Comparison of invisalign mandibular advancement and twin-block on upper airway and hyoid bone position improvements for skeletal class II children: a retrospective study.

BACKGROUND: This study is to evaluate and compare the improvement of upper airway morphology and hyoid bone position in children with Class II mandibular retrusion treated with Invisalign mandibular advancement (MA) and Twin-Block (TB) appliances, utilizing cone beam computed tomography (CBCT). METHODS: 32 children aged between 8 and 11.5 years old were included in this study, with an average age of 10.2 years old. These children were divided into two groups, MA and TB, with 16 children in each group. Changes in upper airway morphology and hyoid bone position before and after treatment were analyzed using CBCT. RESULTS: (1) Changes in upper airway before and after treatment: the oropharynx volume (Or-V), the oropharynx minimum cross-sectional area (Or-mCSA), the hypopharynx volume (Hy-V), and the hypopharynx minimum cross-sectional area (Hy-mCSA) in both the MA and TB groups increased after treatment, and the differences were statistically significant (P < 0.05) compared to pre-treatment status. (2) Changes in hyoid bone position before and after treatment: The distances between H point and third cervical vertebra (H-C3), H point and pogonion (H-RGN), H point and mandibular plane (H-MP), H point and Frankfort horizontal plane (H-FH), H and S point (H-S), and H point and palatal plane (H-PP) in both the MA and TB groups increased after treatment, and the differences were statistically significant (P < 0.05). CONCLUSION: Both MA and TB appliances effectively improved the structural narrowness of the upper airway and reduced respiratory resistance, thus improving breath quality. However, MA showed more effectiveness in improving the narrowest part of the hypopharynx compared to TB. Both appliances also promoted anterior downward movement of the hyoid bone, which opens the upper airway of the oropharynx and hypopharynx and helps the upper airway morphology return to normal range.

A retrospective analysis of dental implant survival in HIV patients.

AIM: This 5 years retrospective cohort survival study compared failure rates of dental implants placed in HIV (+) and HIV (-) patients relative to several risk factors. MATERIALS AND METHODS: Between 2006 and 2015, 484 implants placed in HIV (+) patients and 805 implants placed in HIV (-) patients were assessed for survival. The effects of HIV were estimated using propensity weighting. The effects of age, smoking status, diabetes, restoration status, gender, implant type, placement site, hepatitis C status, baseline CD4 count and CD4%, post-placement average CD4%, nadir CD4%, nadir CD4 count and antiviral therapy were analysed. RESULTS: Implants placed in HIV (+) patients and HIV (-) patients had similar failure rates (HR = 1.4, p = 0.34). Increased failure rates were observed in HIV (+) patients with baseline CD4% ≤20 (HR = 2.72, p = 0.04), post-placement CD4% average ≤20% (HR = 2.71, p = 0.04), protease inhibitor administration (HR = 2.74, p = 0.04), smoking (HR = 2.61, p = 0.05) and anterior maxillary placement (HR = 5.82, p < 0.01). Hepatitis C coinfection, viral titre, baseline CD4 count, gender, implant type and restoration type were non-contributory. CONCLUSION: Implants placed in HIV (+) patients had similar survival rates as HIV (-) patients. Failure rates increase significantly when confounding risk factors are present in HIV (+) patients.

FGF adsorbed mesoporous bioactive glass with larger pores in enhancing bone tissue engineering.

Mesoporous bioactive glass (MBG) is performed as a bone tissue engineering material because of its good bioactivity, biocompatibility and osteoinducion characteristics. Here, we propose MBG with larger pores (MBG-L) adsorbed fibroblast growth factor (FGF) to facilitate osteoblast differentiation and matrix mineralization. Specifically, we observed that MBG-L promotes calcium deposit precipitation in vitro. In addition, adhesion, proliferation, differentiation and matrix mineralization were promoted after osteoblast cultured on MBG-L/FGF. Interestingly, we found that the transcriptional activity of the critical transcription factor Runx2 was increased through MAPK pathway after osteoblast cultured on MBG-L/FGF. Support for this result, we found that the expression of osteoblastic marker genes, Osteocalcin (Ocn), Osteopontin (Opn), and Runx2 were increased. Thus, our findings provided that MBG-L/FGF could be a promising new material in bone tissue engineering.

