Ropivacaine microsphere-loaded electroconductive nerve dressings for long-acting analgesia and functional recovery following diabetic peripheral nerve injury.

In recent years, electroconductive hydrogels (ECHs) have shown great potential in promoting nerve regeneration and motor function recovery following diabetic peripheral nerve injury (PNI), attributed to their similar electrical and mechanical characteristics to innate nervous tissue. It is well-established that PNI causes motor deficits and pain, especially in diabetics. Current evidence suggests that ropivacaine (ROP) encapsulated in poly lactic-co-glycolic acid (PLGA) microspheres (MSs) yield a sustained analgesic effect. In this study, an ECH electroconductive network loaded with MS/ROP (ECH-MS/ROP) was designed as a promising therapeutic approach for diabetic PNI to exert lasting analgesia and functional recovery. This dual delivery system allowed ROP's slow and sequential release, achieving sustained analgesia as demonstrated by our in vivo experiments. Meanwhile, this system was designed like a lamellar dressing, with desirable adhesive and self-curling properties, convenient for treating injured nerve tissues via automatically wrapping tube-like structures, facilitating the process of implantation. Our in vitro assays verified that ECH-MS/ROP was able to enhance the adhesion and motility of Schwann cells. Besides, both in vitro and in vivo studies substantiated that ECH-MS/ROP stimulated myelinated axon regeneration through the MEK/ERK signaling pathway, thereby improving muscular denervation atrophy and facilitating functional recovery. Therefore, this study suggests that the ECH-MS/ROP dressing provides a promising strategy for treating diabetic PNI to facilitate nerve regeneration, functional recovery and pain relief.

In situ sprayed hydrogels containing resiquimod-loaded liposomes reduce chronic osteomyelitis recurrence by intracellular bacteria clearance.

At present, surgical debridement and systematic administration of antibiotics represent the mainstay of treatment for chronic osteomyelitis. However, it is now understood that Staphylococcus aureus (S. aureus) can survive within excessively polarized M2 macrophages and evade antibiotics, accounting for the high recurrence of chronic osteomyelitis. Effective treatments for intracellular infection have rarely been reported. Herein, we designed an in situ sprayed liposomes hydrogels spray with macrophage-targeted effects and the ability to reverse polarization and eradicate intracellular bacteria to reduce the recurrence of osteomyelitis. Resiquimod (R848)-loaded and phosphatidylserine (PS)-coating nanoliposomes were introduced into fibrinogen and thrombin to form the PSL-R848@Fibrin spray. Characterization and phagocytosis experiments were performed to confirm the successful preparation of the PSL-R848@Fibrin spray. Meanwhile, in vitro cell experiments validated its ability to eliminate intracellular S. aureus by reprogramming macrophages from the M2 to the M1 phenotype. Additionally, we established a chronic osteomyelitis rat model to simulate the treatment and recurrence process. Histological analysis demonstrated a significant increase in M1 macrophages and the elimination of intracellular bacteria. Imaging revealed a significant decrease in osteomyelitis recurrence. Overall, the liposome hydrogels could target macrophages to promote antibacterial properties against intracellular infection and reduce the recurrence of chronic osteomyelitis, providing the foothold for improving the outcomes of this patient population. STATEMENT OF SIGNIFICANCE: Chronic osteomyelitis remains a high recurrence although undergoing traditional treatment of debridement and antibiotics. S. aureus can survive within the excessively polarized M2 macrophages to evade the effects of antibiotics. However, few studies have sought to investigate effective intracellular bacteria eradication. Herein, we designed a macrophage-targeted R848-containing liposomes fibrin hydrogels spray (PSL-R848@Fibrin) that can reprogram polarization of macrophages and eradicate intracellular bacteria for osteomyelitis treatment. With great properties of rapid gelation, strong adhesion, high flexibility and fit-to-shape capacity, the facile-operated immunotherapeutic in-situ-spray fibrin hydrogels exhibited huge promise of reversing polarization and fighting intracellular infections. Importantly, we revealed a hitherto undocumented treatment strategy for reducing the recurrence of chronic osteomyelitis and potentially improving the prognosis of chronic osteomyelitis patients.

Investigation on physicochemical properties, sensory quality and storage stability of mayonnaise prepared from lactic acid fermented egg yolk.

In this research, the physicochemical properties, sensory quality, and storage stability of mayonnaise prepared from egg yolk fermented for different times (0, 3, 6, and 9 h) have been investigated. Compared with control mayonnaise (3.50 µm and 92.88%), mayonnaise prepared from fermented egg yolk possessed significantly lower particle size (3.32-3.41 µm) and higher emulsion stability (97.26-98.72%). Meanwhile, texture, color, and gas chromatography-mass spectrometry (GC-MS) analysis revealed that the fermented egg yolk significantly enhanced the firmness, consistency and cohesiveness, lightness and redness, and flavor profile of mayonnaise. Sensory evaluation showed that mayonnaise with 3 h-fermented egg yolk exhibited the highest sensory scores. And the microscopic and appearance characteristics revealed that fermented egg yolk endowed mayonnaise with a more stable appearance after 30 days of storage. These results indicated that lactic acid fermentation of egg yolk is a feasible way to improve consumer acceptability and shelf life of mayonnaise.

