A bioenergetically-active ploy (glycerol sebacate)-based multiblock hydrogel improved diabetic wound healing through revitalizing mitochondrial metabolism.

Diabetic wounds impose significant burdens on patients' quality of life and healthcare resources due to impaired healing potential. Factors like hyperglycemia, oxidative stress, impaired angiogenesis and excessive inflammation contribute to the delayed healing trajectory. Mounting evidence indicates a close association between impaired mitochondrial function and diabetic complications, including chronic wounds. Mitochondria are critical for providing energy essential to wound healing processes. However, mitochondrial dysfunction exacerbates other pathological factors, creating detrimental cycles that hinder healing. This study conducted correlation analysis using clinical specimens, revealing a positive correlation between mitochondrial dysfunction and oxidative stress, inflammatory response and impaired angiogenesis in diabetic wounds. Restoring mitochondrial function becomes imperative for developing targeted therapies. Herein, we synthesized a biodegradable poly (glycerol sebacate)-based multiblock hydrogel, named poly (glycerol sebacate)-co-poly (ethylene glycol)-co-poly (propylene glycol) (PEPGS), which can be degraded in vivo to release glycerol, a crucial component in cellular metabolism, including mitochondrial respiration. We demonstrate the potential of PEPGS-based hydrogels to improve outcomes in diabetic wound healing by revitalizing mitochondrial metabolism. Furthermore, we investigate the underlying mechanism through proteomics analysis, unravelling the regulation of ATP and nicotinamide adenine dinucleotide metabolic processes, biosynthetic process and generation during mitochondrial metabolism. These findings highlight the therapeutic potential of PEPGS-based hydrogels as advanced wound dressings for diabetic wound healing.

CO2-Mediated Alkali-Neutralization Curdlan Hydrogels for Potential Wound Healing Application.

Physical hydrogels of natural polysaccharides are considered as ideal candidates for wound dressing due to their natural biological activity and no harmful cross-linking agents. However, it remains a challenge to fabricate such hydrogel dressings in a facile and low-cost way. Herein, we reported an easy and cost-effective method to construct CO2-mediated alkali-neutralization Curdlan (CR) hydrogels without using an external cross-linking agent. Two types of hydrogels (denoted as CR-NaOH and CR-Na3PO4, respectively) were fabricated by dissolving CR powders in a NaOH or Na3PO4 aqueous solution, followed by keeping the CR alkaline solutions in air. The obtained pure CR hydrogels possessed a tunable porous structure with walls containing different forms of nanofibrils. These hydrogels exhibited much higher gel strength by comparison with the gels prepared by conventional heating treatment. They were flexible, stretchable, twistable, and conformable to arbitrarily curved skins. Moreover, they exhibited ideal swellability, proper degradability, and water vapor transmission rate, and their physicochemical properties were closely related to CR concentration in the alkaline solution. These two hydrogels also supported the growth of L929 cells. Importantly, studies on wound healing revealed that both 3CR-NaOH and 3CR-Na3PO4 hydrogels were capable of accelerating the wound healing process through recruiting more macrophages/fibroblasts, inducing more collagen deposition and neovascularization (α-SMA and CD31) without carrying any exogenous bioactive components. In conclusion, the present work not only reported promising materials for application in wound therapy but also offered a facile and safe manufacturing procedure for generating pure CR physical hydrogels with better performance.

Compressive buttress compared with off-axial screw fixation for vertical femoral neck fractures in young adults: a prospective, randomized controlled trial.

