Abstract
Invasive electrical stimulation (iES) is prone to cause neural stimulus-inertia owing to its excessive accumulation of exogenous charges, thereby resulting in many side effects and even ...failure of nerve regeneration and functional recovery. Here, a wearable neural iES system is well designed and built for bionic and long-lasting neural modulation. It can automatically yield biomimetic pulsed electrical signals under the driven of respiratory motion. These electrical signals are full of unique physiological synchronization can give biofeedback to respiratory behaviors, self-adjusting with different physiological states of the living body, and thus realizing a dynamic and biological self-matched modulation of voltage-gated calcium channels on the cell membrane. Abundant cellular and animal experimental evidence confirm an effective elimination of neural stimulus-inertia by these bioelectrical signals. An unprecedented nerve regeneration and motor functional reconstruction are achieved in long-segmental peripheral nerve defects, which is equal to the gold standard of nerve repair -- autograft. The wearable neural iES system provides an advanced platform to overcome the common neural stimulus-inertia and gives a broad avenue for personalized iES therapy of nerve injury and neurodegenerative diseases.
In clinical settings the wound-dressing was required easy to use and can match the wound area immediately, at the same time they need to have the properties of hemostats, anti-inflammation and ...promoting wound healing. To get an ideal wound dressing, we developed a type of gel-like wound adhesive patch from spraying double-network hydrogel, which own the properties of self-antibacterial and can promote wound healing. By spraying, the gel-like wound adhesive patch can match the wound area immediately and form a gel-film in 10 s. Sodium carboxymethyl cellulose as pH sensitive materials accelerated the speed to form the gel-film and enhanced ductility of the wound adhesive patch. In vitro experiments show that, this gel-like wound adhesive patch can promote cell proliferation and reduce cell apoptosis. In vivo studies show that, compared with commercialized wound dressings in clinic using, the spraying gel-like wound adhesive patch from our work has a better effect on wound healing. In conclusion, the spraying gel-like wound patch in our work is easy to use and can form a gel-film match on wound area in a short time, also it has the properties of hemostats, anti-inflammation and promoting wound healing. Its feasibility for mass production shows a good potential for commercial use.
Display omitted We developed a type of gel-like wound adhesive patch from spraying double-network hydrogel, which own the properties of self-antibacterial and can promote wound healing. By spraying, the gel-like wound adhesive patch can match the wound area immediately and form a gel-film in 10 s.
Ankylosing Spondylitis (AS) is a chronic inflammatory disorder which can lead to considerable pain and disability. Mendelian randomization (MR) has been extensively applied for repurposing licensed ...drugs and uncovering new therapeutic targets. Our objective is to pinpoint innovative therapeutic protein targets for AS and assess the potential adverse effects of druggable proteins.
We conducted a comprehensive proteome-wide MR study to assess the causal relationships between plasma proteins and the risk of AS. The plasma proteins were sourced from the UK Biobank Pharma Proteomics Project (UKB-PPP) database, encompassing GWAS data for 2,940 plasma proteins. Additionally, GWAS data for AS were extracted from the R9 version of the Finnish database, including 2,860 patients and 270,964 controls. The colocalization analysis was executed to identify shared causal variants between plasma proteins and AS. Finally, we examined the potential adverse effects of druggable proteins for AS therapy by conducting a phenome-wide association study (PheWAS) utilizing the extensive Finnish database in version R9, encompassing 2,272 phenotypes categorized into 46 groups.
The findings revealed a positive genetic association between the predicted plasma levels of six proteins and an elevated risk of AS, while two proteins exhibited an inverse association with AS risk (
< 0.05). Among these eight plasma proteins, colocalization analysis identified AIF1, TNF, FKBPL, AGER, ALDH5A1, and ACOT13 as shared variation with AS(PPH3+PPH4>0.8), suggesting that they represent potential direct targets for AS intervention. Further phenotype-wide association studies have shown some potential side effects of these six targets (
< 0.05).
Our investigation examined the causal connections between six plasma proteins and AS, providing a comprehensive understanding of potential therapeutic targets.
•MSC-Exos play pivotal roles in Ferroptosis of macrophages in osteoarthritis.•MSC-Exos rescuedcartilageinjury in osteoarthritis through Ferroptosis by GOT1/CCR2/Nrf2/HO-1 signaling pathway.•MSC-Exos ...may be a novel treatment strategy for osteoarthritis or other orthopedic diseases in further investigation.
