Meniscus regeneration remains challenging due to insufficient mechanical support and complex inflammatory microenvironment. We developed a mechanically stable, immunomodulatory composite short-fiber scaffold, CSI-PE, for functional meniscus repair. The scaffold was engineered by incorporating homogenized poly-L-lactic acid (PLLA)/decellularized meniscus extracellular matrix (dmECM) short fibers (designated as PE fibers for PLLA/dmECM) into a chitosan-ibuprofen (CS-IBU) conjugate matrix, followed by glutaraldehyde cross-linking and lysine modification. CSI-PE exhibited an interconnected porous structure with a porosity greater than 80%, providing excellent fatigue resistance and withstanding 100 compression cycles, providing essential mechanical stability for early-stage tissue integration. It enabled sustained IBU release for up to 56 days (67 ± 5 μg/mg), effectively modulating the immune microenvironment by reducing reactive oxygen species (ROS) production and promoting macrophage polarization. This immunomodulatory microenvironment synergistically enhanced the proliferation, migration, and fibrocartilaginous differentiation of bone marrow mesenchymal stem cells (BMSCs) under adverse conditions. In vivo, CSI-PE significantly alleviated intra-articular inflammation and facilitated high-quality tissue regeneration with well-organized collagen deposition while preventing cartilage degeneration after 8 weeks. Transcriptomic analysis further associated this regeneration with immune regulation and extracellular matrix remodeling pathways. This strategy effectively harmonizes mechanical stability with immune homeostasis, positioning CSI-PE as a promising candidate for meniscus tissue engineering.
Meniscus injuries present dual challenges, including limited regenerative capacity due to avascularity and a persistent inflammatory microenvironment following injury. Herein, we reported a decellularized meniscus extracellular matrix (dmECM) scaffold functionalized with a hyaluronic acid (HA) and celecoxib (CLX) grafted (dmECM-HC) through carbodiimide chemistry. This design integrates acute immunomodulation with long-term regenerative support. The dmECM scaffold recapitulated the ECM architecture of the native meniscus, while the HA-CLX enhanced its elasticity and immunomodulatory capacity. The dmECM-HC scaffold exhibited superior mechanical performance retention during 1000 cyclic compression cycles and demonstrated sustained release of CLX for up to 7 weeks in vitro. It promoted M2 polarization of lipopolysaccharide (LPS)-stimulated macrophages and effectively modulated acute inflammation through Toll-like receptor, tumor necrosis factor (TNF), and Nuclear factor kappa-B (NF-κB) signaling pathways. Together with its robust antioxidant capacity, the dmECM-HC scaffold provided a pro-regenerative microenvironment. Furthermore, it significantly facilitated stem cell recruitment and ECM deposition. In a rabbit meniscus defect model, the dmECM-HC scaffold promoted tissue repair by activating NF-κB and calcium signaling pathways. At 12 weeks, it significantly enhanced tissue maturation and collagen arrangement in the defect area and mitigated cartilage degeneration. This strategy guides meniscus healing with a dual function by modulating the inflammatory environment while providing biomimetic structural support.
Central airway obstruction (CAO), as a common clinically critical disease, poses significant challenges in its treatment. For some patients unable to undergo surgical treatment, airway stent implantation is a key alternative therapy. In this study, polycaprolactone (PCL) was used to fabricate the airway stents, which were individually customized through 3D printing technology. Polyethyleneimine (PEI) was then used for surface cross-linking to produce aminated PCL stents, and the anti-inflammatory drug ibuprofen (IBU) was loaded on the surface of the aminated stents through covalent cross-linking. The stent (PCL-IBU) exhibits good mechanical properties, excellent biocompatibility, and remarkable anti-inflammatory effects. In vitro, the PCL-IBU stent can effectively regulate the expression of inflammatory genes and inhibit the production of key inflammatory factors. In a rat subcutaneous embedding experiment, compared to ordinary PCL stents, it can significantly reduce the inflammatory response at the implantation site. This study provides preliminary evidence for optimizing postoperative inflammation using 3D-printed personalized anti-inflammatory stents, demonstrating potential to overcome limitations of conventional stents (particularly regarding severe postoperative inflammation) and offering a novel strategy for airway stenosis repair.
