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Hepatocellular carcinoma (HCC) is one of the major cancers with high mortality rate. Traditional drugs used in clinic are usually limited by the drug resistance and side effect and novel agents are still needed. Macrolide brefeldin A (BFA) is a well-known lead compound in cancer chemotherapy, however, with poor solubility and instability. In this study, to overcome these disadvantages, BFA was encapsulated in mixed nanomicelles based on TPGS and F127 copolymers (M-BFA). M-BFA was conferred high solubility, colloidal stability, and capability of sustained release of intact BFA. In vitro, M-BFA markedly inhibited the proliferation, induced G0/G1 phase arrest, and caspase-dependent apoptosis in human liver carcinoma HepG2 cells. Moreover, M-BFA also induced autophagic cell death via Akt/mTOR and ERK pathways. In HepG2 tumor-bearing xenograft mice, indocyanine green (ICG) as a fluorescent probe loaded in M-BFA distributed to the tumor tissue rapidly, prolonged the blood circulation, and improved the tumor accumulation capacity. More importantly, M-BFA (10 mg/kg) dramatically delayed the tumor progression and induced extensive necrosis of the tumor tissues. Taken together, the present work suggests that M-BFA has promising potential in HCC therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Amyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer Disease. In situ identification of early-stage amyloid aggregates in Alzheimer's disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months. A significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with poly(propylene imine) dendrimers with histidine-maltose shell (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating their putative therapeutic properties of in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques., (© 2021. The Author(s).)

Purpose: The study aimed to evaluate the histologic properties and infection resistance of three different mesh materials in a rat model., Methods: Each mesh, in both infectious (n = 96) and non-infectious groups (n = 270), was positioned both in sublay (preperitoneally) and onlay (subcutaneously) locations. Properties of the biological (Surgisis; Cook Surgical), composite, partially resorbing (Vypro II mesh; Ethicon) and non-resorbing (TiMesh; GFE Medizintechnik GmbH) mesh were evaluated and compared. Animals were killed at 7, 21 and 90 days after implantation. The following parameters were evaluated to assess the host response to the mesh material: inflammation, vascularization, fibrosis, collagen formation, Ki67, and a foreign body reaction by granuloma formation (FBG)., Results: Surgisis mesh produced more pronounced inflammation and cell proliferation, and less intense granuloma formation, as well as fibrosis, compared to the other two groups. When the infected materials were examined, we found signs of local infection to be more often present in Surgisis group of animals., Conclusions: In the presence of bacterial contamination, no benefits were observed in the use of the Surgisis prosthesis over the use of TiMesh and Vypro II.

In the present study, low molecular weight poly(propylene carbonate) (PPC, Mn = 3500), a biodegradable liquid polymer easily prepared from carbon dioxide (CO2), was modified into poly(propylene carbonate)diacrylate (PPC-DA) by acylation, and methoxy poly(ethylene glycol) (mPEG) was modified into methoxy poly(ethylene glycol) acrylate (mPEG-A). Using PPC-DA as the dispersant to dissolve hydrophobic doxorubicin (DOX) and the initiator, and with mPEG-A as the co-monomer and polymerisable surfactant, a biodegradable nanodrug with excellent biocompatibility was prepared by shear emulsification polymerization without surfactants or organic solvent residues. The nanodrug can be efficiently endocytosed by tumor cells and can rapidly release doxorubicin triggered by the acidic endosomal pH. As evidenced by experiments in tumor-bearing mice, such a nanodrug is stealthy during blood circulation, and targets tumor sites with high efficiency. Moreover, this nanodrug is more effective and less toxic than free doxorubicin. This study provides a green and versatile approach for preparing biodegradable nanodrugs via a simple and efficient process. Moreover, this study extends the applications of CO2 based polymers in the biomedical field, promoting the development of CO2 polymerization fixation.

Background: Abdominal wall reconstruction in patients presenting with enteric fistulas and mesh infection is challenging. There is a consensus that synthetic mesh must be avoided in infected operations, and the alternatives to using synthetic mesh, such as component separation techniques and biologic mesh, present disappointing results with expressive wound infection and hernia recurrence rates., Methods: A prospective clinical trial designed to evaluate the short- and long-term outcomes of 40 patients submitted to elective abdominal wall repair with synthetic mesh in the dirty-infected setting, and compared to a cohort of 40 patients submitted to clean ventral hernia repairs. Patients in both groups were submitted to a single-staged repair using onlay polypropylene mesh reinforcement., Results: Groups' characteristics were similar. There were 13 (32.5%) surgical site occurrences in the infected mesh (IM) group, compared to 11 (27.5%) in the clean-control (CC) group, p = 0.626. The 30-day surgical site infection rate was 15% for the IM group vs. 10% for the CC cases, p = 0.499. One patient required a complete mesh removal in each group. The mean overall follow-up was 50.2 ± 14.8 months, with 36 patients in the IM group and 38 clean-controls completing a follow-up of 36 months. There was one hernia recurrence (4.2%) in the IM group and no recurrences in the CC group., Conclusion: We demonstrated that using polypropylene mesh in the infected setting presented similar outcomes to clean repairs. The use of synthetic mesh in the onlay position resulted in a safe and durable abdominal wall reconstruction., Trial Registration: Study registered at Plataforma Brasil (plataformabrasil.saude.gov.br), CAAE 30836614.7.0000.0068. Study registered at Clinical Trials (clinicaltrials.gov), Identifier NCT03702153.

