An oxidized dextran-composite self-healing coated magnesium scaffold reduces apoptosis to induce bone regeneration.

Self-healing coatings have shown promise in controlling the degradation of scaffolds and addressing coating detachment issues. However, developing a self-healing coating for magnesium (Mg) possessing multiple biological functions in infectious environments remains a significant challenge. In this study, a self-healing coating was developed for magnesium scaffolds using oxidized dextran (OD), 3-aminopropyltriethoxysilane (APTES), and nano-hydroxyapatite (nHA) doped micro-arc oxidation (MHA), named OD-MHA/Mg. The results demonstrated that the OD-MHA coating effectively addresses coating detachment issues and controls the degradation of Mg in an infectious environment through self-healing mechanisms. Furthermore, the OD-MHA/Mg scaffold exhibits antibacterial, antioxidant, and anti-apoptotic properties, it also promotes bone repair by upregulating the expression of osteogenesis genes and proteins. The findings of this study indicate that the OD-MHA coated Mg scaffold possessing multiple biological functions presents a promising approach for addressing infectious bone defects. Additionally, the study showcases the potential of polysaccharides with multiple biological functions in facilitating tissue healing even in challenging environments.

The occurrence and development mechanisms of esophageal stricture: state of the art review.

BACKGROUND: Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease's etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention. METHODS: A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles. RESULTS: Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures. CONCLUSION: The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.

Axial assembly of AuNR for tumor theranostics via Zn2+-GSH chelation induced degradation of AuNR@ZIF-8 heterostructures.

Tumor microenvironment responsive photothermal ablation is a noninvasive and accurately targeted approach for cancer therapy. Herein, an intracellular directional assembly strategy for enhanced photothermal therapy (PTT) was realized by using ZIF-8 encapsulated Au nanorod (AuNR) heterostructure as the precursor of photothermal convertible material. The ZIF-8 shell selectively degraded in tumor cells upon the chelation between GSH and Zn2+, while the as-formed Zn(SG) connected the released AuNR in end-to-end fashion. The coating of ZIF-8 shell significantly improves the stability and targeting of AuNR, and the released Zn2+ shielded the GSH binding site on the lateral side of AuNR, increased the plasmonic coupling efficiency of AuNR assembly geometer. This design enabled atomic-economical, efficient and low-side effect targeted photothermal therapy through the effective integration of heterostructures.

Flexible Organic Photovoltaic-Powered Hydrogel Bioelectronic Dressing With Biomimetic Electrical Stimulation for Healing Infected Diabetic Wounds.

Electrical stimulation (ES) is proposed as a therapeutic solution for managing chronic wounds. However, its widespread clinical adoption is limited by the requirement of additional extracorporeal devices to power ES-based wound dressings. In this study, a novel sandwich-structured photovoltaic microcurrent hydrogel dressing (PMH dressing) is designed for treating diabetic wounds. This innovative dressing comprises flexible organic photovoltaic (OPV) cells, a flexible micro-electro-mechanical systems (MEMS) electrode, and a multifunctional hydrogel serving as an electrode-tissue interface. The PMH dressing is engineered to administer ES, mimicking the physiological injury current occurring naturally in wounds when exposed to light; thus, facilitating wound healing. In vitro experiments are performed to validate the PMH dressing's exceptional biocompatibility and robust antibacterial properties. In vivo experiments and proteomic analysis reveal that the proposed PMH dressing significantly accelerates the healing of infected diabetic wounds by enhancing extracellular matrix regeneration, eliminating bacteria, regulating inflammatory responses, and modulating vascular functions. Therefore, the PMH dressing is a potent, versatile, and effective solution for diabetic wound care, paving the way for advancements in wireless ES wound dressings.

Nanostructured ionic hydrogel with integrated conductivity, stretchability and thermal responsiveness for a high-performance strain and temperature sensor.