Exosomes-loaded electroconductive nerve dressing for nerve regeneration and pain relief against diabetic peripheral nerve injury.

Over the years, electroconductive hydrogels (ECHs) have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury (PNI) with diabetes, given their favorable mechanical and electrical properties identical to endogenous nerve tissue. Nevertheless, PNI causes the loss of locomotor function and inflammatory pain, especially in diabetic patients. It has been established that bone marrow stem cells-derived exosomes (BMSCs-Exos) have analgesic, anti-inflammatory and tissue regeneration properties. Herein, we designed an ECH loaded with BMSCs-Exos (ECH-Exos) electroconductive nerve dressing to treat diabetic PNI to achieve functional recovery and pain relief. Given its potent adhesive and self-healing properties, this laminar dressing is convenient for the treatment of damaged nerve fibers by automatically wrapping around them to form a size-matched tube-like structure, avoiding the cumbersome implantation process. Our in vitro studies showed that ECH-Exos could facilitate the attachment and migration of Schwann cells. Meanwhile, Exos in this system could modulate M2 macrophage polarization via the NF-κB pathway, thereby attenuating inflammatory pain in diabetic PNI. Additionally, ECH-Exos enhanced myelinated axonal regeneration via the MEK/ERK pathway in vitro and in vivo, consequently ameliorating muscle denervation atrophy and further promoting functional restoration. Our findings suggest that the ECH-Exos system has huge prospects for nerve regeneration, functional restoration and pain relief in patients with diabetic PNI.

Triple-functional bone adhesive with enhanced internal fixation, bacteriostasis and osteoinductive properties for open fracture repair.

At present, effective fixation and anti-infection implant materials represent the mainstay for the treatment of open fractures. However, external fixation can cause nail tract infections and is ineffective for fixing small fracture fragments. Moreover, closed reduction and internal fixation during the early stage of injury can lead to potential bone infection, conducive to bone nonunion and delayed healing. Herein, we designed a bone adhesive with anti-infection, osteogenic and bone adhesion fixation properties to promote reduction and fixation of open fractures and subsequent soft tissue repair. It was prepared by the reaction of gelatin (Gel) and oxidized starch (OS) with vancomycin (VAN)-loaded mesoporous bioactive glass nanoparticles (MBGNs) covalently cross-linked with Schiff bases. Characterization and adhesion experiments were conducted to validate the successful preparation of the Gel-OS/VAN@MBGNs (GOVM-gel) adhesive. Meanwhile, in vitro cell experiments demonstrated its good antibacterial effects with the ability to stimulate bone marrow mesenchymal stem cell (BMSCs) proliferation, upregulate the expression of alkaline phosphatase (ALP) and osteogenic proteins (RunX2 and OPN) and enhance the deposition of calcium nodules. Additionally, we established a rat skull fracture model and a subcutaneous infection model. The histological analysis showed that bone adhesive enhanced osteogenesis, and in vivo experiments demonstrated that the number of inflammatory cells and bacteria was significantly reduced. Overall, the adhesive could promote early reduction of fractures and antibacterial and osteogenic effects, providing the foothold for treatment of this patient population.

Phosvitin-wheat gluten complex catalyzed by transglutaminase in the presence of Na2SO3: Formation, cross-link behavior and emulsifying properties.

Phosvitin (PSV) is considered as a good emulsifier, although it has a low proportion of hydrophobic regions and steric hindrance. Wheat gluten (WG) possesses excellent hydrophobicity and macromolecular network structure. In this work, WG was subjected to a series of Na2SO3 solution, followed by cross-linking with PSV under transglutaminase (TGase) catalyzation. The results showed that Na2SO3 could break disulfide bonds of WG and increase its solubility from 7.33% to 42.82% with 1200 mg/L of Na2SO3. Correspondingly, the cross-linking degree was significantly enhanced. Compared to PSV, the cross-linked PSV-WG exhibited a higher surface hydrophobicity and thermal stability, with a lower zeta potential and apparent viscosity. The emulsifying activity of PSV-WG reached 17.42, 20.63 and 20.28 m2/g with Na2SO3 concentration of 300, 600 and 900 mg/L, which were all higher than that of PSV (15.19 m2/g). This work provided a novel strategy to elevate emulsifying properties of PSV by cross-link reaction.

Effects of short-term fermentation with lactic acid bacteria on the characterization, rheological and emulsifying properties of egg yolk.

Lactic acid bacteria fermentation is a safe and green technology that can modify the function of food ingredients (including proteins). In this article, egg yolks were subjected to fermentation with commercial lactic acid bacteria for 0, 3, 6 and 9 h, respectively. After fermentation treatment, the microbial composition has changed obviously (Streptococcus thermophilus increased significantly). The free sulfhydryl group (SH) contents and surface hydrophobicity of egg yolk proteins were significantly reduced. The rheological results indicated that the treated egg yolks possessed a decreased apparent viscosity. Correspondingly, the emulsifying activity of egg yolk was enhanced from 9.07 to 19.55, 23.40 and 24.61 m2/g for 3, 6 and 9 h of fermentation, respectively. And the emulsifying stability reached the maximum after 3 h of fermentation. This study investigated the relationship between structure and properties of yolk proteins, and showed that lactic acid fermentation endued egg yolk with better emulsifying properties.