Objective: Experimental assessment of the effect of modified and unmodified surgical suture material on abdominal adhesive process., Material and Methods: The study was performed on male rats of the Wistar subpopulation. There were 5 animals in each group. In all animals, midline abdominal incision was followed by suturing the parietal peritoneum with modified and unmodified suture material. All animals were euthanized with carbon dioxide vapors in 14 days after surgery. Macro- and microscopic assessment of severity of abdominal adhesive process was carried out. Two types of preparation of excised complexes 'peritoneum-suture material-adhesion' were applied for histological examination: paraffin sections and embedding in epoxy resin. Specimens were stained by Van Gieson and with methylene blue solution. Histological specimens were examined using Axio Imager A1 light microscope (Zeiss, Germany)., Results: Polypropylene filaments result extensive adhesions occupying about 75% of the area. Adhesions have a dense structure with signs of vascularization. Modification of suture material with solution of polyhydroxybutyrate/hydroxyvalerate and heparin reduce severity of adhesions. The use of modified suture material was followed by adhesions with more loose structure, no signs of vascularization. Adhesions occupied less than 25% of the area. Histological examination of excised complexes 'peritoneum-suture material-adhesion' revealed accumulation of inflammatory cells around the unmodified suture material, while there were no signs of tissue inflammatory process around the modified sutures., Conclusion: Application of polyhydroxybutyrate/hydroxyvalerate and heparin on the surface of surgical sutures is an effective method for prevention of abdominal adhesions.

Purpose: To Compare the extent and intensity of adhesions formed between the intra-abdominal organs and the intraperitoneal implants of polypropylene mesh versus polypropylene/polyglecaprone versus polyester/porcine collagen used for correction of abdominal wall defect in rats., Methods: After the defect in the abdominal wall, thirty Wistar rats were placed in three groups (ten animals each) for intraperitoneal mesh implant: polypropylene group, polypropylene/polyglecaprone group, and polyester/porcine collagen group. The macroscopic evaluation of the extent and intensity of adhesions was performed 21 days after the implant., Results: The polypropylene group had a higher statistically significant impairment due to visceral adhesions (p value = 0.002) and a higher degree of intense adherence in relation to polypropylene/polyglecaprone and polyester/porcine collagen groups (p value<0.001). The polyester/porcine collagen group showed more intense adhesions than the polypropylene/polyglecaprone group (p value=0.035)., Conclusions: The intraperitoneal implantation of polypropylene meshes to correct defects of the abdominal wall caused the appearance of extensive and firm adhesions to intra-abdominal structures. The use of polypropylene/polyglecaprone or polyester/porcine collagen tissue-separating meshes reduces the number and degree of adhesions formed.

Purpose of Review: To review the current clinical management of stress urinary incontinence and pelvic organ prolapse following the adverse complications seen in the use of polypropylene mesh to treat both., Recent Findings: Materials developed for use in abdominal hernia repair have not proven risk-free when used to support pelvic organs particularly when inserted via the vagina. Following unacceptably high levels of severe complications when high-density polypropylene mesh is inserted via the vagina to treat pelvic organ prolapse, reported over the last decade, there is now an agreed consensus between surgeons about surgical approaches and materials, which should be recommended for use in stress urinary incontinence and pelvic organ prolapse., Summary: There is a need for new biomaterials and tissue engineered/regenerative medicine approaches to treat stress urinary incontinence and pelvic organ prolapse. New materials need to be evaluated critically in both preclinical and clinical studies before being adopted into routine clinical use.

Purpose of Review: This review identifies the clinical complications associated with the design of the current polyproplylene mesh materials used for the treatment of stress urinary incontinence and pelvic organ prolapse. Following on from this, new alternative materials under development for pelvic floor repair are reviewed., Recent Findings: It is well accepted that the textile properties of the current polypropylene surgical meshes are not suitable for the pelvic floor environment. This together with the chemical nature of the current mesh leads to complications whenever implanted in the pelvic floor of women. New alternative materials for the repair of the pelvic floor have been developed with properties designed to be more appropriate for the biomechanical requirements and implantation requirements for the pelvic floor to reduce these clinical complications. To support this, these newer materials are being rigorously tested using more appropriate in-vitro regimes and animal models., Summary: This chapter summarizes developments in the design of new materials for pelvic floor repair. These are being subjected to preclinical testing to exclude materials, which might fail to work in this dynamic environment by either showing a poor mechanical match to the requirements of the tissue or by provoking sustained inflammation. The hope is that new materials will prove effective without causing the high incidence of unacceptable side-effects currently seen with polypropylene mesh implants.

Purpose of Review: The present article reviews the history of mesh-related complications and regulations in SUI and POP repair settings, clinical outcomes associated with the use of biologic and synthetic mesh materials, and novel approaches using modified mesh materials., Recent Findings: Treatment of pelvic floor disorders, such as stress urinary incontinence (SUI) and pelvic organ prolapse (POP) commonly involves implantation of synthetic surgical mesh materials like polypropylene. Many synthetic mesh materials, however, are associated with a foreign body response upon implantation, which is characterized by fibrotic encapsulation. Complications, including erosion, infections, bleeding, and chronic pain, have led to warnings by regulatory agencies and the recall of several mesh products. To mitigate such complications, biologic mesh materials have been proposed as alternatives for SUI and POP repair., Summary: Clinical outcomes of surgical repair of POP/SUI are similar between biologic and synthetic meshes, but biologic meshes have a lower incidence of adverse effects. Several strategies for modifying or functionalizing biological and synthetic meshes have shown promising results in preclinical studies.

"The majority of hernias can be satisfactorily repaired by using the tissues at hand. The use of mesh prosthesis should be restricted to those few hernias in which tension or lack of good fascial structures prevents a secure primary repair. This group includes large direct inguinal hernias and incisional hernias in which the defect is too large to close primarily without undue tension. Most recurrent hernias, because of this factor are best repaired with mesh prosthesis". These words, penned in 1960 by Francis Usher have reconfirmed what had been a mantra of the Shouldice Hospital (Usher in 81:847-854, 1960). The Shouldice Hospital has specialized in the treatment of abdominal wall hernias since 1945. It has, since its beginning, insisted on the fact that a thorough knowledge of anatomy coupled with large volumes of surgical cases would lead to unparalleled expertise. It was Cicero who taught us that "Practice, not intelligence or dexterity, will win the day"! Since the seminal contribution of Bassini (1844-1924), there have been no less than 80 procedures imitating his inguinal herniorrhaphy and much more since the introduction of mesh and mesh devices (Iason in Hernia. The Blakiston Company, Philadelphia, pp 475-604, 1940). All have failed to some extent and it appears that the common denominator for these failures was the inability to understand the importance of entering the preperitoneal space. Only Shouldice and McVay (Lotheissen, Narath) realized the shortcoming and have continued to thrive as a successful procedure. Entering the preperitoneal space eliminates any temptation to plicate the posterior inguinal wall, a layer normally deficient in direct inguinal hernias, but it also allows the identification of muscle layers rectus, transversus and internal oblique muscles which will go to reconstruct the posterior inguinal wall, without tension as reported by Schumpelick (Junge in 7(1):17-20, 2003).