Pilot Study to Evaluate the Adjunct Use of a Povidone-Iodine Topical Antiseptic in Patients with Soft Tissue Abscesses.

BACKGROUND: Povidone-iodine (PVP-I) antiseptic solutions have been shown to be effective against methicillin-resistant Staphylococcal aureus, a common cause of superficial skin abscesses. OBJECTIVES: Our objective was to study the feasibility of using PVP-I as a treatment adjunct in patients with superficial skin abscesses and determine if it confers any benefit over incision and drainage (I&D) alone. METHODS: This was a randomized controlled pilot study of adult patients with an uncomplicated skin abscess. Patients were randomized to PVP-I or standard treatment. All patients had I&D and abscess packing. Patients randomized to PVP-I were instructed on daily application of the agent to hands, wound, and surrounding skin with dressing changes. Subjects returned at 48-72 h and 7-10 days and followed-up by phone at 30 days. The primary outcome was clinical cure 7-10 days after I&D. The secondary outcomes were rate of development of new skin lesions and spread in household contacts within 30 days. RESULTS: Clinical cure occurred in 91.3% of patients in the standard group vs. 88.2% of patients in the PVP-I group (difference, 3.1%; 95% confidence interval [CI] -10.7 to 16.8; p = 0.53). There was a significantly higher adverse event rate in the group who received PVP-I (59.6%) vs. standard care (26.5%) (difference 33.1%, 95% CI 13.2-50.2; p < 0.001). CONCLUSIONS: There was no difference in clinical cure rates among patients using PVP-I (88.2%) vs. standard care (91.3%) after I&D. There were no major adverse events, but the addition of PVP-I was commonly associated with local skin irritation.

Combination Glioma Therapy Mediated by a Dual-Targeted Delivery System Constructed Using OMCN-PEG-Pep22/DOX.

Accumulating studies have investigated the efficacy of receptor-mediated delivery of hydrophobic drugs in glioma chemotherapy. Here, a delivery vehicle comprising polyethylene glycol (PEG) and oxidized nanocrystalline mesoporous carbon particles (OMCN) linked to the Pep22 polypeptide targeting the low-density lipoprotein receptor (LDLR) is designed to generate a novel drug-loaded system, designated as OMCN-PEG-Pep22/DOX (OPPD). This system effectively targets glioma cells and the blood-brain barrier and exerts therapeutic efficacy through both near-infrared (NIR) photothermal and chemotherapeutic effects of loaded doxycycline (DOX). Pathological tissue microarrays show an association of LDLR overexpression in human glioma tissue with patient survival.NIR irradiation treatment and magnetic resonance imaging results show that OPPD reaches the effective glioma-killing temperature in a glioma-bearing rat with a skull bone removal model and considerably reduces glioma sizes relative to the drug-loaded system without the Pep22 peptide modification and the control respectively. Thus, OPPD not only effectively targets LDLR-overexpressing glioma but also exerts a dual therapeutic effect by transporting DOX into the glioma and generating thermal effects with near-infrared irradiation to kill tumor cells. These collective findings support the utility of the novel OPPD drug-loaded system as a promising drug delivery vehicle for clinical application in glioma therapy.

Targeted Ferroptosis-Immunotherapy Synergy: Enhanced Antiglioma Efficacy with Hybrid Nanovesicles Comprising NK Cell-Derived Exosomes and RSL3-Loaded Liposomes.

Ferroptosis therapy and immunotherapy have been widely used in cancer treatment. However, nonselective induction of ferroptosis in tumors is prone to immunosuppression, limiting the therapeutic effect of ferroptosis cancer treatment. To address this issue, this study reports a customized hybrid nanovesicle composed of NK cell-derived extracellular versicles and RSL3-loaded liposomes (hNRVs), aiming to establish a positive cycle between ferroptosis therapy and immunotherapy. Thanks to the enhanced permeability and retention effect and the tumor homing characteristics of NK exosomes, our data indicate that hNRVs can actively accumulate in tumors and enhance cellular uptake. FASL, IFN-γ, and RSL3 are released into the tumor microenvironment, where FASL derived from NK cells effectively lyses tumor cells. RSL3 downregulates the expression of GPX4 in the tumor, leading to the accumulation of LPO and ROS, and promotes ferroptosis in tumor cells. The accumulation of IFN-γ and TNF-α stimulates the maturation of dendritic cells and effectively induces the inactivation of GPX4, promoting lipid peroxidation, making them sensitive to ferroptosis and indirectly promoting the occurrence of ferroptosis. This study highlights the role of the customized hNRV platform in enhancing the effectiveness of synergistic treatment with selective delivery of ferroptosis inducers and immune activation against glioma without causing additional side effects on healthy organs.

