Industrially Scalable Approach to Nanohybrid Shish Kebabs by In Situ Nanofibrillation of Isotactic Poly(propylene)

Herein, a feasible protocol of nanohybrid shish kebab (NHSK) in isotactic poly(propylene) (iPP)/low density polyethylene (LDPE) blend is shown, where iPP nanofibrils in situ generate during melt compounding followed by hot stretching, thus serving as shish to induce the kebabs of LDPE under extensional flow, therewith leading to greatly improved mechanical properties. Although scanning electron microscope and small angle X‐ray scattering results reveal classic characteristic of NHSK, wide angle X‐ray diffraction demonstrates that some LDPE chains within the kebabs of LDPE are actually tilted off the flow direction. Through the comparison of LDPE lamellae epitaxially growing on iPP nanofibrils substrate under quiescent condition, it is concluded that the extensional flow affects the formation of NHSK notably, mainly by enhancing nuclei density and further influencing the twist of LDPE lamellae. Moreover, of particular significance is the methodology based on practical processing of extrusion in this work, making it promising to industrially achieve NHSK in polymer blend with advanced performance.

     

Effect of the addition of functionalized TiO2 nanotubes and nanoparticles on properties of experimental resin composites

ObjectiveTo evaluate the influence of the addition of functionalized and non-functionalized TiO₂ nanostructures on properties of a resin composite.MethodsTiO₂ nanostructures were synthesized and functionalized, using 3-(aminopropyl)triethoxysilane (APTMS) and 3-(trimethoxysilyl)propyl methacrylate (TSMPM). Characterizations were performed with XRD, EDS, TEM, and TGA. Resin composites containing Bis-GMA/TEGDMA, CQ, DABE, and barium-aluminum silicate glass were produced according to TiO₂ nanostructure (nanotube or nanoparticle), concentration (0.3 or 0.9 wt%), and functionalization (APTMS or TSMPM). The resin composite without nanostructures was used as control. The amount of fillers was kept constant at 78.3 wt% for all materials. The degree of conversion (DC - at 0 h and 24 h), maximum polymerization rate (Rp_max), and Knoop microhardness (KHN before and after ethanol softening) were evaluated. Data were analyzed with two-way ANOVA with repeated measures and Tukey's HSD (α = 0.05).ResultsTGA results demonstrated that functionalizations were effective for both nanostructures. For DC, resin composites, time and interaction effect were significant (p < 0.001). Higher DC was found for 0.3-wt%-functionalized-nanotubes at 24 h. For nanoparticles, only 0.9-wt%-non-functionalized and 0.3-wt%-APTMS-functionalized showed DC similar to the control and all other groups showed higher DC (p < 0.05). Rp_max was higher for 0.3-wt%-APTMS-nanotubes, which corresponded to higher DC after 24 h. The lowest Rp_max occurred for 0.9-wt%-TSMPM-nanotubes, which showed smaller DC at 0 h. For KHN, resin composites, ethanol softening and interaction effect were significant (p < 0.001). KHN decreased after ethanol softening all groups, except for 0.3-wt%-TSMPM-nanotubes, 0.9-wt%-TSMPM-nanotubes, and 0.3-wt%-non-functionalized-nanoparticles.ConclusionThe resin with 0.3-wt%-TSMPM-nanotubes showed higher DC after 24 h, while being the most stable material after the ethanol softening.SignificanceThe addition of functionalized TiO₂ nanostructures in resin-based materials may improve the properties of the material.     

Stem cell differentiation and human liver disease

Human stem cells are scalable cell populations capable of cellular differentiation. This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells. Such an approach has the potential to improve our understanding of human biology and treating disease. In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases. In recent years, efficient hepatic differentiation from human stem cells has been achieved by several research groups including our own. In this review we provide an overview of the field and discuss the future potential and limitations of stem cell technology.     

Differential intra-endothelial delivery of polymer nanocarriers targeted to distinct PECAM-1 epitopes

Coupling drug carriers to antibodies for targeting endothelial cells (ECs) may improve treatment of vascular and pulmonary diseases. Selecting antibodies that deliver carriers to the cell surface or intracellularly may further optimize specificity of interventions. We studied antibody-directed targeting of nanocarriers to platelet–endothelial cell adhesion molecule (PECAM)-1, an endothelial glycoprotein containing 6 Ig-like extracellular domains. PECAM-1 antibodies bind to ECs without internalization, but ECs internalize by endocytosis nanocarriers carrying multiple copies of anti-PECAM (anti-PECAM/NCs). To determine whether binding and intracellular transport of anti-PECAM/NCs depend on the epitope engaged, we targeted five PECAM-1 epitopes: mAb35, mAb37 and mAb62 (membrane-distal Ig domain 1), mAbGi34 (Ig domains 2/3), and mAb4G6 (membrane-proximal Ig domain 6). The antibodies bound to ECs regardless of the epitope proximity to the plasmalemma, whereas 130 nm diameter nanocarriers only targeted effectively distal domains (mAb4G6/NCs did not bind to ECs). ECs internalized mAb35, mAb62, and mAbGi34 carriers regardless of their size (0.13 to 5 μm diameter), yet they did not internalize mAb37/NCs. After internalization, mAb62/NCs trafficked to lysosomes within 2–3 h, whereas mAb35/NCs had prolonged residence in pre-lysosomal vesicles. Therefore, endothelial binding, endocytosis, and intracellular transport of anti-PECAM/NCs are epitope-specific. This paradigm will guide the design of endothelial drug delivery systems providing specific cellular localizations.     