Purpose: This study aimed to explore risk factors of postoperative complications for adult patients with incarcerated groin hernia (IGH)., Methods: From January 2010 to December 2017, consecutive patients undergoing emergency hernia repair for IGH in our center were retrospectively reviewed. Postoperative complications, such as surgical site infection, seroma, hernia recurrence and mortality, were investigated, with risk factors for such complications analyzed using univariate and multivariate regressions., Results: Sixty-four patients were included, with 51 males and 13 females (mean age 65.1, range 25-98 years). Ten patients (15.6%) underwent resection of necrotic bowel and anastomosis. 43 patients (67.2%) received open tension-free herniorrhaphy with polypropylene mesh, whereas the rest (32.8%) received herniorrhaphy without mesh. The overall postoperative complication rate was 40.6% (26/64), with an incisional complication rate of 31.2% (20/64) and an infection rate of 6.2% (4/64). At a median follow-up of 32 months, hernia recurrence and mortality were recorded in five cases each (7.8%). Mesh repair was associated with decreased recurrence rate compared with non-mesh repair (2.3% vs. 19.0%, p = 0.019). Diabetes mellitus (OR 8.611, 95%CI 1.292-57.405; p = 0.026) was an independent risk factor of postoperative complications, together with chronic obstructive pulmonary disease (COPD; OR 14.365, 95%CI 1.652-127.767, p = 0.016), intestinal necrosis (OR 14.260, 95%CI 1.079-188.460, p = 0.044), and general anesthesia (OR 14.543, 95%CI 1.682-125.711, p = 0.015) as risk for incisional complications after surgery., Conclusions: Diabetes mellitus was an independent risk factor of postoperative complications for IGH, along with COPD, intestinal necrosis and general anesthesia associated with incisional complications. The use of polypropylene mesh did not increase infection or recurrence rate in this cohort.

The main purpose of the study was to develop valsartan floating tablets (VFT) via non-effervescent technique using low density polypropylene foam powder, carbopol, and xanthan gum by direct compression. Before compression, the particulate powdered mixture was evaluated for pre-compression parameters. The prepared valsartan tablets were evaluated for post-compression parameters, swelling index, floating lag time, in vitro buoyancy studies, and in vitro and in vivo X-ray imaging studies in albino rabbits. The result of all formulations for pre- and post-compression parameters were within the limits of USP. FTIR and DSC studies revealed no interaction between the drug and polymers used. The prepared floating tablets had good swelling and floating capabilities for more than 12 h with zero floating lag time. The release of valsartan from optimized formulation NF-2 showed sustained release up to 12 h; which was found to be non-Fickian release. Moreover, the X-ray imaging of optimized formulation (NF-2) revealed that tablet was constantly floating in the stomach region of the rabbit, thereby indicating improved gastric retention time for more than 12 h. Consequently, all the findings and outcomes have showed that developed valsartan matrix tablets could be effectively used for floating drug delivery system.

Purpose: Synthetic non-absorbable meshes are routinely used in hernia surgery for clean cases but are avoided in the case of clean-contaminated or contaminated hernia or dirty cases to minimize the risk of infection. The present study was conducted to evaluate the outcome of polypropylene mesh in the settings of bowel resection performed for strangulated hernias of the abdominal wall., Methods: This prospective observational study was conducted in the Department of Surgery of a teaching hospital in central India between 1st March 2015 and 31st Aug 2017. Adult patients > 18 years age, with abdominal wall hernias, presenting with strangulation, and requiring resection and anastomosis for gangrenous bowel were included in the study. Outcomes noted were wound infection, morbidity and mortality, need for the removal of the mesh, and recurrence of the hernia., Results: 30 (22 men and 8 women) patients with strangulated hernias underwent emergency surgery with resection of gangrenous bowel and anastomosis. The 30 cases included 21 inguinal, seven incisional, one femoral and one umbilical hernia. 12 of the 30 cases having gross contamination of the operative wound due to perforated gangrenous bowel were classified as 'dirty'; while the remaining 18 cases with non-perforated gangrenous herniating bowel were classified as 'contaminated'. Wound infection occurred in 8/30 patients (26.67%); but these healed with antibiotics and dressing. Mesh removal was not required in any patient during entire study period. Two recurrences (6.7%; one inguinal and one incisional hernia) were observed. There was no mortality., Conclusion: The use of polypropylene mesh for contaminated and dirty strangulated hernias is effective and safe, with acceptable morbidity and good short-term results.

Context: Polypropylenimine (PPI), a cationic dendrimer with defined structure and positive surface charge, is a potent non-viral vector. Dexamethasone (Dexa) conveys to the nucleus through interaction with its intracellular receptor., Objective: This study develops efficient and non-toxic gene carriers through conjugation of Dexa at various percentages (5, 10 and 20%) to the fourth and the fifth generation PPIs (PPIG4s and PPIG5s)., Materials and Methods: The 21-OH group of Dexa (0.536 mmol) was modified with methanesulfonyl chloride (0.644 mmol) to activate it (Dexa-mesylate), and then it was conjugated to PPIs using Traut's reagent. After dialysis (48 h) and lyophilization, the physicochemical characteristics of products (PPI-Dexa) including zeta potential, size, buffering capacity and DNA condensing capability were investigated and compared with unmodified PPIs. Moreover, the cytotoxicity and transfection activity of the Dexa-modified PPIs were assessed using Neuro2A cells., Results: Transfection of PPIG4 was close to PEI 25 kDa. Although the addition of Dexa to PPIG4s did not improve their transfection, their cytotoxicity was improved; especially in the carrier to DNA weight ratios (C/P) of one and two. The Dexa conjugation to PPIG5s enhanced their transfection at C/P ratio of one in both 5% (1.3-fold) and 10% (1.6-fold) Dexa grafting, of which the best result was observed in PPIG5-Dexa 10% at C/P ratio of one., Discussion and Conclusions: The modification of PPIs with Dexa is a promising approach to improve their cytotoxicity and transfection. The higher optimization of physicochemical characteristics, the better cell transfection and toxicity will be achieved.