Copper-Zinc-Doped Bilayer Bioactive Glasses Loaded Hydrogel with Spatiotemporal Immunomodulation Supports MRSA-Infected Wound Healing.

Developing biomaterials with antimicrobial and wound-healing activities for the treatment of wound infections remains challenging. Macrophages play non-negligible roles in healing infection-related wounds. In this study, a new sequential immunomodulatory approach is proposed to promote effective and rapid wound healing using a novel hybrid hydrogel dressing based on the immune characteristics of bacteria-associated wounds. The hydrogel dressing substrate is derived from a porcine dermal extracellular matrix (PADM) and loaded with a new class of bioactive glass nanoparticles (BGns) doped with copper (Cu) and zinc (Zn) ions (Cu-Zn BGns). This hybrid hydrogel demonstrates a controlled release of Cu2+ and Zn2+ and sequentially regulates the phenotypic transition of macrophages from M1 to M2 by alternately activating nucleotide-binding oligomerization domain (NOD) and inhibiting mitogen-activated protein kinases (MAPK) signaling pathways. Additionally, its dual-temporal bidirectional immunomodulatory function facilitates enhanced antibacterial activity and wound healing. Hence, this novel hydrogel is capable of safely and efficiently accelerating wound healing during infections. As such, the design strategy provides a new direction for exploring novel immunomodulatory biomaterials to address current clinical challenges related to the treatment of wound infections.

ATP-free in vitro biotransformation of starch-derived maltodextrin into poly-3-hydroxybutyrate via acetyl-CoA.

In vitro biotransformation (ivBT) facilitated by in vitro synthetic enzymatic biosystems (ivSEBs) has emerged as a highly promising biosynthetic platform. Several ivSEBs have been constructed to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA). However, some systems are hindered by their reliance on costly ATP, limiting their practicality. This study presents the design of an ATP-free ivSEB for one-pot PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate. Stoichiometric analysis indicates this ivSEB can self-maintain NADP+/NADPH balance and achieve a theoretical molar yield of 133.3%. Leveraging simple one-pot reactions, our ivSEBs achieved a near-theoretical molar yield of 125.5%, the highest PHB titer (208.3 mM, approximately 17.9 g/L) and the fastest PHB production rate (9.4 mM/h, approximately 0.8 g/L/h) among all the reported ivSEBs to date, and demonstrated easy scalability. This study unveils the promising potential of ivBT for the industrial-scale production of PHB and other acetyl-CoA-derived chemicals from starch.

Uptake of Nanoplastic particles by zebrafish embryos triggers the macrophage response at early developmental stage.

Plastic pollution continues to erupt as a global ecological concern. As plastic debris is degraded into nanoscale and microscale particles via biodegradation, UV-irradiation, and mechanical processes, nanoplastic pollution arises as a threat to virtually every biological and ecological system on the planet. In this study, zebrafish (Danio rerio) embryos were exposed to fluorescently labeled plastic particles at nanoscales (30 nm and 100 nm). The uptake of both the nanoplastic particles (NPs) was found to exponentially increase with incubation time. Penetration of NPs through the natural barrier of the zebrafish embryos, the chorion, was observed prior to the hatching of the embryo. As a result, the NPs were found to accumulate on the body surface as well as inside the body of the zebrafish. The invasion of NPs into zebrafish embryos induced the upregulation of several stress and immune response genes including interleukins (il6 and il1b), cytochrome P450 (cyp1a and cyp51), and reactive oxygen species (ROS) removal protein-encoding genes (sod and cat). This suggested the initiation of ROS generation and removal as well as the activation of the immune response of zebrafish embryos. Colocalization of macrophages and NPs in zebrafish embryos indicated the involvement of macrophage response to the NP invasion at the early developmental stage of zebrafish.