Intraperitoneal administration of novel doxorubicin loaded polymeric delivery systems against peritoneal carcinomatosis: experimental study in a murine model of ovarian cancer

Objective

Peritoneal spread is an adverse outcome in ovarian cancer. Despite clinical efficiency, intraperitoneal (i.p.) chemotherapy after cytoreductive surgery is associated with high systemic and local toxicity. Two polymer-drug delivery systems (P-HYD1-DOX and P-HYD2-DOX) were developed for i.p. administration by conjugating doxorubicin (DOX) to a poly(l-Lysine citramide) polymer carrier with a hydrazone-based degradable spacer. The aim of this study was to assess the antitumoral efficacy of these two conjugates in a xenograft model of human ovarian carcinomatosis.

Methods

Peritoneal carcinomatosis was generated in athymic mice by i.p. injection of SKOV3-Luc cells. Free DOX, P-HYD1-DOX and P-HYD2-DOX solutions were administered i.p. at the same dose of 10 mg/kg (DOX eq.). For each treatment, tumor load and therapeutic efficacy were compared to untreated mice and assessed by bioluminescence imaging and survival rates. Toxicity profiles in each group and biodistribution of P-HYD2-DOX after i.p. administration were also determined.

Results

P-HYD-1-DOX and P-HYD-2-DOX demonstrated significant antitumoral efficacy against peritoneal carcinomatosis. Compared to untreated group, P-HYD1-DOX improved median survival times from 58 to 105 days. For P-HYD2-DOX, median survival was not reached after a follow-up of 120 days. Bioluminescence showed high efficacy of P-HYD-2-DOX compared to free DOX but the difference was not significant. Biodistribution study confirmed that free and active DOX were successively released from P-HYD2-DOX in vivo. P-HYD-DOX conjugates were well tolerated by mice after i.p. injection.

Conclusion

P-HYD-DOX conjugates demonstrated significant activity against peritoneal carcinomatosis in a xenograft model of ovarian carcinomatosis and their ability to release active DOX in i.p. deposits and tumor. These features are of clinical interest for i.p. administration in the treatment of ovarian peritoneal carcinomatosis after cytoreductive surgery.     

Bending moment of implants restored with CAD/CAM polymer-based restoration materials with or without a titanium base before and after artificial aging

ObjectivesTo test and compare two types of implant systems restored with four monolithic polymer-based materials with regard to their bending moments (BM) before and after aging.MethodsA total of 192 tissue-level implants (TRI Dental Implants) differing in the presence (TiB, Octa line, n = 96) or absence (NTiB, Matrix line, n = 96) of a titanium base were restored with mandibular right first molar crowns manufactured from composite (CC), polymer-infiltrated ceramic (VE), PMMA (PM) and a 3D printed resin (ND) (n = 24). Half of the specimens (n = 12) were loaded for 1,200,000 cycles (50 N, 1.3 Hz, TC: 5/55 °C, 6000×) and examined for failures. Fracture load was measured according to ISO standard 14801, BM was calculated, and fracture types were examined. Data were analyzed using parametric statistics (p < 0.05).ResultsNo failures were observed after 600,000 cycles. After 1,200,000 cycles, wear traces were recorded in all groups except PM, VE and CC on TiB implants. In group CC on NTiB implants, three specimens were rated zero in BM testing as they showed fracture of the screw. Regarding BM, TiB implants exhibited higher values than NTiB implants with aged CC (p = 0.023), aged PM (p < 0.001), initial PM (p = 0.011) and initial VE (p < 0.001). No differences occurred among the implant types with initial CC, initial ND, aged ND and aged VE. With regard to initial BM values, NTiB implants showed higher values for ND and CC compared with PM and VE (p < 0.001). No differences in initial BM values were found for the tested materials on TiB implants (p > 0.116). When aged, restoration material had no impact on the BM values of NTiB implants (p ≥ 0.233). Aged TiB implants showed higher values in combination with CC than with ND (p = 0.001). PM and VE showed similar values as ND and CC. Artificial aging led to a decrease of BM within PM, CC and ND on NTiB implants and ND on TiB implants. The majority of failures after testing were characterized by crown fractures in two to four pieces. Fractures in more pieces with smaller fragments occurred primarily for ND.SignificanceThe use of NTiB implants with the polymer-based materials tested can only be recommended for clinical use as interim prostheses. CC seems to show a positive effect on the BM. Clinical research investigating the in vivo behavior is necessary to confirm these findings.     