The possibility of using gene therapy for the treatment of prostate cancer is limited by the lack of intravenously administered delivery systems able to safely and selectively deliver therapeutic genes to tumors. Given that lactoferrin (Lf) receptors are overexpressed on prostate cancer cells, we hypothesized that the conjugation of Lf to generation 3-diaminobutyric polypropylenimine dendrimer would improve its transfection and therapeutic efficacy in prostate cancer cells. In this study, we demonstrated that the intravenous administration of Lf-bearing DAB dendriplexes encoding TNFα resulted in the complete suppression of 70% of PC-3 and 50% of DU145 tumors over one month. Treatment with DAB-Lf dendriplex encoding TRAIL led to tumor suppression of 40% of PC-3 tumors and 20% of DU145 tumors. The treatment was well tolerated by the animals. Lf-bearing generation 3-polypropylenimine dendrimer is therefore a highly promising delivery system for non-viral gene therapy of prostate cancer.

Purpose: To evaluate the fibrosis induced by four different meshes: Marlex®, Parietex Composite®, Vicryl® and Ultrapro®., Methods: Histological cutouts of abdominal wall were analyzed with polarized light 28 days after the meshes implants and colorized by picrosirius to identify the intensity of collagen types I and III, and their maturation index., Results: When the four groups were compared, the total collagen area analyzed was bigger in groups A and D, with no difference between them. The collagen type I density was bigger in group A, with an average of 9.62 ± 1.0, and smaller in group C, with an average of 3.86 ± 0.59. The collagen type III density was similar in groups A, B and C, and bigger in group D. The collagen maturation index was different in each of the four groups, bigger in group A with 0.87, group B with 0.66, group D with 0.57 and group C with 0.33 (p = 0.0000)., Conclusion: The most prominent fibrosis promotion in the given meshes was found on Marlex® (polypropylene mesh) and the Parietex Composite® (non-biodegradable polyester); the collagen maturation index was higher in the Marlex® mesh, followed by Ultrapro®, Parietex Composite® and Vicryl® meshes.

The effect of electron beam radiation on ethylene-propylene diene terpolymer/polypropylene blends is studied as an attempt to develop radiation sterilizable polypropylene/ethylene-propylene diene terpolymer blends suitable for medical devices. The polypropylene/ethylene-propylene diene terpolymer blends with mixing ratios of 80/20, 50/50, 20/80 were prepared in an internal mixer at 165°C and a rotor speed of 50 rpm/min followed by compression molding. The blends and the individual components were radiated using 3.0 MeV electron beam accelerator at doses ranging from 0 to 100 kGy in air and room temperature. All the samples were tested for tensile strength, elongation at break, hardness, impact strength, and morphological properties. After exposing to 25 and 100 kGy radiation doses, 50% PP blend was selected for in vivo studies. Results revealed that radiation-induced crosslinking is dominating in EPDM dominant blends, while radiation-induced degradation is prevailing in PP dominant blends. The 20% PP blend was found to be most compatible for 20-60 kGy radiation sterilization. The retention in impact strength with enhanced tensile strength of 20% PP blend at 20-60 kGy believed to be associated with increased compatibility between PP and EPDM along with the radiation-induced crosslinking. The scanning electron micrographs of the fracture surfaces of the PP/EPDM blends showed evidences consistent with the above contentation. The in vivo studies provide an instinct that the radiated blends are safe to be used for healthcare devices.

Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around -4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100 are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.

Purpose: Fourth-generation poly(propylene imine) dendrimers fully surface-modified by maltose (dense shell, PPI-m DS) were shown to be biocompatible in cellular models, which is important for their application in drug delivery. We decided to verify also their inherent bioactivity, including immunomodulatory activity, for potential clinical applications. We tested their effects on the THP-1 monocytic cell line model of innate immunity effectors., Methods: To estimate the cytotoxicity of dendrimers the reasazurin assay was performed. The expression level of NF-κB targets: IGFBP3, TNFAIP3 and TNF was determined by quantitative real-time RT-PCR. Measurement of NF-κB p65 translocation from cytoplasm to nucleus was conducted with a high-content screening platform and binding of NF-κB to a consensus DNA probe was determined by electrophoretic mobility shift assay. The cytokine assay was performed to measure protein concentration of TNFalpha and IL-4., Results: We found that PPI-m DS did not impact THP-1 viability and growth even at high concentrations (up to 100 μM). They also did not induce expression of genes for important signaling pathways: Jak/STAT, Keap1/Nrf2 and ER stress. However, high concentrations of 4th generation PPI-m DS (25-100 μM), but not their 3rd generation counterparts, induced nuclear translocation of p65 NF-κB protein and its DNA-binding activity, leading to NF-κB-dependent increased expression of mRNA for NF-κB targets: IGFBP3, TNFAIP3 and TNF. However, no increase in pro-inflammatory cytokine secretion was detected., Conclusion: We conclude that maltose-modified PPI dendrimers of specific size could exert a modest immunomodulatory effect, which may be advantageous in clinical applications (e.g. adjuvant effect in anti-cancer vaccines).