The increasing aging of the population has elevated bone defects to a significant threat to human life and health. Aerogel, a biomimetic material similar to an extracellular matrix (ECM), is considered an effective material for the treatment of bone defects. However, most aerogel scaffolds suffer from immune rejection and poor anti-inflammatory properties and are not well suited for human bone growth. In this study, we used electrospinning to prepare flexible ZnO-SiO2 nanofibers with different zinc concentrations and further assembled them into three-dimensional composite aerogel scaffolds. The prepared scaffolds exhibited an ordered pore structure, and chitosan (CS) was utilized as a cross-linking agent with aspirin (ASA). Interestingly, the 1%ZnO-SiO2/CS@ASA scaffolds not only exhibited good biocompatibility, bioactivity, anti-inflammation, and better mechanical properties but also significantly promoted vascularization and osteoblast differentiation in vitro. In the mouse cranial defect model, the BV/TV data showed a higher osteogenesis rate in the 1%ZnO-SiO2/CS group (10.94 ± 0.68%) and the 1%ZnO-SiO2/CS@ASA group (22.76 ± 1.83%), compared with the control group (5.59 ± 2.08%), and in vivo studies confirmed the ability of 1%ZnO-SiO2/CS@ASA to promote in situ regeneration of new bone. This may be attributed to the fact that Si4+, Zn2+, and ASA released from 1%ZnO-SiO2/CS@ASA scaffolds can promote angiogenesis and bone formation by stimulating the interaction between endothelial cells (ECs) and BMSCs, as well as inducing macrophage differentiation to the M2 type and downregulating the expression of pro-inflammatory factor (TNF-α) to modulate local inflammatory response. These exciting results and evidence suggest that it provides a new and effective strategy for the treatment of bone defects.
Peripheral nerve injury (PNI) often leads to disability and chronic pain, with limited options available to promote regeneration and functional recovery. Bone marrow mesenchymal stem cells (BMSCs) are considered promising candidates for cell therapy in PNI repair. However, the effective induction of BMSCs towards neurogenesis and the directed migration of cells remain challenging. Here, we constructed a biomimetic environment by combining uniaxially aligned polycaprolactone (PCL) nanofibers containing silica nanoparticles (SiO2 NPs) with electrical stimulation (ES). A proper portion of SiO2 NPs was uniformly integrated into uniaxially aligned PCL nanofibers to create nanoscale protrusions on fiber surfaces. Such fibrous mats showed uniaxially aligned morphology, uniform fiber diameter, and improved wettability. BMSCs were then cultured on both the nanofibers with smooth surfaces (PCL) or those decorated with nanoscale protrusions (PCL/SiO2), followed by treatment with or without ES, with glass slides used as a control. All the fibrous mats showed good cell viability, and the uniaxially aligned fibers induced better cell extension and alignment in comparison to the control group. Both the contact guidance provided by the nanoscale protrusions on fiber surfaces and the biochemical signal from ES contributed to BMSC differentiation, with a combination of both promoting the greatest differentiation into neural-like cells. Immunofluorescence micrographs demonstrated significantly increased expression of NF200 and S100β, along with a higher proportion of NF200‑positive cells compared with S100β, indicating the preferred differentiation of BMSCs to neuron-like cells under such conditions. Additionally, in migration assays the greatest number and longest migration distance of BMSCs were exhibited on the PCL/SiO2 nanofibers with ES. These studies offer valuable strategies for the manipulation of stem cell behavior in PNI repair.
Conductive and anti-inflammatory microenvironments have been proven effective for peripheral nerve repair. Herein, a conductive chitosan-hydroxyethyl cellulose/ionic liquid (CS-HEC/IL) hydrogel was constructed, which was injected into a hollow anti-inflammatory poly(L-lactide-co-caprolactone)/luteolin (PLCL/Lut) nanofiber conduit. Such a PLCL/Lut-CS-HEC/IL conduit greatly enhanced the proliferation of Schwann and PC12 cells, andpromotedmacrophage transition to the M2 phenotype. Following implantation into a 10 mm sciatic nerve defect in a rat model, the scaffold was harvested 8 weeks post-surgery for histological and functional assessment. Histological analysis revealed that the conduit markedly enhanced nerve regeneration, as indicated by extensive myelination and axonal outgrowth, while functional assessments indicated improved motor recovery and nerve conduction, highlighting its therapeutic potential. Generally, the PLCL/Lut-CS-HEC/IL scaffold is a promising therapeutic strategy for peripheral nerve injuries.