Development and characterization of DEC-205 receptor targeted Potentilla anserina L polysaccharide PLGA nanoparticles as an antigen delivery system to enhance in vitro and in vivo immune responses in mice.

Potentilla anserina L polysaccharide (PAP) is known to regulate immunity. Poly(lactic-co-glycolicacid) (PLGA) is a type of drug carrier with biocompatibility and biodegradable USFDA approved polymer, which possesses the advantages of high safety and good sustained-release effect. The DEC205 receptor, a type I membrane protein, is widely distributed on the surface of macrophages and dendritic cells (DCs) and plays a key role in antigen recognition and presentation. In this study, we prepared Potentilla anserina L polysaccharide PLGA nanoparticles targeting DEC205 receptor (DEC205-PAPP) and characterized the nanoparticles with regards to their effects on immune activation in vitro and in vivo. In vitro, DEC205-PAPP promoted the uptake activity of macrophages and increased the secretion of NO and cytokines (IFN-γ, IL-4, IL-6, and GM-CSF), up-regulated the expression of CD80+, CD86+. In vivo, DEC205-PAPP elevated the immune organ index, induced DC maturation, promoted T lymphocyte proliferation and differentiation, and increased the levels of antigen-specific IgG antibody and cytokines (IFN-γ, IL-4), which prolonged the residence time of the OVA antigen in the immune organs and the lymph nodes. In conclusion, DEC205-PAPP had a slow-release effect, induced humoral and cellular immune responses, and could potentially be used as an effective antigen-targeted delivery system.

Enhancement of the immune response via the facilitation of dendritic cell maturation by CD-205 Receptor-mediated Long-circling liposomes acting as an antigen and astragalus polysaccharide delivery system.

CD-205 receptor-mediated dendritic cell (DC) targeting liposomes are commonly used as a delivery system for inducing a strong T-cell immune response or specific immune tolerance. This delivery system can carry both the antigen and adjuvant, thereby modulating DC maturation and also activating the T-cell response. In order to maximize the desired therapeutic effects of Astragalus polysaccharides (APS) and induce an efficient cellular and humoral immune response against the antigen, ovalbumin (OVA) and APS were encapsulated in long-circling liposomes conjugated with anti-CD-205 receptor antibodies to produce CD-205-targeted liposomes (iLPSM). We explored using a series of experiments evaluating the targeting efficiency of iLPSM. In vitro, iLPSM nanoparticles promoted the proliferation of macrophages, and the nanoparticles were rapidly phagocytized by macrophages. In vivo, iLPSM significantly improved the antibody titers of OVA-specific IgG and IgG, isotypes cytokine production, and T and B lymphocyte differentiation. Furthermore, iLPSM facilitated the maturation of DCs. In addition, iLPSM nanoparticles could prolong the retention time of nanoparticles at the injection site, leading to a strong, sustained immune response. These results show that the CD-205 antibody successfully binds to the corresponding cell receptor.

DEC-205 receptor targeted poly(lactic-co-glycolic acid) nanoparticles containing Eucommia ulmoides polysaccharide enhances the immune response of foot-and-mouth disease vaccine in mice.

Nanoparticles targeting the DEC-205 receptor were found to induce antigen-specific protective immune response. When the delivery system carries both antigens and immunomodulators, it can maximize the expected therapeutic effect of the drug and induce effective humoral and cellular immune responses to antigens.In this study, we encapsulated the Eucommia ulmoides Oliv. polysaccharides (EUPS) into PLGA nanoparticles (NPs) and conjugated it with anti-CD205 monoclonal Ab (MAb) to produce a DEC-205 receptor targeted PLGA nanoparticles (anti-DEC-205-EUPS-PLGA NPs). The physicochemical characteristics and adjuvant activity of the above NPs were evaluated in vitro and in vivo. In the in vitro setting, 200 µg·mL-1 anti-DEC-205-EUPS-PLGA could improve the proliferation of DCs and promote their antigen up-take activity. In the in vivo setting, anti-DEC-205-EUPS-PLGA NPs remarkably controlled the release of drug and antigen to induce sustained immune responses and up-regulated the levels of FMDV-specific IgG antibodies, promoted the cytotoxic activity of CTLs and NK cells, and improved the proliferation of splenocytes. Moreover, the anti-DEC-205-EUPS-PLGA NPs facilitated the maturation of DCs. The above data indicated that anti-DEC-205-EUPS-PLGA NPs employed as an targeted adjuvant induced the humoral and cellular immune activity by promoting the maturation of DCs. These findings may provide a new insight onto the development of vaccine adjuvants.