Purpose: This study assesses the use of an absorbable polymer loaded with chlorhexidine (CHX) as an antibacterial coating for polypropylene (PP) meshes employed in hernia repair., Methods: The polymer N,N-dimethyl-N-benzyl-N-(2-methacryloyloxyethyl) ammonium bromide was loaded with CHX (1 % w/w). Fragments (1 cm 2 ) of Optilene ® Mesh Elastic were coated either with the unloaded (POL) or CHX-loaded polymer (POL-CHX). Uncoated fragments (PP) served as controls. The release kinetics of the POL-CHX coating was monitored by HPLC. Sterile fragments were placed on agar plates previously contaminated with 10 6  CFU of Staphylococcus aureus (Sa) ATCC25923, Staphylococcus epidermidis (Se) ATCC12228, or Escherichia coli (Ec) ATCC25922 and incubated at 37 °C for 1/2/7 days. At each time point, inhibition halos were measured and bacterial adhesion to the meshes quantified by sonication and scanning electron microscopy. Coating cytotoxic effects were examined on cultured fibroblasts., Results: The polymer coating gradually released CHX over 3 days. Inhibition halos were produced only around the POL-CHX-coated meshes and these were significantly smaller for Ec than Sa or Se (p < 0.01). While POL-CHX prevented bacterial adhesion to the mesh, the reduced bacterial yields over time were observed for the POL-coated versus control PP meshes (p < 0.001). By day 7, only Ec remained attached to the surface of control meshes. The POL coating was not cytotoxic, yet POL-CHX reduced the viability of cultured fibroblasts., Conclusions: When loaded with the antiseptic CHX, this quaternary ammonium-based polymer coating released its contents in a controlled manner indicating its potential prophylactic use to reduce the risk of infection following PP mesh implantation.

Maltose-modified poly(propylene imine) glycodendrimers (PPI-m OS) of the 4th generation provide a promising strategy for leukemia treatment. Anticancer therapy with nucleoside analog drugs such as cytarabine (Ara-C) frequently has limited efficacy due to drug resistance, inefficient uptake and accumulation of the drug inside cancer cells where it has to be transformed into the active triphosphate congener. The cationic nature of PPI dendrimers makes it possible to form complexes with nucleotide Ara-C triphosphate forms (Ara-CTP). The aim of this work was to test the concept of applying PPI glycodendrimers as drug delivery devices in order to facilitate the delivery of activated cytarabine to cancer cells to overcome metabolic limitations of the drug. The study has been carried out using 1301 and HL-60 leukemic cell lines as well as peripheral blood mononuclear cells. The results of cytotoxicity and apoptosis assays showed enhanced activity of Ara-C triphosphate form (Ara-CTP) complexed with PPI-m dendrimers in relation to free Ara-C and Ara-CTP against 1301 leukemic cells. Secondly, enhanced uptake and cytotoxicity of Ara-CTP-dendrimers complexes toward 1301 cells with blocked human equilibrative nucleoside transporter - hENT1 suggested that this combination might be a versatile candidate for chemotherapy against resistant acute lymphoblastic leukemia cells with lower expression of hENT1., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: To compare polypropylene mesh positioned onlay supported by omentum and/or peritoneum versus inlay implantation of polypropylene-based composite mesh in patients with complicated wide-defect ventral hernias., Methods: This was a prospective randomized study carried out on 60 patients presenting with complicated large ventral hernia in the period from January 2012 to January 2016 in the department of Gastrointestinal Surgery unit and Surgical Emergency of the Main Alexandria University Hospital, Egypt. Large hernia had an abdominal wall defect that could not be closed. Patients were divided into two groups of 30 patients according to the type of mesh used to deal with the large abdominal wall defect., Results: The study included 38 women (63.3 %) and 22 men (37.7 %); their mean age was 46.5 years (range, 25-70). Complicated incisional hernia was the commonest presentation (56.7 %).The operative and mesh fixation times were longer in the polypropylene group. Seven wound infections and two recurrences were encountered in the propylene group. Mean follow-up was 28.7 months (2-48 months)., Conclusions: Composite mesh provided, in one session, satisfactory results in patients with complicated large ventral hernia. The procedure is safe and effective in lowering operative time with a trend of low wound complication and recurrence rates.

Objective: To evaluate the impact of prolapse meshes on vaginal smooth muscle structure (VaSM) and function, and to evaluate these outcomes in the context of the mechanical and textile properties of the mesh., Design: Three months following the implantation of three polypropylene prolapse meshes with distinct textile and mechanical properties, mesh tissue explants were evaluated for smooth muscle contraction, innervation, receptor function, and innervation density., Setting: Magee-Womens Research Institute at the University of Pittsburgh., Population: Thirty-four parous rhesus macaques of similar age, parity, and pelvic organ prolapse quantification (POP-Q) scores., Methods: Macaques were implanted with mesh via sacrocolpopexy. The impact of Gynemesh(™)  PS (Ethicon; n = 7), Restorelle(®) (Coloplast; n = 7), UltraPro(™) parallel and UltraPro(™) perpendicular (Ethicon; n = 6 and 7, respectively) were compared with sham-operated controls (n = 7). Outcomes were analysed by Kruskal-Wallis ANOVA, Mann-Whitney U-tests and multiple regression analysis (P < 0.05)., Mean Outcome Measures: Vaginal tissue explants were evaluated for the maximum contractile force generated following muscle, nerve, and receptor stimulation, and for peripheral nerve density., Results: Muscle myofibre, nerve, and receptor-mediated contractions were negatively affected by mesh only in the grafted region (P < 0.001, P = 0.002, and P = 0.008, respectively), whereas cholinergic and adrenergic nerve densities were affected in the grafted (P = 0.090 and P = 0.008, respectively) and non-grafted (P = 0.009 and P = 0.005, respectively) regions. The impact varied by mesh property, as mesh stiffness was a significant predictor of the negative affect on muscle function and nerve density (P < 0.001 and P = 0.013, respectively), whereas mesh and weight was a predictor of receptor function (P < 0.001)., Conclusions: Mesh has an overall negative impact on VaSM, and the effects are a function of mesh properties, most notably, mesh stiffness., Tweetable Abstract: Prolapse mesh affects vaginal smooth muscle., Competing Interests: of interests None declared. Completed disclosure of interests form available to view online as supporting information., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Microscopic plastic fragments (<5 mm) are a worldwide conservation issue, polluting both coastal and marine environments. Fibers are the most prominent plastic type reported in the guts of marine organisms, but their effects once ingested are unknown. This study investigated the fate of polypropylene rope microfibers (1-5 mm in length) ingested by the crab Carcinus maenas and the consequences for the crab's energy budget. In chronic 4 week feeding studies, crabs that ingested food containing microfibers (0.3-1.0% plastic by weight) showed reduced food consumption (from 0.33 to 0.03 g d(-1)) and a significant reduction in energy available for growth (scope for growth) from 0.59 to -0.31 kJ crab d(-1) in crabs fed with 1% plastic. The polypropylene microfibers were physically altered by their passage through the foregut and were excreted with a smaller overall size and length and amalgamated into distinctive balls. These results support of the emerging paradigm that a key biological impact of microplastic ingestion is a reduction in energy budgets for the affected marine biota. We also provide novel evidence of the biotransformations that can affect the plastics themselves following ingestion and excretion.