Peripheral nerve injury usually results in motor and sensory impairments, with nerve guidance conduits (NGCs) representing a promising strategy to facilitate nerve regeneration. The recovery of peripheral nerve injury is critically influenced by the topographic guidance cues and electrical properties of NGCs. In this study, the combination of hydroxyethyl cellulose (HEC) and poly(3,4-ethylenedioxythiophene) (PEDOT) was used for the first time to enhance the conductivity of conduits. Through electrospinning, spiral-structured conductive PLCL/ HEC-PEDOT NGCs filled with aligned nanofibers (F-P/H-P) were fabricated. These electrospun F-P/H-P NGCs exhibited superior electrical conductivity, which significantly enhanced the adhesion and proliferation of SCs and PC12 cells and further promoted the expression of S100 and NF200 proteins in combination with electrical stimulation. In vivo experiments utilizing sciatic nerve defect models revealed that the conductive F-P/H-P conduit significantly accelerated peripheral nerve regeneration, neovascularization, and functional recovery. This study demonstrates the potential of electrospun conductive NGCs filled with aligned nanofiber membranes (F-P/H-P) to promote peripheral nerve regeneration and functional restoration.
Currently, the repair of Achilles tendon sleeve avulsion is a challenge due to their limited research and particularly difficult treatment. In tendon repair surgery, the construction of bone tunnels is required for the suspensory fixation of ruptured tendon by sutures. However, due to the biologically inert of commonly used tendon sutures, postoperative fixation instability, bone tunnel enlargement, and even tendon reconstruction failure can easily occur under stressful conditions. In this study, core-spun nanoyarns containing β-tricalcium phosphate (β-TCP) were prepared by electrospinning to serve as surgical sutures for tendon traction and fixation. The suture of 6 core-spun nanoyarns spun again into one strand had stronger mechanical properties, which could effectively pull the tendon. The silk fibroin micron yarn of the suture core layer and the polycaprolactone/silk fibroin/β-TCP nanofibers of the shell layer demonstrated favorable biocompatibility, which facilitated cell adhesion and expression in the tendon and bone. In the repair surgery of the Achilles tendon sleeve avulsion in rabbits, compared with non-degradable and high mechanical properties commercial sutures, the β-TCP in the nanofibers of sutures could induce osteogenesis, thereby reducing the gap in the bone tunnel and preventing enlargement of the bone tunnel. In conclusion, the suture could weave the ruptured tendon, fix the tendon to the bone, promote the formation of new bone in the bone tunnel, avoid the instability of the existing commercial sutures to the bone tunnel, and ultimately improve the success rate of tendon repair surgery. STATEMENT OF SIGNIFICANCE: Nowadays, there is very limited research on the Achilles tendon sleeve avulsion model. This model presents challenges due to inadequate tendon tissue in the calcaneus for direct repair and insufficient bone tissue on the avulsed tendon for fixation. The incidence of this model is low, but treatment once it occurs is particularly difficult. In this study, we proposed to compound osteogenesis-promoting β-TCP materials onto nanoyarns to prepare surgical sutures that could weave the ruptured tendon, fix the tendon to the bone, induce osteogenesis, and reduce the gap in the bone tunnel, thus avoiding the instability of the existing commercial sutures in the bone tunnel, and ultimately improving the success rate of the surgery.
Clinically, gingival tissue repair is challenging due to the complex oral microbial environment and inflammation. The development of gingival membranes using tissue engineering techniques offers a promising solution to this issue. This study focuses on developing a nanofibrous gingival membrane, combining polylactic acid (PLA), decellularized extracellular matrix (dECM), and magnesium oxide (MgO) nanoparticles. Electrospinning was used to fabricate membranes with varying ratios of PLA, dECM, and MgO, and their mechanical, antibacterial, and cell-proliferation properties were evaluated. NIH-3T3 and rat gingival fibroblast (RGF) cells were cultured on the membranes to assess biocompatibility. A rat model with gingival defects was used to test in vivo tissue regeneration. It was indicated that the antibacterial nanofibrous membranes with MgO showed enhanced antibacterial effects and reduced inflammation, and promoted gingival tissue repair.
