Damage of polyethylene microplastics on the intestine multilayer barrier, blood cell immune function and the repair effect of Leuconostoc mesenteroides DH in the large-scale loach (Paramisgurnus dabryanus).

Polyethylene microplastics (PE-MPs) has become a global concern due to their widespread distribution and hazardous properties in aquatic habitats. In this study, the accumulation effect of PE-MPs in the intestine of large-scale loach (Paramisgurnus dabryanus) was explored by adding different concentrations of PE-MPs to the water, the destination of PE-MPs after breaking the intestinal barrier and the effects caused. The collected data showed that PE-MPs accumulation for 21d altered the histomorphology and antioxidant enzyme activity of the intestine, induced dysbiosis of the intestinal flora. 10 mg/L of PE-MPs induced a significant increase in the transcript levels of intestinal immunity factors in loach after 21d of exposure. Moreover, the levels of diamine oxidase (DAO) and d-lactic acid (D-Lac) in the gut and serum of loach were significantly increased after exposure to PE-MPs at all concentrations (1, 5, 10 mg/L). Subsequently, the presence of PE-MPs was detected in the blood, suggesting that the disruption of the intestinal multilayer barrier allowed PE-MPs to spill into the circulation. The accumulation of PE-MPs (1,5,10 mg/L) in the blood led to massive apoptosis and necrosis of blood cells and activated phagocytosis in response to PE-MPs invasion. To alleviate the damage, this study further exposure the effect of probiotics on PE-MPs treated loach by adding Leuconostoc mesenteroides DH (109 CFU/g) to the feed. The results showed that DH significantly increased the intestinal index and reduced the levels of DAO and D-Lac. To investigate the reason, we followed the PE-MPs in the intestine and blood of the loach and found that the number of PE-MPs particles was significantly reduced in the probiotic group, while the PE-MPs content in the feces was elevated. Thus, we concluded that DH reducing the accumulation of PE-MPs in the intestinal by increases fecal PE-MPs, which in turn mitigates the damage to the intestinal barrier caused by PE-MPs, and reduces the amount of PE-MPs in the blood. This work offers a robust analysis to understand the mechanisms of damage to the intestinal barrier by MPs and the fate of MPs after escaping the intestinal barrier and provide a new perspective on the application of probiotics in mitigating PE-MPs toxicity.

Hydrogel Dressing Containing Basic Fibroblast Growth Factor Accelerating Chronic Wound Healing in Aged Mouse Model.

Due to the decreasing self-repairing ability, elder people are easier to form chronic wounds and suffer from slow and difficult wound healing. It is desirable to develop a novel wound dressing that can accelerate chronic wound healing in elderly subjects to decrease the pain of patients and save medical resources. In this work, Heparin and basic fibroblast growth factor(bFGF) were dissolved in the mixing solution of 4-arm acrylated polyethylene glycol and dithiothreitol to form hydrogel dressing in vitro at room temperature without any catalysts, which is convenient and easy to handle in clinic application. In vitro re-lease test shows the bFGF could be continuously released for at least 7 days, whereas the dressing surface integrity maintained for 3 days degradation in PBS solution. Three groups of treatments including bFGF-Gel, bFGF-Sol and control without any treatment were applied on the full-thickness wound on the 22 months old mice back. The wound closure rate and histological and immunohistochemical staining all illustrated that bFGF-Gel displayed a better wound healing effect than the other two groups. Thus, as-prepared hydrogel dressing seems supe-rior to current clinical treatment and more effective in elderly subjects, which shows promising potential to be applied in the clinic.

17ß-estradiol (E2) in membranes: Orientation and dynamic properties.

Non-genomic membrane effects of estrogens are of great interest because of the diverse biological activities they may elicit. To further our understanding of the molecular features of the interaction between estrogenic hormones and membrane bilayers, we have determined the preferred orientation, location, and dynamic properties of 17ß-estradiol (E2) in two different phospholipid membrane environments using (2)H-NMR and 2D (1)H-(13)C HSQC in conjunction with molecular dynamics simulations. Unequivocal spectral assignments to specific (2)H labels were made possible by synthesizing six selectively deuterated E2 molecules. The data allow us to conclude that the E2 molecule adopts a nearly "horizontal" orientation in the membrane bilayer with its long axis essentially perpendicular to the lipid acyl-chains. All four rings of the E2 molecule are located near the membrane interface, allowing both the E2 3-OH and the 17ß-OH groups to engage in hydrogen bonding and electrostatic interactions with polar phospholipid groups. The findings augment our knowledge of the molecular interactions between E2 and membrane bilayer and highlight the asymmetric nature of the dynamic motions of the rigid E2 molecule in a membrane environment.