The possibility of using gene therapy for the treatment of brain diseases such as brain cancer, Alzheimer's and Parkinson's diseases, is currently hampered by the lack of gene delivery systems able to cross the blood-brain barrier and deliver DNA to the brain following intravenous administration. On the basis that lactoferrin can effectively reach the brain by using specific receptors for crossing the blood-brain barrier, we propose to investigate if a lactoferrin-bearing generation 3-diaminobutyric polypropylenimine (DAB) dendrimer would allow the transport of plasmid DNA to the brain after intravenous administration. In this work, we demonstrated that the conjugation of lactoferrin to the dendrimer led to an enhanced DNA uptake by 2.1-fold in bEnd.3 murine brain capillary endothelial cells compared to the unmodified dendriplex in vitro. In vivo, the intravenous administration of lactoferrin-bearing DAB dendriplex resulted in a significantly increased gene expression in the brain, by more than 6.4-fold compared to that of DAB dendriplex, while decreasing gene expression in the lung and the kidneys. Gene expression in the brain was significantly higher than in any other major organs of the body. Lactoferrin-bearing generation 3 polypropylenimine dendrimer is therefore a highly promising delivery system for systemic gene delivery to the brain., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This study investigated the use of injectable poly(propylene fumarate) (PPF) formulations for mandibular fracture stabilization applications. A full factorial design with main effects analysis was employed to evaluate the effects of the PPF:N-vinyl pyrrolidone (NVP, crosslinking agent) ratio and dimethyl toluidine (DMT, accelerator) concentration on key physicochemical properties including setting time, maximum temperature, mechanical properties, sol fraction, and swelling ratio. Additionally, the effects of formulation crosslinking time on the mechanical and swelling properties were investigated. The results showed that increasing the PPF:NVP ratio from 3:1 to 4:1 or decreasing the DMT concentration from 0.05 to 0.01 v/w % significantly decreased all mechanical properties as well as significantly increased the sol fraction and swelling ratio. Also, increasing the crosslinking time at 37°C from 1 to 7 days significantly increased all mechanical properties and decreased both the sol fraction and swelling ratio. This study further showed that the flexural stiffness of ex vivo stabilized rabbit mandibles increased from 1.7 ± 0.3 N/mm with a traditional mini-plate fixator to 14.5 ± 4.1 N/mm for the 4:1 (0.05 v/w % DMT) PPF formulation at day 1. Overall, the formulations tested in this study were found to have properties suitable for potential further consideration in mandibular fracture fixation applications., (© 2014 Wiley Periodicals, Inc.)

Gemcitabine is currently the standard therapy for pancreatic cancer. However, growing concerns over gemcitabine resistance mean that new combinatory therapies are required to prevent loss of efficacy with prolonged treatment. Here, we suggest that this could be achieved through co-administration of RNA interference agents targeting the ubiquitin ligase ITCH. Stable anti-ITCH siRNA and shRNA dendriplexes with a desirable safety profile were prepared using generation 3 poly(propylenimine) dendrimers (DAB-Am16). The complexes were efficiently taken up by human pancreatic cancer cells and produced a 40-60% decrease in ITCH RNA and protein expression in vitro (si/shRNA) and in a xenograft model of pancreatic cancer (shRNA). When co-administered with gemcitabine (100 mg/kg/week) at a subtherapeutic dose, treatment with ITCH-shRNA (3x 50 mg/week) was able to fully suppress tumour growth for 17 days, suggesting that downregulation of ITCH mediated by DAB-Am16/shRNA sensitizes pancreatic cancer to gemcitabine in an efficient and specific manner., From the Clinical Editor: Gemcitabine delivery to pancreatic cancer often results in the common problem of drug resistance. This team overcame the problem through co-administration of siRNA and shRNA dendriplexes targeting the ubiquitin ligase ITCH., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of the present investigation was to assess and compare the effect of surface capping by different groups (-OH, -COOH and -NH2) on tumor targeting potential of folate conjugated poly (propylene imine) (PPI) (F-PPI) dendrimers using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay., Materials and Methods: The synthesized nanoconjugates (F-PPI, F-COOH-PPI, F-OH-PPI and F-CONH-PPI) were characterized by Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance ((1)H-NMR) and transmission electron microscopic (TEM) studies. The formulations were evaluated for drug entrapment, in vitro drug release and hemolytic toxicity, and cytotoxicity was evaluated on HeLa and SiHa cell line using MTT assay., Results: In case of all surface capped formulation, Methotrexate (MTX) loading was found to increased; however MTX release rate was found to decrease as compared to unmodified formulation. Further, F-COOH-PPI displayed highest tumor targeting potential as compared to other formulations. This is the first study to explore the effect of surface capping on the targeting potential of folate-conjugated fifth generation (5.0 G) PPI dendrimer., Conclusions: In conclusion, the targeting potential of all the formulations (anticancer activity) for both HeLa and SiHa cells follows in the following order: F-COOH-PPI > F-OH-PPI > F-CONH-PPI > F-PPI.

Introduction. Urinary diversion is very often associated with urinary retention and urinary incontinence. In this study, a surgical modification during cystectomy with orthotopic ileal neobladder is presented. Material and Methods. Female patients enrolled in the study (n-24) were subjected to sacrocolpopexy during the operation. Apart from oncological control, the follow-up consisted of 1-hour inlay test and questionnaires (UDI-6 and IIQ-7) in the 3rd, 6th, and 12th month after the operation. In the 12th month after the surgery, the urodynamic pressure-flow test was performed. Outcomes were compared with the control group (n-18) in which sacrocolpopexy was not implemented. Results. The study group was characterised by reduced urinary retention and improved continence. Conclusion. Sacrocolpopexy during cystectomy with orthotopic ileal bladder is a valuable surgical method which provides patients with a better quality of life.