Achilles tendon sleeve avulsions often involve tissue defects. Standard bone tunnel fixation risks tunnel enlargement, inflammation, and graft failure. Native tendon and bone tissue exhibit inherent bioelectrical properties whose disruption impedes healing. To address these, the study developed electroactive, anti-inflammatory sutures featuring a strong polylactic acid (PLA) micron yarn core and a conductive poly(3,4-ethylenedioxythiophene)/hydroxyethyl cellulose/glycerol/chondroitin sulfate/PLA (PEDOT/HEC/glycerol/CS/PLA) nanofibrous shell. A novel synthesis strategy enabled EDOT polymerization templated by HEC, eliminating the need for poly(styrene sulfonate) (PSS), oxidants, or catalysts and allowing direct electrospinning. In vitro, it can regulate macrophage polarization and enhance tenocytes and bone marrow mesenchymal stem cell (BMSCs) proliferation and differentiation. In a rabbit Achilles tendon avulsion model, the suture enables secure tendon-to-bone fixation via calcaneal bone tunnels. At 12 weeks post-operation, the suture exerts anti-inflammatory effects by modulating CD206/CD86 expression. Electroactive suture significantly enhances tendon regeneration and bone formation within the tunnels, and achieves robust tendon-to-bone integration at the interface, markedly improving fixation stability. In summary, this electroactive, anti-inflammatory suture effectively promotes tendon-bone regeneration for repairing Achilles tendon sleeve avulsions.
Nano-biochar (nano-BC) is one of the most active fractions in the BC continuum and frequently detected in terrestrial ecosystems. However, a paucity of information exists on reactivity and environmental functions of nano-BC in the rhizosphere. The present study investigated the potential of nano-BC in transforming silver ions (Ag+) to silver nanoparticles (AgNPs) in the rhizosphere of rice. We found that the synergistic effect of nano-BC and dioxygen secreted from rice roots was essential for Ag⁺ reduction to AgNPs. In this process, nano-BC transferred electrons to dioxygen, resulting in the formation of superoxide free radicals, which subsequently donate electrons to Ag+. Notably, excess nano-BC was unfavorable to dioxygen secretion from roots and thus inhibited the formation of AgNPs. Our results highlight that although nano-BC significantly decreased the uptake of Ag by rice plants, it contributed to the accumulation of AgNPs in plant tissues. TEM and single-particle ICP-MS analyses confirmed the presence of AgNPs not only in intercellular spaces of leaf tissues but also within the interior of leaf cells. These findings indicate that nano-BC plays a critical role in regulating the chemical species and bioaccumulation of redox-active metals (such as Ag) in the rhizosphere, which has important implications for element cycling from the pedosphere to terrestrial vegetation and warrants further investigation.
For clinical treatment of end-stage renal disease (ESRD) patients, the development of vascular grafts possessing both puncture resistance and anticoagulant properties remains crucial for arteriovenous fistula establishment. In this study, small-diameter vascular conduits were engineered through electrospinning of polyurethane (PU) microfibers, incorporating polyethylene coil reinforcement within the graft wall architecture to confer kink resistance. The microporous structure of the grafts demonstrated effective self-sealing capabilities following needle perforation. Additionally, heparin immobilization was implemented on the luminal surface to optimize thromboresistance. Large animal implantation studies revealed that the PU vascular grafts exhibited immediate puncture feasibility, superior puncture durability, and maintained excellent hemodynamic patency in vivo, demonstrating significant translational potential for clinical hemodialysis applications.
Tendons are connective tissues with a regular three-dimensional structure containing collagen fibers, and the oriented collagen fibril gives tendons a piezoelectric effect. After tendon injury or rupture, the native electrical microenvironment in which it is located is disrupted, and the electrical signal pathway is blocked. Electrical stimulation (ES) can guide cell orientation, promote tissue differentiation, and enhance tendon repair. Therefore, bioactive materials that generate ES are ideal for repairing tendons by restoring the native electrical microenvironment. This review focuses on the application of piezoelectric materials, conductive materials, and triboelectric materials in tendon repair. They produce ES in different ways. Piezoelectric materials generate charges through deformation within the crystal under the action of force, which in turn causes the arranged dipole moments to deform, resulting in a net electric field. Conductive materials can generate a large number of freely moving charged particles under the action of an electric field and thus can conduct current. When two different triboelectric materials come into contact, opposite charges are formed on each surface, resulting in contact electrification. The materials are inextricably linked to each other, so the scaffold is developed that may be a single or multiple ES scaffold. For example, the mixed application of conductive material poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) and piezoelectric material poly-L-lactic acid (PLLA), as well as the combined application of piezoelectric material polyvinylidene fluoride (PVDF) and triboelectric material nylon. More interestingly, PVDF is both a piezoelectric material and can generate charges under friction. Therefore, the development of high-performance cross-materials that can generate ES may be a better research direction in the future of tendon repair.
