Injectable Ovalbumin-Based Composite Implant for Photothermal Tumor Therapy.

Polymeric hydrogels with three-dimensional network structures have found tremendous applications in biomedicine. Herein, we report the synthesis of a multifunctional implant based on ovalbumin (OVA) as a carrier capable of synergistically delivering a photothermal transducing agent (polydopamine, PDA) to tumors. The formation of PDA was achieved by utilizing the basicity of OVA, whereas the formation of the hydrogel implant was achieved through the in vitro/in vivo near-infrared (NIR) laser-induced hyperthermia of PDA. The as-prepared PDA@OVA implant exhibits high photothermal conversion efficiency (38.7 %). Once implanted in vivo, the OVA-based implant shows great versatility in the treatment of malignant tumors. Furthermore, a chemotherapeutic (doxorubicin, DOX) and a contrast agent (iohexol), dispersed in the OVA solution in advance, can also be firmly entrapped in the hydrogel along with the hydrogel formation. It is anticipated that the multifunctional OVA-based implant, not showing any obvious toxicity to healthy tissue, could be a promising system for synergistic cancer treatment.

Injectable polyamide-amine dendrimer-crosslinked meloxicam-containing poly-γ-glutamic acid hydrogel for prevention of postoperative tissue adhesion through inhibiting inflammatory responses and balancing the fibrinolytic system.

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from âˆ¼ 57.31 kPa to âˆ¼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of âˆ¼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.

Development of PVA-based microsphere as a potential embolization agent.

The development of tissue adhesive embolization microspheres with imaging ability is one of the important methods to improve the efficacy of interventional embolization. This study reported the synthesis of iodine (I)-polyvinyl alcohol (PVA)@polydopamine (PDA) microspheres to achieve the computed tomography image, drug loading and controlled release, and the enhanced embolization of liver portal vein. The I-PVA@PDA microspheres with a diameter of 147.9 µm showed an excellent computed tomography imaging ability. Moreover, the introduction of PDA endowed the I-PVA@PDA microspheres with tissue adhesive ability and therefore the in vivo embolization effect was improved. The in vivo embolization results showed that focal necrosis of hepatocytes with necrotic cell fragments and inflammatory cell infiltration was observed in the liver tissue, proving that the I-PVA@PDA microspheres have an enhanced embolization effect than PVA particles. The I-PVA@PDA microspheres were further used to deliver and release of chemotherapeutic drugs (5-fluorouracil), which displayed an initial fast release (release amount: 29.74%) in the first 24 h and then a sustained release of 34.48% within 72 h. Moreover, as a universal platform, the PVA@PDA microspheres could combine with other imaging agents like Bi2S3, thus holding a great potential in the interventional treatment of different diseases.

Pooled Analysis of Gastric Emptying in Patients With Obesity: Implications for Oral Absorption Projection.

PURPOSE: Gastric emptying time is one of limiting factors that determines the pharmacokinetic properties of drugs administered by mouth. Despite the high prevalence of obesity worldwide, modifications in gastric emptying time have not been systematically addressed in this set of patients. The current analysis aims to quantitatively address obesity-related changes in gastric emptying time of solids, semisolids, and liquids compared with lean individuals, highlighting the relevant pharmacokinetic implications of oral drug absorption in patients with obesity. METHODS: We searched the Cochrane Library, PubMed, Web of Science, and Embase for all relevant articles published until November 1, 2020. Differences in gastrointestinal variables in relation to gastric emptying between obese and lean individuals were quantified by weighted mean difference (WMD) and ratio of means (RoM). Robustness of the analyses was evaluated by subgroup analysis and publication bias test. FINDINGS: A total of 17 studies with 906 participants were included. The gastric half-emptying time of solids (WMD, -10.4 minutes; P = 0.001; RoM, 0.90; P = 0.01) and liquids (WMD, -6.14 minutes; P < 0.001; RoM, 0.83, P = 0.03) was significantly shorter in individuals with obesity compared with lean individuals. These findings were confirmed by the subgroup analyses and publication bias tests. IMPLICATIONS: Our pooled analysis systemically quantifies the differences in gastric half-emptying time between individuals with obesity and lean individuals, facilitating better understanding and prediction of drug absorption in individuals with obesity through physiologically based pharmacokinetic approaches. Obesity is associated with a faster transit of both solids and liquids through the stomach.

Preparation of Poly(lactic-co-glycolic acid)-Based Composite Microfibers for Postoperative Treatment of Tumor in NIR I and NIR II Biowindows.

In this work, a novel kind of electrospun microfiber to deliver a photothermal agent and an anticancer drug to tumor sites is explored. Photothermal therapy agent (MoS2 nanosheets) and doxorubicin (DOX) are incorporated with poly(lactic-co-glycolic acid) (PLGA) microfiber via electrospinning a solution of PLGA, MoS2 , and DOX. The designed microfiber with uniform fibrous morphology and negligible in vitro/in vivo hemo-/histo-toxicity is used as a durable photothermal agent, which shows an excellent photothermal transform ability and acceptable photothermal stability in both the first and second near-infrared light (NIR I and II) biowindows. The synergistic in vivo tumor chemotherapy and photothermal therapy efficiency of the composite microfibers are studied in postoperative treatment of cancer. It is found that the tumor postoperative reoccurrence can be completely prohibited owing to the synergistic tumor therapy efficiency in both the NIR I and NIR II biowindows.