Ionic conductive hydrogels are promising candidates for fabricating wearable sensors for human motion detection and disease diagnosis, and electronic skin. However, most of the existing ionic conductive hydrogel-based sensors primarily respond to a single-strain stimulus. Only a few ionic conductive hydrogels can respond to multiple physiological signals. Although some studies have explored multi-stimulus sensors, such as those detecting strain and temperature, the ability to identify the type of stimulus remains a challenge, which limits their applications. Herein, a multi-responsive nanostructured ionic conductive hydrogel was successfully developed by crosslinking the thermally sensitive poly(N-isopropylacrylamide-co-ionic liquid) conductive nanogel (PNI NG) with a poly(sulfobetaine methacrylate-co-ionic liquid) (PSI) network. The resultant hydrogel (PNI NG@PSI) was endowed with good mechanical stretchability (300%), resilience and fatigue resistance, and excellent conductivity (2.4 S m-1). Furthermore, the hydrogel exhibited a sensitive and stable electrical signal response and has a potential application in human motion detection. Moreover, the introduction of a nanostructured thermally responsive PNIPAAm network also endowed it with a sensitive and unique thermal-sensing ability to timely and accurately record temperature changes in the range of 30-45 °C, holding promise for application as a wearable temperature sensor to detect fever or inflammation in the human body. In particular, as a dual strain-temperature sensor, the hydrogel demonstrated an excellent capability of distinguishing the type of stimulus from superposed strain-temperature stimuli via electrical signals. Therefore, the implementation of the proposed hydrogel in wearable multi-signal sensors provides a new strategy for different applications, such as health monitoring and human-machine interactions.

The osteogenesis and the biologic mechanism of thermo-responsive injectable hydrogel containing carboxymethyl chitosan/sodium alginate nanoparticles towards promoting osteal wound healing.

With the development of minimally invasive orthopedics, injectable materials for bone repair are attracted more attention, especially for those wound with a small external mouth and sizeable internal cavity. In this work, the hydrogel with features of thermo-responsiveness, degradability and injectability was designed and fabricated. The hydrogel, named as FHCS, is composed of Pluronic F-127 (F127) loaded with carboxymethyl chitosan/sodium alginate nanoparticles (nCS) and nanohydroxyapatite (nHA). The hydrogel FHCS was non-toxic and good hemocompatible. It can enhance the ALP activity and extracellular matrix calcification of MC3T3-E1 due to the chitosan-based nanoparticle components (nCS). Moreover, FHCS-5 (containing 5 mg/mL nCS) showed relative high expression of osteogenic genes and protein markers. Osteal regeneration was observed treated by FHCS-5 hydrogel in a critical-size rat calvarial bone defect model. CT scanning showed that the whole defect was basically covered by new bone after FHCS-5 hydrogel. The results of H&E staining and Masson's trichrome staining on histological sections further confirmed that FHCS-5 hydrogel promoted new osteal formation and maturation, which up regulated the osteogenic related genes and proteins of ALP, OCN, OPN through BMP/Smad signaling pathway. Hence, this study suggests that FHCS-5 hydrogels have a promising application for non-loading bone regeneration.

[Finite element analysis of optimal selection of cannulated threaded screw for the prevention of femoral neck shortening after internal fixation for femoral neck fracture].

OBJECTIVE: To propose the an optimal screw placement scheme to prevent femoral neck shortening, finite element analysis was used to evaluate the biomechanical outcome of different numbers formed by full threaded screws at different positions in the treatment of femoral neck fractures of Pauwels type Ⅱ. METHODS: Recruited for this study was a 55-year-old female volunteer with a weight of 70 kg and a height of 165 cm. CT scan data of her right femur was collected. The models of femoral of Pauwels typeⅡ and fully threaded screw(FTS) and partially threaded screw(PTS) were constructed in three-dimensional modeling software. All these screw placement schemes were divided into eight groups simulated the inverted triangular configuration:three PTSs, an anterosuperior FTS and two PTSs, a posterosuperior FTS and two PTSs, an inferior FTS and two PTSs, an anterosuperior PTS and two FTSs, a posterosuperior PTS and two FTSs, an inferior PTS and two FTSs and three FTSs. All fracture internal fixation models were processed in finite element analysis software. Parameters of postoperative femoral neck length, displacement distribution and peak displacement of screws and VonMises stress distribution and peak stress of screws, the proximal femur and fracture section were collected. RESULTS: The maximum VonMises stress of screws was 239.71, 213.44, 199.37, 230.82, 201.63, 215.72, 185.65 and 192.64 MPa, respectively, which was concentrated in the inferior screw near the fracture line. The maximum Von Mises stress of the proximal femur was 269.48, 241.62, 249.43, 269.69, 271.60, 346.64, 236.97 and 439.62 MPa, respectively, which was concentrated in the inferior medial area of subtrochanteric femur. The maximum Von Mises stress of fracture section was 149.12, 143.04, 140.47, 139.63, 139.81, 130.07, 117.77 and 57.89 MPa, respectively, which was concentrated around the partially threaded screw channel instead of the fully threaded screw channel. The maximum displacement of screws was 5.52, 5.43, 5.32, 5.17, 5.05, 5.13, 5.28 and 5.04 mm, respectively, which was along the axis of the femoral neck, and the displacement distribution was concentrated on the tip of the screw. The length of postoperative femoral neck length was 74.69, 74.72, 74.70, 74.70, 74.72, 74.70, 74.72 and 74.74 mm, respectively. CONCLUSION: The placement of one anterosuperior partially threaded screw and two fully threaded screws with an inverted triangular distribution can not only meet the sliding compression effect to promote femoral neck healing and ensure the stability of the proximal femur, but also reduce the degree of postoperative femoral neck shortening and reduce the incidence of hip joint dysfunction. This study provides a new optimal screw placement solution for the treatment of femoral neck fractures.

