivery system such as a microarray patch can breach these barriers and deliver antimicrobial agents to deep-seated pathogens. This study aimed to fabricate gentamicin sulphate laden dissolving microarray patches, comprising of sodium hyaluronate, gelatin, polyvinyl alcohol and D-sorbitol, by using vacuum micromoulding approach. Morphological and phase analysis of patches were carried out by scanning electron microscopy, and differential scanning calorimetry (DSC), X-ray diffraction (XRD), respectively. In silico analysis was performed to study the molecular interactions between substrates (sodium hyaluronate and gelatin) and enzymes (hyaluronate lyase and gelatinase). In vitro insertion ability, stimulus-responsiveness, drug release study, antimicrobial assay, antibiofilm activity and in vivo antibiofilm activity were performed to assess the efficiency of prepared formulation. The patches displayed sharp-tipped, uniform-surfaced and equidistant microprojections. DSC and XRD results revealed that the microarray patch is an amorphous solid. In silico analysis indicated non-covalent interactions between substrates and enzymes. In vitro insertion test confirmed piercing ability of microarrays. Stimulus i.e., enzymes hyaluronate lyase and gelatinase responsiveness of sodium hyaluronate and gelatin, respectively was confirmed by liquefaction of media. During in vitro release study, 96 +/- 2.6% antibiotic was released within 150 min. The patches exhibited antibacterial effect against Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Salmonella enterica (S. enterica). The biomass of S. aureus and P. aeruginosa biofilms was significantly reduced (>= 70%), in vitro, following treatment with antibiotic laden patches. S. aureus infected wounds were completely healed after 11 days of treatment with prepared patches. In conclusion, fabricated microarray patches can be used for an on-site stimulus responsive administration of gentamicin sulphate and management of S. aureus infected cutaneous wounds.

The directional growth of Schwann cell can promote the repair of peripheral nerve injury (PNI) and aligned fibers have been proved to promote the directional growth of Schwann cell. However, the preparation of nerve guidance conduits (NGCs) composed of aligned fibers is still a challenge. The aim of this study was to develop a highly aligned NGCs composed of coaxial fibers via a novel one-step modified electrohydrodynamic (EHD) printing method. Multi-walled carbon nanotubes (MWCNTs) were incorporated into the polycaprolactone (PCL) as the outer layer of coaxial fibers, and polyethylene oxide (PEO) was as the core of the fibers. In this study, the effects of the concentration of MWCNTs and the coaxial structure on the performance of the NGCs were evaluated systematically. The results showed that the aligned MWCNTs loaded NGCs composed of coaxial fibers had excellent performance in nerve regeneration and functional recovery while providing suitable mechanical support for nerve regrowth when the loading concentration of MWCNTs was 1%. Therefore, the aligned MWCNTs loaded NGCs composed of coaxial fibers offers essential insights into the preparation of traditional NGCs and highlighted its potential in clinical application.

Dental caries is the most common chronic infectious disease in the human oral cavity and current anti-caries drugs may cause drug resistance and microecological imbalance. In this study, a sandwich-structured electrospun pH-responsive dental paste was engineered via the layer-by-layer electrospinning technique. The top and bottom layers of the dental paste were pH-sensitive layers prepared with Methylmethacrylate polymers IV (E100), and the middle layer was the polylactic acid (PLA) membrane loading with sodium fluorides (NaF). Herein, the surface morphology, chemical as well as physical properties, drug release behaviors, biocompatibility and antibacterial properties of the dental paste were investigated. It was found that the sandwich liked structure enhanced the mechanical properties of the dental paste. The drug release curves of NaF-loaded dental pastes showed that NaF released rapidly and massively in the simulated oral fluid with a risk of dental caries. While in the simulated healthy oral fluid, NaF released slowly and in small amounts. And the dental paste maintained excellent hydrophobic, biocompatibility and antibacterial properties against Streptococcus mutans. Therefore, this sandwich-structured dental paste could respond to pH environment and achieve anti-caries smartly, indicating clinical potential in caries prevention.