Osteoarthritis is a prevalent joint disease that significantly affects the daily life of the elderly and is one of the primary causes of disability in this population. This study aims to evaluate the potential pro-inflammatory effects and molecular mechanism of Mesenchymal stem cells-derived exosomes (MSC-Exos) in Osteoarthritis. Bilateral ovariectomy was carried out to induce osteoporosis under anesthesia for the mice. MC3T3-E1 cells were induced for 14 days.HE staining, Safranin O staining and Biomechanical parameter analysis were used in this experiment. MSC-Exos improved osteoarthritis in a mouse model by reducing inflammation levels, preventing ferroptosis, and inducing expression of GOT1/CCR2 to regulate ferroptosis. MSC-Exos also promoted cell growth and osteogenic differentiation of bone cells in an in vitro model. Inhibition of GOT1 reduced the effects of MSC-Exos on cell growth and osteogenic differentiation in an osteoarthritis model. MSC-Exos induce Nrf2/HO-1 expression through the GOT1/CCR2 signaling pathway, resulting in the reduction of Ferroptosis. However, inhibition of Nrf2 reduces the effectiveness of MSC-Exos in treating Osteoarthritis.The results of this study suggest that the GOT1/CCR2/Nrf2/HO-1 signaling pathway plays a crucial role in MSC-Exos-mediated reduction of Ferroptosis in macrophages during Osteoarthritis. These findings may provide a potential therapeutic approach for Osteoarthritis and other orthopedic conditions.
The long‐segment peripheral nerve injury (PNI) represents a global medical challenge, leading to incomplete nerve tissue recovery and unsatisfactory functional reconstruction. However, the current ...electrical stimulation (ES) apparatuses fail perfect nerve repair due to their inability of the variable synchronous self‐regulated function with physiological states. It is urgent to develop an implantable ES platform with physiologically adaptive function to provide instantaneous and nerve‐preferred ES. Here, a physiologically self‐regulated electrical signal is generated by integrating a novel tribo/piezoelectric hybrid nanogenerator with a nanoporous nerve guide conduit to construct a fully implantable neural electrical stimulation (FI‐NES) system. The optimal neural ES parameters completely originate from the body itself and are highly self‐responsive to different physiological states. The morphological evaluation, representative protein expression level, and functional reconstruction of the regenerated nerves are conducted to assess the PNI recovery process. Evidence shows that the recovery effect of 15 mm length nerve defects under the guidance of the FI‐NES system is significantly close to the autograft. The designed FI‐NES system provides an effective method for long‐term accelerating the recovery of PNI in vivo and is also appropriate for other tissue injury or neurodegenerative diseases.
A physiologically self‐regulated, fully implantable, battery‐free neural electrical stimulation system is successfully constructed to produce physiologically electrical signals for the acceleration of regeneration and functional recovery of peripheral nerve injury.
The current surgical techniques for repairing Ellman Ⅲ partial articular supraspinatus tendon avulsion (PASTA) is mainly tear completion followed by repair and in situ transtendon repair, and both ...techniques have been proven to have good clinical effects. In situ transtendon repair is more widely used because of its high performance in preserving the integrity of the bursal side supraspinatus tendon. However, there is still some scope for improvement. Our purpose was to compare the clinical outcomes of the all-inside repair technique and in situ transtendon repair for Ellman III PASTA.
A retrospective comparative study was conducted on 56 patients who suffered from Ellman Ⅲ PASTA and underwent rotator cuff repair; 28 patients were treated with the all-inside technique (group A), and 28 patients were treated with the transtendinous technique (group B). All patients were followed up for at least 2 years. The visual analog scale (VAS), Constant, and American Shoulder and Elbow Surgeons (ASES) scores were used to evaluate the patient’s shoulder joint function before surgery, 1 month and 3 months after surgery, and at the last time of follow-up.
Group A showed superiority in pain and functional improvement 1 month after the operation: the VAS score, 2.8 ± 0.3 in group A vs. 4.7 ± 0.4 in group B (P = .042); Constant score, 73 ± 5 in group A vs. 60 ± 6 in group B (P = .038); and ASES score, 75 ± 5 in group A vs. 58 ± 7 in group B (P = .043), whereas there was no statistical difference in group B. However, 3 months after surgery and at the last follow-up, the VAS, Constant, and ASES scores in both groups were significantly improved (P < .01), and there was no significant statistical difference between the groups (P > .05). Magnetic resonance imaging showed that the repaired rotator cuff tendon-bone healed well; at the last follow-up, all patients were in good function, the pain was completely relieved, and no revision was performed in both groups.
Arthroscopic repair of Ellman Ⅲ PASTA provided satisfactory functional improvements and pain relief regardless of the all-inside and in situ transtendon repair techniques. However, the all-inside repair technique is more beneficial due to its dual function in preserving the intact bursa and avoidance of uneven tension of the articular side, which is advantageous to early postoperative rehabilitation.