After nanoplastics (NPs) experience photoaging in an aquatic environment, they may enter blood circulation of organisms and interact with proteins, which significantly affect their cellular uptake and biological effects. In this study, polystyrene nanoplastics (PSNPs) and human serum albumin (HSA) were chosen as representative models of NPs and proteins, respectively. The photoaged PSNPs exhibited decreased particle size and increased surface oxidation, which not only promoted their binding with HSA but also led to preferential binding with the α-helix regions of HSA. Consequently, the α-helical content of the adsorbed HSA molecules on photoaged PSNPs decreased significantly, leading to a denaturation effect comparable to thermal treatment. Dissolved substances released from PSNPs had a negligible impact on HSA's conformation. The denatured HSA activated additional endocytic pathways, notably enhancing SR-A1-mediated endocytosis of mouse monocyte macrophages (RAW 264.7), which thus promoted the cellular uptake of the photoaged PSNPs compared with pristine ones. This study suggests that photoaging may greatly alter the interactions of NPs with proteins, thereby influencing cellular uptake mechanisms, and then alter their potential biodistribution and biological effects in vivo.
Peripheral nerve injury results in sensory and motor dysfunction, which is an enormous economic burden for patients and society. Complete recovery of peripheral nerve function after injury is complicated. Utilizing the electrophysiological properties of natural nerves for neuronal regulation and axon regeneration has attracted considerable interest. Electroactive biomaterials induce an active state of electrical stimulation (ES) at the site of peripheral nerve injury when incorporated into nerve guidance channels. Numerous studies have demonstrated that combining ES with electroactive biomaterials can enhance peripheral nerve repair. This review summarizes the regulation of signal pathways by ES and the functions of various electroactive biomaterials, including metals, carbon-based materials, conductive polymers, and piezoelectric materials. Recent advances and research of ES combined with electroactive biomaterials in peripheral nerve repair are reviewed, which may help to come up with more effective strategies to restore neural function after PNI.
Nerve guiding catheters (NGCs) are crucial for peripheral nerve repair, providing physical guidance and establishing a conducive microenvironment to nerve regeneration. In this study, we developed a bifunctional CS-HEC@PEDOT/SIM (CHPS) hydrogel-filled electrospun poly(L-lactide-co-caprolactone) (PLCL) conduit. The hydrogel matrix was fabricated using chitosan (CS) and hydroxyethyl cellulose (HEC) as the base materials, which exhibited excellent biocompatibility and degradability. Conductive poly(3,4-ethylenedioxythiophene) (PEDOT) was synthesized in situ within the matrix to establish stable electrostatic interactions with HEC, enhancing the electrical conductivity of the system. Additionally, the anti-inflammatory simvastatin (SIM) was uniformly dispersed throughout the hydrogel network through an optimized activation procedure. In vitro, the CHPS hydrogel exhibited promising electrical conductivity and sustained anti-inflammatory drug release. Furthermore, they supported neural cell proliferation and M2 macrophage polarization. In vivo, the CHPS hydrogel-filled conduits may create a favorable environment for electrical conductivity and inflammatory regulation, potentially promoting sciatic nerve regeneration in rats and facilitating partial recovery of motor function and nerve conduction. In conclusion, this approach may offer substantial potential for advancing nerve repair strategies and inspiring future clinical applications in the treatment of peripheral nerve injuries.
Background:Bone defect regeneration is a dynamic healing process that relies on the body's innate repair mechanisms, yet natural healing capacity remains limited. To address this challenge, advanced biomaterials combining bioactive inorganic components with biocompatible polymers have emerged as a promising strategy to enhance osteogenesis and angiogenesis. Methods:In this study, a novel three-dimensional composite scaffold material was successfully fabricated using a combined electrospinning-freeze drying technique. The scaffold incorporates flexible silicon dioxide-strontium oxide (SiO2-SrO) nanofibers as functional components, which are physically blended with a poly(lactic acid)/gelatin (PG) fibrous matrix to achieve composite construction. Result:The fabricated scaffolds exhibited an optimal well-ordered porous structure, excellent biocompatibility, and sustained release of therapeutic ions (Si4+ and Sr2+). Notably, they significantly upregulated osteogenic gene expression and enhanced angiogenic potential as demonstrated by improved tubulogenesis in HUVEC cultures. In vivo evaluation using a rat calvarial defect model confirmed their superior bone regeneration capability through simultaneous promotion of osteogenesis and angiogenesis. Conclusion:Leveraging the synergistic effects of SiO2-SrO nanofibers and PG polymers, this study presents a multifunctional scaffold capable of promoting bone regeneration through dual osteogenic and angiogenic stimulation. Our findings highlight the potential of this composite system not only for bone tissue engineering but also for broader biomedical applications.