Correlation of morning dry mouth with clinical features of OSA in a community population: a cross-sectional study.

OBJECTIVES: Morning dry mouth, commonly seen in Obstructive Sleep Apnea (OSA) patients, is absent in current OSA screening tools. This study evaluated the link between morning dry mouth and OSA's clinical symptoms and complications, aiming to determine its viability as a screening indicator. METHODS: This research analyses baseline data from a prospective cohort study (the PIFCOPD study). Demographic information, medical history, and the presence of morning dry mouth symptoms were collected. The STOP-Bang questionnaire was performed for OSA screening. Logistic regression analyses were employed to establish the correlations between morning dry mouth and the clinical symptoms and comorbidities of OSA. RESULT: 1291 participants (62.1±7.5 years; 501 males, 790 females) were included, of which 416 reported morning dry mouth (32.2%). 42.6% in the high-risk OSA group and 22.1% in the low-risk group reported morning dry mouth. Individuals with morning dry mouth also showed higher STOP-Bang scores (3.3±1.6 vs. 2.3±1.4, P<0.01). Significant associations were found between morning dry mouth and loud snoring, observed sleep apnea, daytime fatigue, and hyperlipidemia (P<0.01), but not with alcohol consumption, tea consumption, diabetes, or hypertension. CONCLUSION: Morning dry mouth is associated with increased OSA risk and its clinical signs, suggesting its potential as an OSA screening symptom. CLINICAL TRIAL REGISTRATION: This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03532893) on 21 May 2018.

Primary cilia mediate skeletogenic BMP and Hedgehog signaling in heterotopic ossification.

Heterotopic ossification (HO), defined as the formation of extraskeletal bone in muscle and soft tissues, is a diverse pathological process caused by either genetic mutations or inciting trauma. Fibrodysplasia ossificans progressiva (FOP) is a genetic form of HO caused by mutations in the bone morphogenetic protein (BMP) type I receptor gene activin A receptor type 1 (ACVR1). These mutations make ACVR1 hypersensitive to BMP and responsive to activin A. Hedgehog (Hh) signaling also contributes to HO development. However, the exact pathophysiology of how skeletogenic cells contribute to endochondral ossification in FOP remains unknown. Here, we showed that the wild-type or FOP-mutant ACVR1 localized in the cilia of stem cells from human exfoliated deciduous teeth with key FOP signaling components, including activin A receptor type 2A/2B, SMAD family member 1/5, and FK506-binding protein 12kD. Cilia suppression by deletion of intraflagellar transport 88 or ADP ribosylation factor like GTPase 3 effectively inhibited pathological BMP and Hh signaling, subdued aberrant chondro-osteogenic differentiation in primary mouse or human FOP cells, and diminished in vivo extraskeletal ossification in Acvr1Q207D, Sox2-Cre; Acvr1R206H/+ FOP mice and in burn tenotomy-treated wild-type mice. Our results provide a rationale for early and localized suppression of cilia in affected tissues after injury as a therapeutic strategy against either genetic or acquired HO.

Well-aligned three-dimensional silk fibroin protein scaffold for orientation regulation of cells.

The similar characteristics of biomaterials to the extracellular matrix are essential for efficient tissue repair through dictating cell behaviors. But the scaffold fabrication with complex shapes and controlled alignment have proven to be a difficult task. Herein, a well-designed three-dimensional silk fibroin scaffold is fabricated through ice template technology. The effect of the silk fibroin protein concentration and the freezing temperature on the microstructure and mechanical properties of scaffolds are investigated systematically. Cells behavior mediated by the obtained silk fibroin scaffolds is detected. The results show that the protein concentration plays a vital role in microstructure and scaffold strength. A well-aligned scaffold can be obtained when silk fibroin solution is kept at 12 wt%, which holds the highest mechanical properties. The pore size can be further adjusted in the range of 5-80 µm by changing the freezing temperature from -60 to -196 °C. The well-oriented scaffold with the appropriate pore size of 10-20 µm has the best ability to guide cell alignment. The resulting scaffolds provide an excellent matrix to guide cells behaviors and have a potential application in tissue engineering.