2D Black Phosphorus-Based Cytomembrane Mimics with Stimuli-Responsive Antibacterial Action Inspired by Endotoxin-Associated Toxic Behavior.

Biomimetic membrane materials have been widely explored and developed for drug loading and tissue engineering applications due to their excellent biocompatibility and abundant reaction sites. However, novel cytomembrane mimics have been lacking for a long time. In this study, black phosphorus (BP) was used as the foundation for a new generation of promising cytomembrane mimics due to its multiple similarities to cytomembranes. Inspired by the dual function of endotoxins on membranes, we prepared a BP-based cytomembrane mimic with controllable antibacterial ability via electrostatic interaction between BP and [1-pentyl-1-quaternary ammonium-3-vinyl-imidazole]Br ([PQVI]Br). The release of PQVI could be manipulated in different conditions by adjusting the electrostatic force, thereby achieving controllable antibacterial ability. This report confirms the possibility of using BP as a new material to mimic cytomembranes and provides a new concept of controllable antibacterial action based on endotoxins.

Ridge preservation following tooth extraction using bovine xenograft compared with porcine xenograft: A randomized controlled clinical trial.

BACKGROUND: The primary purpose of this study was to histologically determine if there is a significant difference in new bone formation, residual graft material, and connective tissue/other when ridge preservation is accomplished using a bovine versus a porcine xenograft. METHODS: Forty-four patients needing a single rooted tooth extraction and ridge preservation in preparation for dental implant placement were recruited in the study. After minimally traumatic tooth extraction, alveolar ridge dimensions were measured using a custom-fabricated acrylic stent. Patients were then randomized 1:1 to receive ridge preservation using either bovine or porcine xenograft material. A trimmed dense polytetrafluoroethylene (d-PTFE) membrane was overlaid on the graft material, the mucoperiosteal flaps were replaced, and the surgical site was sutured. After 18 to 20 weeks of wound healing, sites were surgically re-entered, ridge dimensions were again measured using the previously fabricated acrylic stents and a bone core sample of the grafted site was harvested for histomorphometric analysis. RESULTS: Thirty eight of the 44 enrolled patients completed the study, 17 from the bovine group and 21 from the porcine group. Histologically, there were no statistically significant differences between the groups for mean percentage of vital bone formation (bovine = 36.21%, porcine = 31.27%, P = 0.49), residual graft material (bovine = 20.47%, porcine = 19.52%, P = 0.82) and connective tissue/other (bovine = 43.32%, porcine = 49.21%, P = 0.19). For secondary outcomes, there were no significant differences between the groups for mean change in buccal ridge height, lingual ridge height, and ridge width. However, a higher number of patients in the porcine group had additional grafting at the time of implant placement, either because of thin buccal plate or failure of implant stability. CONCLUSION: The findings suggest that ridge preservation with porcine xenograft results in comparable histomorphometric outcomes and dimensional stability with bovine xenograft.

DEC-205 receptor-mediated long-circling nanoliposome as an antigen and Eucommia ulmoides polysaccharide delivery system enhances the immune response via facilitating dendritic cells maturation.

DEC-205 receptor-mediated dendritic cells (DC) targeting nanoliposomes is a promising delivery system in eliciting an immune response against pathogens. When this delivery system carries both antigen and immunomodulator, it can effectively regulate the DC function as well as the initial T cell response. To maximize the desired therapeutic effects of Eucommia ulmoides Oliv. polysaccharides (EUPS), and induce an efficient humoral and cellular immune response against an antigen, we encapsulated the OVA and EUPS in long-circling nanoliposomes and conjugated it with anti-DEC-205 receptor antibody to obtain a DEC-205-targeted nanoliposomes (anti-DEC-205-EUPS-OVA-LPSM). The physicochemical properties and immune-modulating effects were investigated in vitro and in vivo by a series of the experiment to evaluate the targeting efficiency of anti-DEC-205-EUPS-OVA-LPSM. In vitro, anti-DEC-205-EUPS-OVA-LPSM (160 µg mL-1) could enhance DCs proliferation and increase their phagocytic efficiency. In vivo anti-DEC-205-EUPS-OVA-LPSM remarkably promoted the OVA-specific IgG and IgG isotypes levels, enhanced the splenocyte proliferation, and induced the NK cell and CTL cytotoxicity. Besides, the anti-DEC-205-EUPS-OVA-LPSM enhanced the maturation of DCs. These findings suggest that the DEC-205 receptor antibody-conjugated EUPS nanoliposome can act as an efficient antigen delivery system to enhance the cellular and humoral immune response by promoting DC maturation. This indicates that the anti-DEC-205-EUPS-OVA-LPSM has significant potential as an immune-enhancing agent and antigen delivery system.