A Polyaniline Nanoparticles Crosslinked Hydrogel with Excellent Photothermal Antibacterial and Mechanical Properties for Wound Dressing.

Antibacterial hydrogel wound dressing is highly desirable in wound healing and infection control. However, the development of antibacterial hydrogels with controllable antibacterial properties and adequate mechanical properties without bacterial resistance and potential toxicity remains a challenge. Herein, a double bonds-ended polyaniline nanoparticle (Me-PANI NP) is synthesized, which can convert light energy into heat upon near-infrared (NIR) irradiation, and it is used as a novel photothermal antibacterial agent. The obtained bonds-ended Me-PANI NPs are subsequently involved in polyacrylamide (PAM) polymerization and served as chemical crosslinking points to form the Me-PANI NPs@PAM hydrogel, endowing the hydrogel with controllable photothermal antibacterial abilities upon NIR irradiation without time and space limit. Importantly, due to the energy dissipation of Me-PANI NPs under stretch, the Me-PANI NPs@PAM hydrogel achieves a maximum stretching ratio of 400% mechanical flexibility. The developed hydrogel can be potentially applied as a novel wound dressing to realize controllable treatment of bacterial infections and accelerate skin wound healing.

Gelatin-grafted tubular asymmetric scaffolds promote ureteral regeneration via activation of the integrin/Erk signaling pathway.

Introduction: The repair of a diseased ureter is an urgent clinical issue that needs to be solved. A tissue-engineered scaffold for ureteral replacement is currently insufficient due to its incompetent bioactivity, especially in long-segment abnormalities. The primary reason is the failure of urothelialization on scaffolds. Methods: In this work, we investigated the ability of gelatin-grafted tubular scaffold in ureteral repairment and its related biological mechanism. We designed various porous asymmetric poly (L-lactic acid) (PLLA)/poly (L-lactide-co-e-caprolactone) (PLCL) tubes with a thermally induced phase separation (TIPS) method via a change in the ratio of solvents (named PP). To regulate the phenotype of urothelial cells and ureteral reconstruction, gelatin was grafted onto the tubular scaffold using ammonolysis and glutaraldehyde crosslinking (named PP-gel). The in vitro and in vivo experiments were performed to test the biological function and the mechanism of the scaffolds. Results and Discussion: The hydrophilicity of the scaffold significantly increased after gelatin grafting, which promoted the adhesion and proliferation of urothelial cells. Through subcutaneous implantation in rats, PP-gel scaffolds demonstrated good biocompatibility. The in vivo replacement showed that PP-gel could improve urothelium regeneration and maintain renal function after the ureter was replaced with an ∼4 cm-long PP-gel tube using New Zealand rabbits as the experimental animals. The related biologic mechanism of ureteral reconstruction was detected in detail. The gelatin-grafted scaffold upgraded the integrin α6/ß4 on the urothelial cell membrane, which phosphorylates the focal adhesion kinase (FAK) and enhances urothelialization via the MAPK/Erk signaling pathway. Conclusion: All these results confirmed that the PP46-gel scaffold is a promising candidate for the constitution of an engineered ureter and to repair long-segment ureteral defects.

lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway.