Poly(propylene imine) (PPI) glycodendrimers are promising candidates as drug carriers and antiamyloidogenic and antiprionic agents. In this study the anti-β-amyloid capacity of PPI glycodendrimers of the fourth and fifth generations was investigated in vitro and in vivo. We assessed distinct PPI glycodendrimers including G4mDS and G5mDS, with electroneutral maltose shell, and G4mOS and G4m-IIIOS, with cationic maltose or maltotriose shell. Our results show that in vitro PPI maltose dendrimers reduce the toxicity of Aβ(1-42). However, only the electroneutral maltose dendrimers G4mDS and G5mDS reduce the toxicity of Alzheimer's disease brain extracts in SH-SY5Y neuroblastoma cells. PPI maltose dendrimers with electroneutral or cationic surface penetrate the cytoplasm of cultured cells, and they reach the brain when administered intranasally. Both cationic G4mOS and electroneutral G4mDS are able to modify the total burden of β-amyloid in APP/PS1 mice. The studied dendrimers did not reverse memory impairment in APP/PS1 mice following chronic administration; moreover, cationic G4mOS caused cognitive decline in nontransgenic mice. In spite of the capacity of G4mDS and G4mOS to cross the blood-brain barrier and modulate Aβ aggregation in APP/PS1 mice, further studies are needed to learn how to reduce the harmful effects of maltose dendrimers in vivo.

Objectives: Volatile anesthetics have cardioprotective properties that improve clinically relevant outcomes in cardiac surgery, and can be used during cardiopulmonary bypass (CPB) through adapted calibrated vaporizers together with air and oxygen (O2). The effect of volatile agents on the membrane oxygenator is unknown. The aim of this study was to evaluate, for the first time, the performance of semiporous polypropylene membrane oxygenators after the use of sevoflurane vaporized during CPB in cardiac surgery., Design: A prospective, randomized, controlled trial., Setting: Teaching hospital., Participants: Thirty-two consecutive patients scheduled to undergo coronary artery bypass graft with CPB., Interventions: Patients were allocated randomly to receive either a volatile anesthetic (sevoflurane 1%-3%, 16 patients) or an intravenous hypnotic (midazolam, 16 patients) during CPB. After surgery, the membrane oxygenators used during CPB were tested with regard to O2 transfer, carbon dioxide transfer, and pressure drop., Measurements and Main Results: The authors observed no protocol deviation or crossover. The performance of the membrane oxygenator was similar between the 2 groups, as documented by O2 transfer (55±6.4 mL/min/L in the sevoflurane group versus 57±4.7 mL/min/L in the midazolam group, p = 0.4), carbon dioxide transfer, and pressure drop., Conclusions: The use of sevoflurane during CPB in cardiac surgery does not affect membrane oxygenator performance., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The purpose of the current investigation was to explore the potential of polypropylene imine (PPI) dendrimers to deliver dithranol (DIT) topically and to evaluate its encapsulation, permeation and skin irritation potential. PPI (5.0 generation, 5.0 G) dendrimers and DIT-loaded PPI (DIT-PPI) were prepared and characterized by spectroscopy and transmission electron microscopy. DIT encapsulation, in vitro skin permeation study, skin irritation studies, fluorescent studies and tape stripping studies were performed. Loading of DIT was found to be pH dependent with maximum encapsulation at acidic pH (1.0 ± 0.02, 17.2 ± 0.56 and 57.1 ± 1.32% at 7.4, 5.5 and 1.2 pH, respectively). DIT-PPI showed significantly enhanced permeation rate constant and lesser skin irritation (11.61 ± 1.80 μg/cm(2)/h and 1.0, respectively) when compared with the plain DIT solution (2.72 ± 0.31 μg/cm(2)/h and 2.3, respectively). Skin separation studies and confocal laser scanning microscope images showed that the dye-loaded dendrimers exhibits deposition of dye in pilosebaceous compartment. These studies demonstrate that PPI can be exploited to improve the topical bioavailability of the molecules in a controlled pattern. The enhanced accumulation of DIT via dendrimer carrier within the skin might help optimize targeting of this drug to the epidermal and dermal sites, thus creating new opportunities for well-controlled, modern topical application of DIT for the treatment of psoriasis.

The aim of this study was to clarify the relationship between the concentration of Pluronic P123/F127 block copolymers and P-glycoprotein (P-gp) inhibitory potency. Modulation of multidrug resistance (MDR) by Pluronic P123/F127 was evaluated in P-gp over-expressing human breast cancer cell line MCF-7/ADR and its non-P-gp over-expressing counterpart MCF-7 cells. Four different probes (known as P-gp substrates) including rhodamine 123 (R-123), rhodamine 6G (R-6G), doxorubicin (DOX), and paclitaxel (PTX) were applied to investigate the impact of Pluronic P123/F127 copolymers with different concentrations on the intracellular accumulation of these probes. Additionally, the intracellular ATP and mitochondrial transmembrane potential in MCF-7/ADR cells were determined over a wide concentration range of Pluronic P123/F127. Furthermore, the endocytic mechanisms of Pluronic micelles were performed. It was suggested that P-gp substrate hydrophobicity and the concentration of P123/F127 copolymers had little impact on P-gp inhibitory activity of Pluronic P123/F127 itself. Intracellular ATP depletion was the main mechanism of Pluronic P123/F127 for P-gp inhibition. In vitro cytotoxicity study was also conducted in order to compare cytotoxic effect among different PTX formulations. It indicated that the IC50 of PTX-loaded Pluronic P123/F127 mixed micelles was 6.3-fold lower than free PTX and 2.3-fold lower than Taxol, respectively. Therefore, Pluronic P123/F127 polymeric micelles could be considered a promising drug delivery system to overcome MDR in cancer therapy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Calcium phosphate-based transfection method had been used to transfer DNA into living cells. However, it had so far not been studied in detail to what extend siRNA delivery system. In this study, Pluronic F127/calcium phosphate hybrid nanoparticles (F127/CaP) were prepared by a facile room temperature method and employed as carriers to deliver siRNA to silence tumor cell. The morphology of the F127/CaP hybrid nanoparticles was investigated with TEM. In order to determine the ratio of F127 to CaP in the hybrid nanoparticles, TGA (the thermogravimetric analysis) was applied. MTT assays confirmed that the F127/CaP hybrid nanoparticles were quite safe. The hybrid F127/CaP nanoparticles obtained were 120-210 nm in diameter, and they were applied as siRNA carriers for siRNA loading and in vitro transfection. The siRNA encapsulating efficiency was 91.5 wt.% with a loading content of 6.5 wt.%. Compared to traditional CaP transfection method, the siRNA-loaded F127/CaP exhibited higher gene inhibition efficiency, and this was supported by fluorescence microscopy. Quantitative analysis of GFP silencing efficiency of various siRNA formulations was measured by using FACS flow cytometry analysis. Additionally, both custom CaP and F127/CaP are biocompatible and biodegradable, thus the as-prepared F127/CaP hybrid nanoparticles are promising for siRNA delivery.