•We found in rat models that EVs derived from damaged articular cartilage chondrocytes might participate in and play an important role in the progression of OA. The delivered LncRNA LOC102546541 ...would damage cartilage degrading the ECM.•We have constructed siRNA (targeting this lncRNA) loaded engineered EVs as a novel strategy for the treatment of OA, and have found some positive results.•In the future, the highly homologous human gene of LOC102546541 can not only be used as a marker for diagnosing ACD/OA, but also as a new target for therapy.
Articular cartilage defects (ACD) are injuries with a diameter greater than 3 mm, resulting from wear and tear on joints. When the diameter of the defect exceeds 6 mm, it can further damage the surrounding joint cartilage, causing osteoarthritis (OA). Try to explain why OA is an irreversible disease, we hypothesize that damaged articular chondrocytes (DAC) may have reduced capacities to repair cartilage because its extracellular vesicle (EVs) that might directly contribute to OA formation.
In this study, DAC-EVs and AC-EVs were isolated using ultracentrifugation. Next-generation sequencing was employed to screen for a pathogenic long non-coding RNA (lncRNA). After verifying its function in vitro, the corresponding small interfering RNA (siRNA) was constructed and loaded into extracellular vesicles, which were then injected into the knee joint cavities of rats.
The results revealed that DAC-EVs packaged lncRNA LOC102546541 acts as a competitive endogenous RNA (ceRNA) of MMP13, down-regulating miR-632. Consequently, the function of MMP13 in degrading the extracellular matrix is enhanced, promoting the development of osteoarthritis.
This study uncovered a novel mode of OA pathogenesis using rat models, which DAC deliver pathogenic LOC102546541 packaged EVs to normal articular chondrocytes, amplifying the degradation of the extracellular matrix. Nonetheless, the functions of highly homologous human gene of LOC102546541 need to be verified in the future.
Electrical stimulation (ES) is widely used in physiological and medical sciences, while its application to treat inflammatory skin diseases (ISDs) remains a challenge owing to their natural ...pathological cuticle barrier and lack of an effective combination with chemotherapy to achieve specific immunomodulation. Here, a wearable, battery‐free, multi‐component drug‐loaded electronic microneedle (mD‐eMN) system is developed by integrating remodeled metal microneedles loaded with multi‐component chemical drugs and flexible triboelectric nanogenerators (TENGs). The system can rapidly release drugs into the site of ISDs and then realize an efficient penetration into cell body and specific immunomodulation under the synergism of pulsed electrons originating from the TENG. Also, the pulsed electrons can promote skin tissue homeostasis reconstruction to alleviate the inflammatory process of ISDs. Sufficient evidence shows that a significant skin inflammation regression of psoriasis (a typical ISDs model) is achieved using the mD‐eMN system compared to traditional ES or chemotherapy alone. This innovative wearable mD‐eMN system provides an effective flexible electronic and chemical drug joint technological platform for the treatment of ISDs, which is not only suitable for the treatment of psoriasis in this study but also maybe for other ISDs such as diabetic ulcers and skin tumors.
Electrical stimulation is widely used in physiological and medical sciences, but its application to treat inflammatory skin diseases (ISDs) remains a challenge. Here, a wearable, battery‐free, multi‐component drug‐loaded electronic microneedle system is developed. The system can rapidly release drugs into the site of ISDs and then realize specific immunomodulation under the synergism of pulsed electrons originating from the triboelectric nanogenerators.
Numerous patients experience articular cartilage defects (ACDs), which are characterized by progressive cartilage degradation and often lead to osteoarthritis (OA). Consequently, 44.7% of OA patients ...suffer from dyskinesia or disability. Current clinical drug treatments offer limited effectiveness in fully curing the disease. In this study, we propose a collaborative approach that combines physical and biological cues to promote cartilage regeneration. A biodegradable piezoelectric poly (l-lactic acid) (PLLA) nanofiber scaffold facilitates in situ, battery-free electrical stimulation under natural joint loading, while extracellular vesicles (EVs) serve as communication mediators between cells and promote cell proliferation, migration, and secretion of type II collagen. In this combined approach, EVs attached to PLLA are gradually released by localized piezoelectric electrical stimulation and taken up by chondrocytes. This process results in the organization of type II collagen along the PLLA fiber surface, ultimately forming cartilage lacunae that facilitate the residence of new chondrocytes. As an outcome, a significant round cartilage defect (diameter: 3 mm and depth: 1 mm) in the PLLA/EVs group (rat and knee) was rapidly restored within six weeks. In contrast, individual EVs and PLLA groups demonstrated considerably weaker cartilage regeneration capabilities. This research suggests that the synergistic effect of electromechanical stimulation and EVs-based biological cues is a crucial intervention method for treating OA.