[Fabrication and accuracy research on 3D printing dental model based on cone beam computed tomography digital modeling].

OBJECTIVE: The aim of this study is to build a digital dental model with cone beam computed tomography (CBCT), to fabricate a virtual model via 3D printing, and to determine the accuracy of 3D printing dental model by comparing the result with a traditional dental cast. METHODS: CBCT of orthodontic patients was obtained to build a digital dental model by using Mimics 10.01 and Geomagic studio software. The 3D virtual models were fabricated via fused deposition modeling technique (FDM). The 3D virtual models were compared with the traditional cast models by using a Vernier caliper. The measurements used for comparison included the width of each tooth, the length and width of the maxillary and mandibular arches, and the length of the posterior dental crest. RESULTS: 3D printing models had higher accuracy compared with the traditional cast models. The results of the paired t-test of all data showed that no statistically significant difference was observed between the two groups (P>0.05). CONCLUSIONS: Dental digital models built with CBCT realize the digital storage of patients' dental condition. The virtual dental model fabricated via 3D printing avoids traditional impression and simplifies the clinical examination process. The 3D printing dental models produced via FDM show a high degree of accuracy. Thus, these models are appropriate for clinical practice.

Synergistic thermoradiotherapy based on PEGylated Cu3BiS3 ternary semiconductor nanorods with strong absorption in the second near-infrared window.

In this work, we report a successful synthesis of copper bismuth sulfide nanorods (NRs) with broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, which can be used as a 1064 nm-laser-driven photothermal agent with the photothermal conversion efficiency of 40.7%, noticeably higher than most of the reported PTT agents working in NIR-II window. The as-prepared PEGylated Cu3BiS3 NRs were used as photoacoustic imaging (PAI) and CT imaging agents due to their strong NIR absorption and large X-ray attenuation coefficient of bismuth. We are the first to demonstrate that a small quantity of PEGylated Cu3BiS3 NRs in tumors can concentrate radiation energy and trigger mild PTT under NIR-II irradiation and thus, these particles could be used as a novel, synergistic thermoradiotheraputic agent that enhances the efficacy of radiotherapy.

3D Poly(Lactic-co-glycolic acid) Scaffolds for Treating Spinal Cord Injury.

In this paper, poly(lactic-co-glycolic acid) (PLGA) was used to fabricate spinal cord scaffolds using low temperature deposition manufacturing (LDM) technology. The PLGA scaffolds were characterized as having good porosity, hydrophilicity and considerable biodegradability. The effects of the PLGA scaffolds on cell proliferation and cytotoxicity were evaluated by culturing Schwann cells (SCs) on the surfaces of the scaffolds. The results showed that the SCs spread and proliferated well on the PLGA scaffolds. Histological assessment including Glia fibrillary acidic protein (GFAP) staining, Nissl staining, Luxol fast blue (LFB) staining and Bielschowsky silver staining showed that the spinal cord recoveries considerably improved with the PLGA scaffolds, indicating that the PLGA scaffolds exhibited potential for applications in the management of spinal cord injuries.

Self-assembled microbubbles as contrast agents for ultrasound/magnetic resonance dual-modality imaging.

In this work, superparamagnetic self-assembled microbubbles (SAMBs) consisting of "Poly(acrylic acid)-Iron oxide nanoparticles-Polyamine" sandwich-like shells and tetradecafluorohexane cores were fabricated by a template-free self-assembly approach. The SAMBs exhibit not only magnetic resonance (MR) T2 imaging functionality, but also ultrasound (US) image contrast, showing great potential as US/MR dual contrast agents. The diameters of the SAMBs can be tuned easily from 450nm to 1300nm by changing the precursor ratio, and this size variation directly affects their in vitro MRI and US signals. The SAMBs also exhibit in vivo contrast enhancement capabilities in rat liver with injection through portal vein, for both MR and US imaging. Additionally, the biodistribution of SAMBs over time suggests normal systemic metabolic activity through the spleen. The results show that the Fe content in rat liver reduces to a level of which Fe cannot be detected in 45days. The SAMBs exhibit no obvious damage to the primary organs of rat during the metabolic process, indicating their good biocompatibility in vivo.

A Facile One-Pot Synthesis of a Two-Dimensional MoS2 /Bi2S3 Composite Theranostic Nanosystem for Multi-Modality Tumor Imaging and Therapy.