BACKGROUND: To compare the clinical outcomes of compressive buttress screw (CBS) fixation, a novel screw fixation strategy, to off-axial screw fixation (off-axial partial threaded cannulated screw, OPTCS) for vertical femoral neck fractures (FNFs) in young adults. METHODS: A total of 146 adults younger than 55 years old with high-energy Pauwels type III FNFs were randomized to receive CBS fixation or OPTCS fixation. Primary outcomes were complication rates, including fixation failure, fracture nonunion, and avascular necrosis of the femoral head (ANFH) at 24 months after treatment. Fixation loosening, femoral neck shortening and varus collapse, patient function and quality of life using the Harris hip score (HHS), and EuroQol-5 dimensional-5 levels (EQ-5D-5L) questionnaire (including EQ-5D-5L and EQ-VAS) were assessed as secondary outcomes at 24 months. RESULTS: CBS and OPTCS fixation groups were similar with regard to demographics at baseline. At 24 months, patients in the CBS fixation cohort had a significantly lower rate of fixation failure (10.5% vs. 25.0%, p = 0.041) and fracture nonunion (1.8% vs. 18.3%, p = 0.003) compared with patients who received OPTCS fixation. There was no difference in rate of ANFH (7.0% vs. 11.7%, p = 0.389) between groups. Additionally, patients managed with CBS fixation showed significantly less fixation loosening (19.3% vs. 58.3%, p < 0.001), less severe femoral neck shortening and varus collapse (10.5% vs. 25.0%, p = 0.007), higher HHS (93 vs. 83, p = 0.001) and more excellent grade (68.4% vs. 36.7%, p = 0.008), higher EQ-5D-5L (0.814 vs, 0.581, p < 0.001) and EQ-VAS (85 vs. 80, p = 0.002). CONCLUSION: CBS screw fixation confers significantly lower complication rate in addition to higher functional and quality of life outcomes for young adults with high-energy FNF compared with OPTCS fixation. TRIAL REGISTRATION: This prospective, randomized controlled trial was approved by the institutional review board of our center, Ethics Committee of Shanghai sixth people's Hospital, and registered at www.chictr.org.cn (Approval Number: ChiCTR1900026283; Registered 29 September 2019-Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=43164 ).

Morphological characteristics of femoral neck fractures in young and middle-aged population: a retrospective descriptive study.

BACKGROUND: A understanding of morphological characteristics are important to femoral neck fractures (FNFs) resulting in high rates of complications in the young and middle-aged adults and the detailed data is lack in the literature. We aimed to report on the detailed morphological characteristics and the relationship between them in young and middle-aged adults with femoral neck fractures (FNFs). METHODS: The postoperative CT images of one hundred and fifty-two adults with FNFs were retrospectively reviewed. After image standardization, morphological characteristics including fracture orientation, cortex comminution, and intraosseous bone defects were measured and analyzed. Additionally, the distribution and correlation of these morphological features were analyzed using Pauwels classification, the right angle of the neck axis (VNA) classification, and the anteromedial oblique angle (AMA). RESULTS: Pauwels III fractures accounted for approximately half (55.2%) of the FNFs analyzed. Pauwels II and III could be detected in all four VNA types, and the distribution of the Pauwels types in VNA classification showed significant differences (χ2 = 106.363, p < 0.001). The VNA (9.0° ± 12.1) showed positive correlation with the neck-shaft angle (139.5° ± 6.3) and modified Pauwels angle (49.8° ± 10.6) (r = 0.441, r = 0.855, all p < 0.001). Cortical comminutions were commonly observed in the posterior (86.7%) and the inferior (80.7%). AMAs within the cases without posterior and inferior cortex comminutions were significantly larger than those with comminution (t = 2.594, 2.1196; p = 0.01, 0.036), but no difference could be detected after the AMA being divided into three groups (< 85°, 85°-95°, > 95°). The MPA, VNA and AMA of the group with an intraosseous defect were significantly different compared with those without (t = 2.847, 2.314, 2.268; p = 0.005, 0.022,0.025). The incidence of intraosseous defects within the groups with coronal and axial cortex comminutions were significantly higher than those within the groups without comminutions (χ2 = 34.87, 25.303; p < 0.001). CONCLUSIONS: The present study highlights the morphological diversity and complexity within FNFs in young and middle-aged adults, which allows for more accurate simulation of FNF patterns in the future biomechanical studies.

Effect of Fe on the Hydrogen Production Properties of Al-Bi-Sn Composite Powders.