BACKGROUND: We aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differentiation and angiogenesis in the development of osteoporosis. METHODS: The differential gene or proteins expressions were measured by qPCR or western blot assays, respectively. The targeted relationships among molecular were confirmed through luciferase reporter, RIP and ChIP assays, respectively. Alkaline phosphatase (ALP), alizarin red S (ARS) and TRAP staining were performed to measure the osteoblast/osteoclast differentiation of BMSCs. The viability, migration and angiogenesis in BM-EPCs were validated by CCK-8, clone formation, transwell and tube formation assays, respectively. Western blot and immunofluorescence detected the cytosolic/nuclear localization of ß-catenin. Ovariectomized (OVX) mice were established to confirm the findings in vitro. RESULTS: SNHG1 was enhanced and miR-181c-5p was decreased in serum and femoral tissue from OVX mice. SNHG1 directly inhibited miR-181c-5p to activate Wnt3a/ß-catenin signaling by upregulating SFRP1. In addition, knockdown of SNHG1 promoted the osteogenic differentiation of BMSCs by increasing miR-181c-5p. In contrast, SNHG1 overexpression advanced the osteoclast differentiation of BMSCs and inhibited the angiogenesis of BM-EPCs, whereas these effects were all reversed by miR-181c-5p overexpression. In vivo experiments indicated that SNHG1 silencing alleviated osteoporosis through stimulating osteoblastogenesis and inhibiting osteoclastogenesis by modulating miR-181c-5p. Importantly, SNHG1 could be induced by SP1 in BMSCs. CONCLUSIONS: Collectively, SP1-induced SNHG1 modulated SFRP1/Wnt/ß-catenin signaling pathway via sponging miR-181c-5p, thereby inhibiting osteoblast differentiation and angiogenesis while promoting osteoclast formation. Further, SNHG1 silence might provide a potential treatment for osteoporosis.

The biomechanical effect on the adjacent L4/L5 segment of S1 superior facet arthroplasty: a finite element analysis for the male spine.

BACKGROUND: The superior facet arthroplasty is important for intervertebral foramen microscopy. To our knowledge, there is no study about the postoperative biomechanics of adjacent L4/L5 segments after different methods of S1 superior facet arthroplasty. To evaluate the effect of S1 superior facet arthroplasty on lumbar range of motion and disc stress of adjacent segment (L4/L5) under the intervertebral foraminoplasty. METHODS: Eight finite element models (FEMs) of lumbosacral vertebrae (L4/S) had been established and validated. The S1 superior facet arthroplasty was simulated with different methods. Then, the models were imported into Nastran software after optimization; 500 N preload was imposed on the L4 superior endplate, and 10 N⋅m was given to simulate flexion, extension, lateral flexion and rotation. The range of motion (ROM) and intervertebral disc stress of the L4-L5 spine were recorded. RESULTS: The ROM and disc stress of L4/L5 increased with the increasing of the proportions of S1 superior facet arthroplasty. Compared with the normal model, the ROM of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 2/5 from the apex to the base. The disc stress of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 1/5 from the apex to the base. CONCLUSION: In this study, the ROM and disc stress of L4/L5 were affected by the unilateral S1 superior facet arthroplasty. It is suggested that the forming range from the ventral to the dorsal should be less than 3/5 of the S1 upper facet joint. It is not recommended to form from apex to base. LEVEL OF EVIDENCE: Level IV.

The biomechanical effects of graded upper articular process arthroplasty on lumbar spine: A finite element study.

BACKGROUND: Superior articular process arthroplasty is important for intervertebral foramen microscopy but may lead to spinal instability. Currently, there has been no relevant study in relation to the biomechanical analysis of superior articular process arthroplasty. Hence, this study is intended to verify biomechanical effects after unilateral S1 superior articular process arthroplasty. METHODS: Eight finite element (FE) models of lumbosacral vertebrae (L4-S) were constructed, and the superior articular process formation was simulated with the help of Geomagic studio. Then, the models were imported into Nastran software after optimization. Normal load and appropriate torque were applied to simulate forward flexion, back extension, lateral flexion and lateral rotation. In the end, changes of lumbar range of motion (ROM) and structural stress were compared with those of normal model. RESULTS: Compared with the normal model, formed from ventral to dorsal (Longitudinal), the larger motion of lumbar spine and the greater larger stress of articular process showed statistical significance (P < 0.05) in most of directions when the forming range was greater than 3/5. Formed from the apex to the base (transverse), the larger motion of lumbar spine and the greater stress of articular process showed statistical significance (P < 0.05) in most of directions when the forming range was great than 1/5. CONCLUSION: When conducting unilateral S1 articular process arthroplasty from ventral to dorsal, the forming range is recommended to be less than 3/5 of the superior articular process. Notably, it is not advisable to form from the apex to the base.