2D PEG-ylated MoS2/Bi2 S3 composite nanosheets are successfully constructed by introducing bismuth ions to react with the two extra S atoms in a (NH4)2 MoS4 molecule precursor for solvothermal synthesis of MoS2. The MBP nanosheets can serve as a promising platform for computed tomography and photoacoustic-imaging-guided tumor diagnosis, as well as combined tumor photothermal therapy and sensitized radiotherapy.

Delivering mesenchymal stem cells in collagen microsphere carriers to rabbit degenerative disc: reduced risk of osteophyte formation.

Mesenchymal stem cells (MSCs) have the potential to treat early intervertebral disc (IVD) degeneration. However, during intradiscal injection, the vast majority of cells leaked out even in the presence of hydrogel carrier. Recent evidence suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, an undesirable side effect. This suggests the significance of developing appropriate carriers for intradiscal delivery of MSCs. We previously developed a collagen microencapsulation platform, which entraps MSCs in a solid microsphere consisting of collagen nanofiber meshwork. These solid yet porous microspheres support MSC attachment, survival, proliferation, migration, differentiation, and matrix remodeling. Here we hypothesize that intradiscal injection of MSCs in collagen microspheres will outperform that of MSCs in saline in terms of better functional outcomes and reduced side effects. Specifically, we induced disc degeneration in rabbits and then intradiscally injected autologous MSCs, either packaged within collagen microspheres or directly suspended in saline, into different disc levels. Functional outcomes including hydration index and disc height were monitored regularly until 6 months. Upon sacrifice, the involved discs were harvested for histological, biochemical, and biomechanical evaluations. MSCs in collagen microspheres showed advantage over MSCs in saline in better maintaining the dynamic mechanical behavior but similar performance in hydration and disc height maintenance and matrix composition. More importantly, upon examination of gross appearance, radiograph, and histology of IVD, delivering MSCs in collagen microspheres significantly reduced the risk of osteophyte formation as compared to that in saline. This work demonstrates the significance of using cell carriers during intradiscal injection of MSCs in treating disc degeneration.

Multifunctional PEGylated multiwalled carbon nanotubes for enhanced blood pool and tumor MR imaging.

Long-circulating multifunctional Gd(III)-loaded multiwalled carbon nanotubes (MWCNTs) modified with polyethylene glycol are designed and synthesized. The formed MWCNTs are water-dispersible, stable, and have good cytocompatibility and antifouling property. With the low r 2 /r 1 relaxivity ratio and relatively long blood circulation time, the multifunctional MWCNTs are able to be used as a platform for enhanced blood pool and tumor MR imaging.

Facile hydrothermal synthesis and surface functionalization of polyethyleneimine-coated iron oxide nanoparticles for biomedical applications.

We report the facile hydrothermal synthesis and surface functionalization of branched polyethyleneimine (PEI)-coated iron oxide nanoparticles (Fe3O4-PEI NPs) for biomedical applications. In this study, Fe3O4-PEI NPs were synthesized via a one-pot hydrothermal method in the presence of PEI. The formed Fe3O4-PEI NPs with primary amine groups on the surface were able to be further functionalized with polyethylene glycol (PEG), acetic anhydride, and succinic anhydride, respectively. The formed pristine and functionalized Fe3O4-PEI NPs were characterized via different techniques. We showed that the sizes of the Fe3O4-PEI NPs were able to be controlled by varying the mass ratio of Fe(II) salt and PEI. In addition, the formed Fe3O4-PEI NPs with different surface functionalities had good water dispersibility, colloidal stability, and relatively high R2 relaxivity (130-160 1/(mM·s)). Cell viability assay data revealed that the surface PEGylation and acylation of Fe3O4-PEI NPs rendered them with good biocompatibility in the given concentration range, while the pristine aminated Fe3O4-PEI NPs started to display slight toxicity at the concentration of 50 µg/mL. Importantly, macrophage cellular uptake results demonstrated that both PEGylation and acetylation of Fe3O4-PEI NPs were able to significantly reduce the nonspecific macrophage uptake, likely rendering the particles with prolonged circulation time. With the proven hemocompatibility and rich amine conjugation chemistry, the Fe3O4-PEI NPs with different surface functionalities may be applied for various biomedical applications, especially for magnetic resonance imaging and therapy.

[Effect of extra-cellular polymeric substances on filtration of modified non-woven fabric in membrane bio-reactor].

The effect of extra-cellular polymeric substances (EPS) on filtration of polyvinyl alcohol modified polypropylene non-woven in submerged membrane bioreactor (SMBR) was investigated by statistical method. The results show that soluble extra-cellular polymeric substances (EPSs) of activated sludge on the non-woven modules surface, components (protein/carbohydrate, P/C) of EPSs and relative hydrophobicity (RH) have a significant influence on filtration performance of module B, the Pearson's correlation coefficient (r(p)) related to membrane fouling resistance are 0.868, 0.840, 0.890, respectively. Modified module can effectively restrict the adsorption of EPSs, can reduce the ratio of P/C in EPSs and can decrease the accumulation of activated sludge. After hydrophilic modification of non-woven, the filtration performance is improved obviously and the un-fouling performance is increased.