Fe additives may play an important role in the preparation of aluminum-based hydrolysis hydrogen powder, with high hydrogen yield, low cost, and good oxidation resistance. Therefore, it is necessary to ascertain the effect of Fe on the hydrogen production performance of Al-Bi-Sn composite powders. According to the calculated vertical cross-section of the Al-10Bi-7Sn-(0~6)Fe (wt.%) quasi-binary system, Al-10Bi-7Sn-xFe (x = 0, 0.5, 1.5, 3) wt.% composite powders for hydrogen production were prepared by the gas-atomization method. The results showed that the Al-10Bi-7Sn-1.5Fe (wt.%) powder exhibited an extremely fast hydrogen generation rate at 50 °C, which reached 1105 mL·g-1 in 27 min in distilled water, 1086 mL·g-1 in 15 min in 0.1 mol·L-1 NaCl solution, and 1086 mL·g-1 in 15 min in 0.1 mol·L-1 CaCl2 solution. In addition, the antioxidant properties of these powders were also investigated. The results showed that the hydrogen production performance of the Al-10Bi-7Sn-1.5Fe (wt.%) powder could retain 91% of its hydrogen production activity, even though the powder was exposed to 25 °C and 60 RH% for 72 h. The addition of Fe not only promoted the hydrogen generation rate of the Al-Bi-Sn composite powders, but also improved their oxidation resistance. The Al-10Bi-7Sn-1.5Fe (wt.%) composite powder shows great potential for mobile hydrogen source scenarios with rapid hydrogen production.

Biomechanical evaluation of compression buttress screw and medial plate fixation for the treatment of vertical femoral neck fractures.

OBJECTIVE: To compare the biomechanical properties of compression buttress screw (CBS) fixation with three plate fixation methods for the treatment of vertical femoral neck fractures (FNFs). METHODS: A total of forty synthetic femoral models with simulated Pauwels type III fractures (angle of 70°) were equally assigned to one of four fixation groups: CBS fixation, anteromedial plate fixation (AMP), medial buttress plate fixation (MBP) and medial buttress plate fixation without proximal screw (MBPw). Within each group, half of the specimens were randomly assigned to two loading settings, an axial compression loading test and a hip-flexion torsion test. RESULTS: There were no significant differences in axial load to failure, axial stiffness, torsional strength, or torsional stiffness when comparing CBS with MBP (p>0.05). In the axial compression loading test, both CBS and MBP showed higher load to failure and axial stiffness than MBPw (p<0.05). In torsional testing, AMP exhibited superior torsional strength and torsional stiffness than both MBPw and MBP (all p<0.05) and a higher torsional strength than CBS fixation (p<0.05). There were no significant differences in torsional stiffness between the CBS and AMP fixation groups (p>0.05). CONCLUSION: The biomechanical parameters of CBS fixation are comparable to that of AMP and MBP, and demonstrate superior axial stiffness than MBPw fixation. Although the CBS method for surgical fixation of vertical FNF holds promise as a less invasive surgical technique than plate fixation with similar biomechanical assessments, further clinical evaluation is warranted.

Acellular fish skin enhances wound healing by promoting angiogenesis and collagen deposition.

Acellular matrix is a type of promising biomaterial for wound healing promotion. Although acellular bovine and porcine tissues have proven effective, religious restrictions and risks of disease transmission remain barriers to their clinical use. Acellular fish skin (AFS), given its similarity to human skin structure and without the aforementioned disadvantages, is thus seen as an attractive alternative. This study aims to fabricate AFS from the skin of black carp (Mylopharyngodon piceus), evaluate its physical and mechanical properties and assess its impact on wound healing. The results showed that AFS has a highly porous structure, along with high levels of hydrophilicity, water-absorption property and permeability. Furthermore, physical characterization showed the high tensile strength of AFS in dry and wet states, and high stitch tear resistance, indicating great potential in clinical applications. Cell Counting Kit-8 was used to test the viability of L929 cells when culturing in the extracts of AFS. Compared with the control group, there is no significant difference in optical density value when culturing in the extracts of AFS at days 1, 3 and 7 (*p> 0.05).In vivowound healing evaluation then highlighted its promotion of angiogenesis and collagen synthesis, its function in anti-inflammation and acceleration in wound healing. Therefore, this study suggests that AFS has potential as a promising alternative to mammal-derived or traditional wound dressing.

Epidermal growth factor/epidermal growth factor receptor moves into the osteoblasts' cell nuclei where it is involved to regulate STAT5's signaling.