Modified STOP-bang questionnaire incorporating morning dry mouth and BMI adjustment in China: a retrospective study of 590 patients.

BACKGROUND: Morning dry mouth (MDM) is a common symptom of Obstructive Sleep Apnea (OSA) yet current OSA screening tools overlook it. OBJECTIVE: To enhance the specificity of the Stop-Bang questionnaire (SBQ) by adding an MDM symptom. METHOD: A retrospective analysis on 590 patients from Peking University First Hospital (2013-2018) suspected of OSA was conducted. They underwent polysomnography. The research incorporated the MDM symptom into SBQ and adjusted the body mass index (BMI) threshold to 28 kg/m2. Predictive parameters were then calculated. RESULTS: 83.1% patients were diagnosed with OSA, with 61.4% reporting MDM. Multivariate regression confirmed MDM significantly influenced Apnea-Hypopnea Index (AHI). Adjusted SBQ with MDM showed a slight decrease in sensitivity but improved specificity, especially when using a BMI threshold of > 28 kg/m2. For AHI ≥ 5 events/h and AHI ≥ 15 events/h, adjusted SBQ with MDM (BMI >28 kg/m2) obtained the highest Youden index. CONCLUSION: Incorporating the MDM symptom into SBQ and adjusting the BMI threshold enhances the diagnostic specificity for OSA.

Reproductive toxicity and cross-generational effect of polyethylene microplastics in Paramisgurnus dabryanus.

Pollution of microplastics (MPs) has become a global environmental issue due to the difficulty in its degradation and may cause unexpected ecological effects. Nevertheless, little is known about the potential effects of MPs on reproduction toxicity in aquatic species. In this study, adult loach (Paramisgurnus dabryanus, F0 generation) were exposed to two concentrations (1 and 10 mg/L) of polyethylene MPs (PE-MPs) for 15 or 30 days, and the toxic effects in parental loach and the offspring (F1 generation) were examined. Our results showed that PE-MPs exposure could change the indicators content of antioxidant system in the brain, liver, and gonad. PE-MPs can accumulate in the gonads, disrupt the transcription of HPG-axis related genes, alter sex hormone levels, increase cell apoptosis and gonadal pathological lesions, lead to the damage of biological characteristics of semen, and affect the reproduction in F0 generation. PE-MPs remaining in the parental gonads can be transferred to the F1 generation embryos and accumulated on the embryonic chorionic membrane, increasing mortality and malformation rates, accelerating hatching time, and decreasing hatching rate and body length. These results suggest that PE-MPs leads to a potential adverse influence on reproduction and serious impacts on population sustainability. This work provides a new perspective into the effects of MPs on reproductive damage and cross-generational effects in teleost fish, which have implications in fields of freshwater ecology and environmental toxicology.

Effects of different lignocellulosic wastes on alleviating acidification of L-lactic acid production from food waste fermentation.

In this study, the effects of different lignocellulosic wastes on alleviating acidification in the fermentation of lactic acid (LA) from food waste (FW) were studied. Amongst three lignocellulosic wastes, spent mushroom substance (SMS) could reach 95.22% lignin removal efficiency through simple NaOH pretreatment. Results showed pretreated SMS was best choice for FW co-fermentation, the maximum LA concentration could reach 46.12 g/L. And the NaOH solution as neutraliser could save 5.69 mL compared with the other two lignocellulosic wastes. The reason for alleviating acidification was 4.71% calcium salt in SMS and the porous structure of SMS. Then, 50% of pretreated liquid (PL) produced in SMS pretreatment was reused in the co-fermentation process. Compared with the group with 0% PL loading, that with 50% PL loading showed an increase in LA concentration and optical purity of L-LA, reaching 50.95 g/L and 96.28%, and NaOH consumption also further decreased by 24.65%.