Evaluation of the diagnostic performance and its associated factors of a commercial anti-EV-A71 IgM-capture ELISA kit in hospitalized children with clinical diagnostic HFMD.

OBJECTIVES: Enterovirus A71 (EV-A71) is the main pathogen of severe hand, foot, and mouth disease (HFMD). Commercial enzyme-linked immunosorbent assays (ELISAs) are widely used in Chinese hospitals for the rapid diagnosis of acute EV-A71 infections. We present an evaluation of the diagnostic performance of a commercial anti-EV-A71 IgM-capture ELISA kit. METHODS: A prospective, hospital-based HFMD cohort was established in Henan Children's Hospital (February 2017 - February 2018). Stool and blood specimens were collected from 1413 participants for diagnosing EVA71 by quantitative Real-Time Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and anti-EV-A71 ELISA. RESULTS: Detection yields of EV-A71 IgM increased from 6.5 % (95 % CI:3.3 %-11.4 %) at 0∼24 h, to 42 % (95 % CI:28.3 %-57.8) at 120∼144 h from onset to sampling, and stabilized at ∼40 % after 144 h. With increased time from onset to sampling, the sensitivity of the commercial ELISA increased from 0.54 (95 % CI:0.25-0.81) to 0.74 (95 % CI:0.43-0.66), while specificity decreased from 0.97 (95 % CI:0.93-0.99) to 0.80 (95 % CI:0.69-0.89), and PPV decreased from 0.96 (95 % CI:0.92-0.99) to 0.84 (95 % CI:0.73-0.92). Multivariate analysis found age, EV-A71 vaccination, previous HFMD/Herpangina infection, disease severity, infection during peak EV-A71 season, and sampling time after symptom onset were significantly associated with the diagnostic performance of this anti-EV-A71 IgM-capture ELISA. CONCLUSION: Achieving satisfactory specificity and sensitivity scores, this commercial anti-EV-A71 IgM-capture ELISA kit is suitable for clinical EV-A71 diagnosis, particularly in resource-poor areas. However, clinicians should interpret results in the context of patient history and epidemiological setting.

Sulfosalicylic acid/Fe3+ based nanoscale coordination polymers for effective cancer therapy by the Fenton reaction: an inspiration for understanding the role of aspirin in the prevention of cancer.

Fenton reaction-based reactive oxygen species (ROS) generation provides a new idea for the design of ROS-mediated anticancer agents. Finding ways to increase iron uptake and to elevate the level of H2O2 in cells simultaneously is thus crucial to this strategy. Meanwhile, salicylic acid (SA) or its analogue, as the major metabolite of aspirin, has been reported to be closely associated with an intracellular redox-active product. In this work, a PEG-modified nanoscale coordination polymer (PFNC) via the self-assembly of 5-sulfosalicylic acid (SSA) with Fe3+ ions has been designed for the first time. The results show that the SSA dissociated from the PFNC can lead to the decrease of GSH and the accumulation of H2O2 in cancer cells, and thus elevate cellular ROS via the Fenton reaction. Owing to such intracellular oxidative stress, PFNC-induced ferroptotic cell death was further confirmed. In vitro cytotoxicity studies show that PFNCs display higher cytotoxicity on cancer cells than on normal cells. In vivo experiments further demonstrate that PFNCs not only possess high tumor accumulation, but also significantly inhibit the tumor growth without obvious damage toward the major organs. Based on the results, we expect that this work will provide an inspiration for understanding the role of SA, even aspirin, in the prevention of cancer.

Biodegradable Polymer Microparticles with Tunable Shapes and Surface Textures for Enhancement of Dendritic Cell Maturation.