Epidermal growth factor (EGF) has vital biological impacts on the osteoblasts. However, the knowledge on the cellular properties of EGF/EGFR (epidermal growth factor receptor) on osteoblasts is scanty. As such, we explored the EGF/EGFR's cell behavior in the osteoblast (MC3T3-E1 cell) using the indirect immunofluorescence assay, Western-blot, and fluorescence resonance energy transfer. Our findings revealed that EGF could internalize into the cytoplasm under EGFR mediation. Besides, the co-localization analysis demonstrated that caveolin played a critical role in EGFR's endocytosis. We also analyzed the cytoplasmic trafficking pathway of EGF/EGFR in MC3T3-E1 cell. The colocalization analysis showed that EGFR entered into Rab5, Rab4, and Rab9-positive endosomes. More importantly, we found that EGFR could move into the MC3T3-E1 cells' nuclei. Based on this, we investigated the EGFR's nuclear-localized functions, and the results suggested that nuclear-localized EGFR has important biological functions. This work lays a foundation for further study on EGF/EGFR's biological functions on the osteoblasts.

Effects of hypoxia environment on osteonecrosis of the femoral head in Sprague-Dawley rats.

INTRODUCTION: Osteonecrosis of the femoral head (ONFH) is a disease in which the blood supply of the femoral head is interrupted or damaged, resulting in joint dysfunction. Hypoxic environments increase the expression of EPO, VEGF, and HIF causes vascular proliferation and increases the blood supply. It also causes the organism to be in a state of hypercoagulability and increases thrombosis. Therefore, the purpose of this study was to explore the occurrence of ONFH after the use of glucocorticoids (GCs) under conditions of hypoxia tolerance for a long time. MATERIALS AND METHODS: Sprague-Dawley rats were fed in a hypobaric hypoxic chamber at an altitude of 4000 m, the whole blood viscosity, and plasma viscosity were determined to analyze the blood flow and hemagglutination. Western blotting, polymerase chain reaction, and immunohistochemistry were used to detect EPO, VEGF, CD31, and osteogenesis related proteins. Femoral head angiography was used to examine the local blood supply and micro-CT scanning was used to detect the structure of the bone trabecula. RESULTS: Under hypoxic environments, the expression of EPO and VEGF increased, which increased the local blood supply of the femoral head, but due to more severe thrombosis, the local blood supply of the femoral head decreased. CONCLUSIONS: Hypoxic environments can aggravate ONFH in SD rats; this aggravation may be related to the hypercoagulable state of the blood. We suggest that long-term hypoxia should be regarded as one of the risk factors of ONFH and we need to conduct a more extensive epidemiological investigation on the occurrence of ONFH in hypoxic populations.

Biomechanical Evaluation of the Modified Cannulated Screws Fixation of Unstable Femoral Neck Fracture with Comminuted Posteromedial Cortex.

PURPOSE: To verify the biomechanical importance with respect to the integrity of posteromedial cortex of femoral neck fracture (FNF) and demonstrate whether the modified fixation of cannulated screws (CSs) could increase the biomechanical strength. METHODS: A total of 24 left artificial femurs were randomly divided into three groups. The osteotomy was made in the center of the femoral neck at a 20° angle to the shaft axial. The posteromedial cortices of femoral neck were removed in groups B and C. In group A, 8 femurs with intact posteromedial cortex were fixed with three parallel partial thread screws (PTSs), forming a standard triangle. In group B, the femurs were stabilized with the same fixation of CSs like group A. In group C, two inferior PTSs were replaced by two fully thread screws (FTSs). RESULTS: The lower A-P and axial stiffness and load to failure along with higher axial displacement were found in group B compared with group A (p≤0.001 for all). Between groups B and C, the modified fixation of CSs increased A-P and axial stiffness and load to failure and reduced the axial displacement (p≤0.001 for all). CONCLUSIONS: We verified that the comminuted posteromedial cortex affected the biomechanical strength adversely and resulted in higher displacement. The modified fixation of CSs characterized by two inferior FTSs could improve the biomechanical performance and buttress the femoral head fragment better.