Bacterial cellulose production from terylene ammonia hydrolysate by Taonella mepensis WT-6.

Hydrothermal degradation was used to pretreat terylene with an aim of noticeably improving the yield of fermentable monomers: terephthalic acid (TPA), mono (2- hydroxyethyl) terephthalic acid (MHET), bis-hydroxyethyl terephthalate (BHET), and ethylene glycol (EG). After 0.5 h of reaction time at 180 °C, hydrothermal degradation with ammonia led to almost complete conversion of the terylene to TPA, MHET, BHET and EG, which were then transformed by Taonella mepensis WT-6 to bacterial cellulose (BC). Furthermore, the optimum fermentation conditions with the maximum BC yield were 5.0 g/L yeast extract, 30.0 °C, pH 9.0, 8.0% inoculum, and hydrolysate TOC (5.02 g/L). Additionally, mechanical and thermal analysis revealed that the properties of BC produced from TAH medium were similar to those of BC produced with HS medium. Considering the substantial amount of global terylene waste being produced, this study provides an alternative solution for the biosynthesis of BC.

Comparative Study of the Adverse Events Associated With Adjuvant Use of Dexmedetomidine and Clonidine in Local Anesthesia.

Background: Although clonidine and dexmedetomidine are used as alpha-2 agonists to improve the quality and duration of blockade induced by local anesthetics, no study has been reported to compare their associated adverse events in local anesthesia. The aim of this study is to compare the adverse events associated with the adjuvant use of dexmedetomidine and clonidine in local anesthesia. Methods: A comprehensive search was performed to retrieve any reported adverse event associated with adjuvant use of dexmedetomidine and clonidine in local anesthesia from published literature up to 1 July 2020. Assessment of the quality of included studies was performed by the Jadad score. A comparison of any reported adverse event was made between interventions by pooling data from studies using a direct meta-analysis technique. Dichotomous outcomes were summarized as risk ratios. The review was performed according to PRISMA guideline. Results: From 121 articles retrieved from the search finally 14 articles including 1,120 patients had eligibility criteria for including in the meta-analysis. No significant difference was observed between bradycardia/hypotension (OR = 1.17; 95 % CI = 0.66-2.10; P = 0.580; I 2 = 53.78 %, P = 0.027), nausea/vomiting (OR = 0.91; 95% CI = 0.59-1.42; P = 0.706; I 2 = 0.0 %, P = 0.940) dizziness/headache (OR = 1.10; 95% CI = 0.44-2.75; P = 0.831; I 2 = 0.0 %, P = 0.882) shivering (OR = 0.95 % CI = 0.50-1.66; P = 0.831; I 2 = 0.0 %, P = 0.920) and dry mouth (OR = 1.00; 95 % CI = 0.50-1.96; P = 0.996; I 2 = 0.0%, P = 0.900). No significant difference was observed in subgroup comparison of adverse events in the intravenous or local adjuvant use of the study drugs (p > 0.05). Conclusion: There is no difference in adverse events associated with the intravenous or local adjuvant use of dexmedetomidine and clonidine in local anesthesia.

A novel strategy for tumor therapy: targeted, PAA-functionalized nano-hydroxyapatite nanomedicine.

The rapid development of nanotechnology has provided new strategies for the treatment of tumors. Nano-scale hydroxyapatite (HAP), as the main component of hard tissues in humans and vertebrates, have been found to specifically inhibit tumor cells. However, achieving controllable synthesis of HAP and endowing it with cancer cell-targeting properties remain enormous challenges. To solve this problem, we developed polyacrylic acid-coordinated hydroxyapatite nanoparticles (HAP-PAA) and further chemically grafted them with folic acid (HAP-PAA-FA) for cancer treatment in this study. The nucleation sites and steric hindrance provided by the PAA greatly inhibited the agglomeration of the nanoparticles, and at the same time, the excess functional groups further modified the surface of nanoparticles to achieve targeting efficiency. The spherical, low-crystallinity HAP-PAA nanoparticles exhibited good tumor cell lethality. After grafting the nanoparticles with folic acid for molecular targeting, their cellular uptake and specific killing ability of tumor cells were further enhanced. The HAP-PAA-FA nanoparticle system exerted a regulatory effect on the tumor microenvironment and had good biological safety. All the above results indicate that this research will broaden the application of hydroxyapatite in tumor treatment.