In this report, we present a facile approach to produce biodegradable polymeric microparticles with uniform sizes and controllable morphologies by blending hydrophobic poly(d, l-lactic-co-glycolide) (PLGA) and amphiphilic poly(d, l-lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG) in a microfluidic chip. Microparticles with tentacular, hollow hemispherical, and Janus structures were obtained after complete evaporation of the organic solvent by manipulating the interfacial behavior of emulsion droplets and the phase separation behavior inside the droplets. The number and length of the tentacles on the surface of tentacular microparticles could be tailored by varying the initial concentration and blending ratios of the polymers. The organic solvent played an important role in controlling the morphologies of microparticles. For example, blending PLA16k-b-PEG5k with PLGA100k in dichloromethane resulted in tentacular microparticles, whereas hollow hemispherical microparticles were obtained in trichloromethane. Moreover, these microparticles with controllable shapes and surface textures have significant influence on the immune response of dendritic cells (DCs), showing a morphology-dependent enhancement of DC maturation.

Polyethylenimine Hybrid Thin-Shell Hollow Mesoporous Silica Nanoparticles as Vaccine Self-Adjuvants for Cancer Immunotherapy.

Conventional adjuvants (e.g., aluminum) are insufficient to trigger cell-mediated immunity, which plays a crucial role in triggering specific immunity against cancer. Therefore, developing appropriate adjuvants for cancer vaccines is a central way to stimulate the antitumor immune response. Hollow mesoporous silica nanoparticles (HMSNs) have been proven to stimulate Th1 antitumor immunity in vivo and promote immunological memory in the formulation of novel cancer vaccines. Yet, immune response rates of existing HMSNs for anticancer immunity still remain low. Here, we demonstrate the generation of polyethylenimine (PEI)-incorporated thin-shell HMSNs (THMSNs) through a facile PEI etching strategy for cancer immunotherapy. Interestingly, incorporation of PEI and thin-shell hollow structures of THMSNs not only improved the antigen-loading efficacy and sustained drug release profiles but also enhanced the phagocytosis efficiency by dendritic cells (DCs), enabled DC maturation and Th1 immunity, and sustained immunological memory, resulting in the enhancement of the adjuvant effect of THMSNs. Moreover, THMSNs vaccines without significant side effects can significantly reduce the potentiality of tumor growth and metastasis in tumor challenge and rechallenge models, respectively. THMSNs are considered to be promising vehicles and excellent adjuvants for the formulation of cancer vaccines for immunotherapy.

Function and mechanism of mesoporous bioactive glass adsorbed epidermal growth factor for accelerating bone tissue regeneration.

Mesoporous bioactive glass (MBG) has been demonstrated to play a vital role in bone tissue engineering due to its bioactivity, biocompatibility, and osteoinduction properties. Here, we report that MBG grafted with an amino group (MBG-NH2) and MBG-NH2 adsorbed epidermal growth factor (EGF) (MBG-NH2/EGF) sustained-release EGF, and MBG-NH2/EGF could accelerate osteoblast differentiation and mineralization in MC3T3-E1 cells. We found that MBG-NH2 could promote bone-like deposit formation and Ca deposition in vitro. Intriguingly, we observed that MBG-NH2/EGF enhanced MC3T3-E1 cell adhesion. We also showed that extracellular signal-regulated kinase 1/2 (ERK1/2) was phosphorylated when MC3T3-E1 cells were cultured on MBG-NH2/EGF. Interestingly, the transcription factor Runx2, important for osteoblast differentiation, was also activated when MC3T3-E1 cells were cultured on MBG-NH2/EGF. We showed that MC3T3-E1 cells cultured on MBG-NH2/EGF activating Runx2 was through ERK1/2 phosphorylation. Consistent with this survey, we observed that MC3T3-E1 cells cultured on MBG-NH2/EGF accelerated osteoblastic marker gene expressions, including osteopontin (Opn) and osteocalcin (Ocn). Taken together, we conclude that the osteoblast differentiation and mineralization were accelerated in MC3T3-E1 cells cultured on MBG-NH2/EGF through ERK-activated Runx2 pathway. These findings support the idea that MBG-NH2/EGF is a potential biomaterial for bone tissue repair in bone defect-related diseases.