Synthesis and swelling properties of novel pH-sensitive poly(aspartic acid) gels

Chemically cross-linked poly(aspartic acid) (PASP) gels were prepared by the hydrolysis of poly(succinimide) (PSI). The latter was prepared by thermal polycondensation of aspartic acid. The PSI chains were cross-linked by natural amines and amino acid derivatives such as putrescin, spermine, spermidine, lysine and cystamine to obtain biodegradable, biocompatible, amino acid-based hydrogels. The volume of the synthesized unhydrolyzed PSI gels changes abruptly at a well-defined pH that results in ring opening, while the hydrolyzed gels show a volume phase transition around the pK values of PASP. The unidirectional stress–strain behavior of the gels as well as the dependence of equilibrium swelling degree on the pH was carefully studied and the most important network parameters were determined by a modified version of the Brannon–Peppas–Peppas theory.     

Dynamic mechanical behavior of starch-based scaffolds in dry and physiologically simulated conditions: effect of porosity and pore size

The three-dimensional scaffolds of a blend of starch and poly(L-lactic) acid, SPLA70, were produced using compression molding of polymer/salt mixture followed by leaching of salt. One series of scaffolds were prepared with varying polymer-to-salt ratio while keeping the salt size constant, and the other series of scaffolds were prepared with varying salt sizes while keeping the polymer-to-salt ratio constant. The X-ray microcomputed tomography and scanning electron microscopy assay were used to analyze the porous morphologies, porosity and distribution of porosity of the porous scaffolds. Salt-free and integrated SPLA70 scaffolds with porosities ranging from 74% to 82% and pore sizes of 125-250 to 500-1000 microm can be fabricated using the present fabrication technique. The water uptake of the SPLA70 scaffolds increases with increasing porosities and also with increasing pore size. In dry state, the storage modulus decreases with increasing porosity and also with increasing pore size. The normalized modulus values are related to normalized density of the scaffolds by a power-law function with an exponent between 2 and 3. For the immersed scaffolds under physiological conditions, the storage modulus was less dependent on porosity and pore size. However, the loss factor increased significantly compared with dry state measurements. The present study clearly shows that the mechanical performance of porous polymeric constructs in dry and in immersed state is completely different, and for comparison with biomechanical performance of tissues, the tests should ideally be performed in immersed state.     

pH敏感的肿瘤靶向聚合物胶束的体外性质

目的 制备肿瘤微环境敏感、具有肿瘤细胞靶向能力和穿膜能力的融合肽FQSIYPpIKRRRRRRRRHHHHC (FRH)修饰的聚合物胶束,并对其体外性质进行初步考察.方法 采用FRH修饰N-(2-羟丙基)-甲基丙烯酰胺(HPMA)聚合物-β-谷甾醇(β-SITO),形成HPMA聚合物胶束(FRH-M),考察其理化性质、肿瘤细胞的摄取和抑制肿瘤细胞生长的效果.结果 透射电镜显示:胶束为均匀的类球形.FRH-M胶束粒径约为55 nm,阿霉素载药量8.3％.该胶束在pH7.4条件下,Zeta电位为-3.01±0.05 mV,在pH6.4条件下,电荷翻转为5.27-0.32 mV.FRH-M的药物释放速度随释放介质的pH降低而加快.FRH-M的细胞摄取较未经修饰胶束的P-M提升了1.9倍;且在pH6.4条件下的细胞摄取明显高于pH7.4的,FRH-M的IC50值为1.40 ±0.41 μg·mL-1,明显低于未经配体修饰的胶束(5.08±0.33 μg· mL-1).结论 经FRH多肽修饰的聚合物胶束具有良好的肿瘤微环境响应能力,且有更好的细胞摄取能力和体外抗肿瘤活性,极具发展前景.     

三氧化物聚合体用于穿孔修补和根尖屏障的疗效分析

目的:研究无机三氧化物聚合体(MTA)运用于穿孔修补和根尖屏障的临床治疗效果。方法:选取我院收治的根管穿孔或根尖敞开患者52例,根据单双数原则,分为参照组和研究组各26例,两组患者均进行穿孔修补和根尖屏障。参照组患者给予氢氧化钙糊剂填充,研究组给予三氧化物聚合体填充。比较两组3m、6m后的临床治疗效果和疼痛发生情况。结果:患者治疗3个月后及治疗6个月后,研究组患者临床治疗有效率均明显高于参照组(P<0.05);研究组疼痛发生情况也明显优于参照组(P<0.05)。结论:三氧化物聚合体是一种良好的牙体填充材料,应用此材料填充的穿孔修补及根尖屏障,有效的改善了患者的疼痛情况,其效果显著。