Core/Shell PEGS/HA Hybrid Nanoparticle Via Micelle-Coordinated Mineralization for Tumor-Specific Therapy.

Nanomicelles, by virtue of their prominent biocompatibility, degradability, and ability to solubilize hydrophobic drugs, have been widely used as the most effective delivery platform for anticancer drugs. However, undesirable drug-loading capacity, unfeasible modification, poor in vivo stability, and intratumoral penetration remain to be addressed. Herein, we introduce a novel core/shell PEGylated poly(glycerol sebacate) (PEGS)/hydroxyapatite (HA) hybrid nanomicelle based on a unique triblock PEGS substrate with functional carboxyls in terminals and free hydroxyls as pendant groups. The hydrophobic doxorubicin (DOX) can be controllably encapsulated in the core of nanomicelles via hydrogen bonding, and ensuing in situ mineralization of HA occurs as a shell layer with the electrostatic effect between the carboxylate radical (COO-) and calcium ion (Ca2+). Through optimizing the coordination of PEGS nanomicelles and HA mineralization, 20-30 nm spherical nanoparticles can be formed with considerable drug loading (0.38 mg DOX/1 mg nanoparticles) and a sensitive pH-responsive release (about 50% release amount at pH 5.6 while <5% release amount at pH 7.4 in 24 h). In further in vitro studies, this PEGS/HA hybrid nanoparticle system exhibits excellent selective tumor inhibitory efficacy, while in in vivo studies, high efficacy of tumor suppression and low incidence of toxicity can be evidenced in a DOX-loaded PEGS/HA group (71.7% decrease in average tumor volume compared to a control group after 15 day hypodermic treatment). The core/shell PEGS/HA nanoparticle coordinated with PEGS nanomicelles and in situ HA mineralization represents high drug-loading capacity, multifunctional possibility, and tumor-selective and responsive release profiles and could offer a highly promising platform for tumor therapy in clinical application.

Bioinspired, Injectable, Quaternized Hydroxyethyl Cellulose Composite Hydrogel Coordinated by Mesocellular Silica Foam for Rapid, Noncompressible Hemostasis and Wound Healing.

Massive bleeding control and anti-infection are the major challenges for urgent trauma with deep and noncompressible hemorrhage in both clinic and battlefield. Inspired by the coordinated primarily blood clot formation and secondly coagulation cascade activation in natural hemostasis process, an injectable, quaternized hydroxyethyl cellulose/mesocellular silica foam (MCF) hydrogel sponge (QHM) for both hemorrhage control and antibacterial activities were prepared via one-pot radical graft copolymerization. The as-prepared QHMs exhibited instant water-triggered expansion and superabsorbent capacity and thereby effectively facilitated blood components concentration. Moreover, the QHM1 with appropriate amount of MCF (9.82 w/w %) could further activate the coagulation factors. Synergistically, the QHM1 could reduce the plasma clotting time to 59 ± 4% in vitro and showed less blood loss than commercially available hemostatics in vivo noncompressible hemorrhage models of lethal rabbit-liver defect. Furthermore, the QHM with a quaternary ammonium groups density of 2.732 mmol/g exhibited remarkable antibacterial activities and excellent cytocompatibility. With the efficient hemostasis efficacy and excellent antibacterial behavior, QHM dramatically facilitated the wound healing in a full-thickness skin defect model in vivo. Thus, this QHM represents a promising hemostatic in more widespread clinical application.

Self-Assembled Injectable Nanocomposite Hydrogels Coordinated by in Situ Generated CaP Nanoparticles for Bone Regeneration.

Due to the great similarity to the natural extracellular matrix and minimally invasive surgeries, injectable hydrogels are appealing biomaterials in cartilage and bone tissue engineering. Nevertheless, undesirable mechanical properties and bioactivity greatly hamper their availability in clinic applications. Here, we developed an injectable nanocomposite hydrogel by in situ growth of CaP nanoparticles (ICPNs) during the free-radical polymerization of dimethylaminoethyl methacrylate (DMAEMA) and 2-hydroxyethyl methacrylate (HEMA) matrix (PDH) for bone regeneration. The ICPNs are self-assembled by incorporation of poly-l-glutamic acid (PGA) with abundant carboxyl functional groups during the formation of carboxyl-Ca2+ coordination and further CaP precipitation. Furthermore, the carboxyl groups of PGA could interact with the tertiary amines of DMAEMA fragments and thus improve the mechanical strength of hydrogels. Upon mixing solutions of DMAEMA and HEMA bearing PGA, Ca2+, and PO43-, this effective and dynamic coordination led to the rapid self-assembly of CaP NPs and PDH nanocomposite hydrogels (PDH/mICPN). The obtained optimal nanocomposite hydrogels exhibited suitable injectable time, an enhanced tensile strength of 321.1 kPa, and a fracture energy of 29.0 kJ/m2 and dramatically facilitated cell adhesion and upregulated osteodifferentiation compared to hydrogels prepared by blending ex situ prefabricated CaP NPs. In vivo experiments confirmed the promoted osteogenesis, which shows a striking contrast to pure PDH hydrogels. Additionally, the methacrylate groups on the monomers could easily be functionalized with aptamers and thereby facilitate recognition and capturing of bone marrow stromal cells both in vitro and in vivo and strengthen the bone regeneration. We believe that our conducted research about in situ self-assembled CaP nanoparticle-coordinated hydrogels will open a new avenue for bone regeneration in the future endeavors.

Natural or Natural-Synthetic Hybrid Polymer-Based Fluorescent Polymeric Materials for Bio-imaging-Related Applications.

Fluorescent polymeric materials such as hydrogels and particles have been attracting attention in many biomedical applications including bio-imaging, optical sensing, tissue engineering, due to their good biocompatibility, biodegradability, and advanced optical property. This review article aims at summarizing recent progress in fluorescent hydrogels and particles based on natural polymers or natural-synthetic hybrid polymers as the building blocks with a concentration on their bio-imaging-related applications. The challenges and future perspectives for the development of natural or natural-synthetic hybrid polymer-based fluorescent hydrogels and particles are also presented.

Solid lipid nanoparticles coated with cross-linked polymeric double layer for oral delivery of curcumin.

Solid lipid nanoparticles (SLNs) are regarded as promising carriers to improve the safety and effectiveness of delivery for drugs and nutrients, however, the clinic applications for oral administration are limited by their poor stability in gastrointestinal conditions. In this study, surface modification was explored to confer new physicochemical properties to SLNs and thus achieve enhanced functionalities. Novel SLNs with biopolymeric double layer (DL) coating using two natural biopolymers, i.e. caseinate (NaCas) and pectin, were prepared to encapsulate and deliver curcumin, a lipophilic bioactive compound studied as a model drug/nutrient. The DL coating was chemically cross-linked by creating covalent bonds between NaCas and pectin, using two different cross-linkers, i.e. glutaraldehyde (GA) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-Hydroxysuccinimide (EDC/NHS). Prior to cross-linking, the mean particle size, polydispersity index and zeta potential of DL-SLNs were 300-330nm, 0.25-0.30, -45-40mV, respectively. It was found that cross-linking with GA had a more prominent effect on particle size and polydispersity index than EDC/NHS. The cross-linking process significantly improved physicochemical properties of DL-SLNs, resulting in higher encapsulation efficiency and loading capacity, better stability and slower release profile in simulated gastrointestinal conditions. Particularly, an optimal zero-order release kinetic was observed for EDC/NHS crosslinked DL-SLNs. The electron microscopy revealed that both cross-linked DL-SLNs exhibited spherical shape with homogeneous size and smooth surface. Encapsulation of curcumin in SLNs dramatically enhanced its antioxidant activity in aqueous condition. The cross-linking process further helped spray drying of SLNs by forming homogenous powder particles. These results indicated that coating with cross-linked polymers could significantly improve the physicochemical properties of SLNs and expand their potentials as oral delivery systems for lipophilic nutrients and drugs.

Repetitive Biomimetic Self-healing of Ca(2+)-Induced Nanocomposite Protein Hydrogels.

Self-healing is a capacity observed in most biological systems in which the healing processes are autonomously triggered after the damage. Inspired by this natural behavior, researchers believed that a synthetic material possessing similar self-recovery capability could also be developed. Albeit various intrinsic self-healing systems have been developed over the past few decades, restriction on the biocompatibility due to the required synthetic conditions under extreme pH and with poisonous cross-linker significantly limits their application in biomedical field. In this study, a highly biocompatible nanocomposite protein hydrogel with excellent biomimetic self-healing property is presented. The self-healing protein gel is made by inducing calcium ions into the mixture of heat-induced BSA nano-aggregates and pristine BSA molecules at room temperature and under physiological pH due to the ion-mediated protein-protein association and the bridging effect of divalent Ca(2+) ions. The as-prepared protein hydrogel shows excellent repetitive self-healing properties without using any external stimuli at ambient condition. Such outstanding self-recovery performance was quantitatively evaluated/validated by both dynamic and oscillatory rheological analysis. Moreover, with the presence of calcium ions, the self-healing behavior can be significantly facilitated/enhanced. Finally, the superior biocompatibility demonstrated by in vitro cytotoxicity analysis suggests that it is a promising self-healing material well-suited for biomedical applications.

A Biocompatible and Biodegradable Protein Hydrogel with Green and Red Autofluorescence: Preparation, Characterization and In Vivo Biodegradation Tracking and Modeling.

Because of its good biocompatibility and biodegradability, albumins such as bovine serum albumin (BSA) and human serum albumin (HSA) have found a wide range of biomedical applications. Herein, we report that glutaraldehyde cross-linked BSA (or HSA) forms a novel fluorescent biological hydrogel, exhibiting new green and red autofluorescence in vitro and in vivo without the use of any additional fluorescent labels. UV-vis spectra studies, in conjunction with the fluorescence spectra studies including emission, excitation and synchronous scans, indicated that three classes of fluorescent compounds are presumably formed during the gelation process. SEM, FTIR and mechanical tests were further employed to investigate the morphology, the specific chemical structures and the mechanical strength of the as-prepared autofluorescent hydrogel, respectively. Its biocompatibility and biodegradability were also demonstrated through extensive in vitro and in vivo studies. More interestingly, the strong red autofluorescence of the as-prepared hydrogel allows for conveniently and non-invasively tracking and modeling its in vivo degradation based on the time-dependent fluorescent images of mice. A mathematical model was proposed and was in good agreement with the experimental results. The developed facile strategy to prepare novel biocompatible and biodegradable autofluorescent protein hydrogels could significantly expand the scope of protein hydrogels in biomedical applications.

Multifunctional liposomes constituting microneedles induced robust systemic and mucosal immunoresponses against the loaded antigens via oral mucosal vaccination.

To develop effective, convenient and stable mucosal vaccines, mannose-PEG-cholesterol (MPC)/lipid A-liposomes (MLLs) entrapping model antigen bovine serum albumin (BSA) were prepared by the procedure of emulsification-lyophilization and used to constitute microneedles, forming the proMLL-filled microneedle arrays (proMMAs). The proMMAs were rather stable and hard enough to pierce porcine skin and, upon rehydration, dissolved rapidly recovering the MLLs without size and entrapment change. The proMMAs given to mice via oral mucosal (o.m.) route, rather than routine intradermal administration, elicited robust systemic and mucosal immunoresponses against the loaded antigens as evidenced by high levels of BSA-specific IgG in the sera and IgA in the salivary, intestinal and vaginal secretions of mice. Enhanced levels of IgG2a and IFN-γ in treated mice revealed that proMMAs induced a mixed Th1/Th2 immunoresponse. Moreover, a significant increase in CD8(+) T cells confirmed that strong cellular immunity had also been established by the immunization of the proMMAs. Thus, the proMMAs can be immunized via o.m. route to set up an effective multiple defense against pathogen invasion and may be an effective vaccine adjuvant-delivery system (VADS) applicable in the controlled temperature chain.