The competitive interactions between the poly-[propylene oxide] (POO)-poly-[ethylene oxide] (PEO) block copolymer poloxamer 407 (Pluronic F127) and two drugs, triamcinolone acetonide and ciclopirox olamine, by the formation of inclusion complexes with two cyclodextrin hydrophilic derivatives, hydroxypropyl-β-cyclodextrin (HPβCD; molar substitution (MS) 0.65) and partially methylated-β-cyclodextrin (MβCD; MS 0.57), were studied by means of one-dimensional (1)H NMR, 2D ROESY experiments, solubility studies and drug release studies. 1D and 2D NMR and solubility studies indicate that both triamcinolone acetonide and ciclopirox olamine form stable inclusion complexes with the cyclodextrin derivatives. In the case of ciclopirox olamine the complex was more stable at pH 1. Effective complexation of poloxamer with the two cyclodextrins (CDs) was also evidenced by NMR analysis, and competitive displacement of the drugs from the CD cavity by the polymer was observed. Drug solubility in CD solutions was not modified by the addition of polymers, indicating that a decrease in solubility due to the competitive displacement is probably compensated by the solubilizing effect of polymer micellization. Finally, polypseudorotaxanes formation has a significant influence on the release of the drugs studied. Changes in the release rate depend on the stability of drug-CD inclusion complex and on cyclodextrin concentration in the bulk solution; so polypseudorotaxane formation can be employed to modulate drug controlled release from thermosensitive hydrogels., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To optimize the matrix formulation of compound Die Da Zhen Tong cataplasm., Methods: The optimal preparation was selected by U17 (17(16)) uniform design, independent variables were the percentage ratio of the matrix formulation component part in compound Die Da Zhen Tong cataplasm,and the viscosity, continued viscosity and overall desirability used as indexes were dependent variables., Results: The percentage of the matrix formulation component part in compound Die Da Zhen Tong cataplasm was, NP-700: carbomer 980: PVP K-90: dihydroxy aluminum: tartaric: kaolinite: sorbitol: glycerin = 5: 1. 2: 2.5: 0.25: 0.15:4: 12: 5., Conclusion: The optimized cataplasm has good viscosity, continued viscosity and high overall desirability.

Degradable polymer nanoparticles (NPs, 50 nm) based on polypropylene sulfide (PPS) were conjugated to thiolated antigen and adjuvant proteins by reversible disulfide bonds and evaluated in mucosal vaccination. Ovalbumin was used as a model antigen, and antigen-conjugated NPs were administered intranasally in the mouse. We show penetration of nasal mucosae, transit via M cells, and uptake by antigen-presenting cells in the nasal-associated lymphoid tissue. Ovalbumin-conjugated NPs induced cytotoxic T lymphocytic responses in lung and spleen tissues, as well as humoral response in mucosal airways. Co-conjugation of the TLR5 ligand flagellin further enhanced humoral responses in the airways as well as in the distant vaginal and rectal mucosal compartments and induced cellular immune responses with a Th1 bias, in contrast with free flagellin. The PPS NP platform thus appears interesting as a platform for intranasally-administered mucosal vaccination for inducing broad mucosal immunity., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Carboxy terminated-poly(propylene fumarate)-co-ethylene glycol) (CT-PPF-co-PEG) was prepared and set into crosslinked hydrogel material with acrylamide. The setting studies reveal that this copolymer system can be used as an injectable material. The hydrogel material exhibits a higher degree of swelling, good mechanical strength and flexibility. The hydrogel favours adhesion of L929 fibroblast cells without proliferation on the surface. However, cardiac fibroblast cells (isolated from new born rat (Wistar) hearts) adhere and proliferate on the hydrogel due to the formation of synergistic hydrophilic-hydrophobic surface-by-surface reorganization.

This study has analyzed fracture morphology of four nonabsorbable commercially available sutures before and after implantation in rats. Also, tensile and knot strength retention have been evaluated after 3 and 8 weeks in vivo. Scanning electron and optical light microscopes were used for analysis of fracture morphologies and surface changes of the sutures. A clear effect of in vivo on the tensile and knot strength changes, and the fracture mechanism was seen for braided sutures. The suture size was also important for braided sutures, as fibrous tissue formation plays an important role in terms of the size. The fiber's surface properties were also important for the fracture morphology. A smooth and even surface was not suitable for the fibrous tissue formation as seen in monofilament sutures. Therefore, the polymer type was very important for the monofilament sutures, as it was the most important parameter to determine the fracture morphology and was not affected by the implantation and the implantation time. The size of the suture was also important for the polypropylene in terms of axial splitting before and after implantation. This, however, was not the case for knot strength tests. The knot was undone regardless of the size. Surface characteristics were very important for braided sutures, as they have a rough surface that supports tissue formation on the fracture mechanism, tensile and knot strength. Silk suture has single filaments with no regular diameter and smooth surface. Therefore, silk suture has more tissue formation postimplantation compared to polyester suture.

Vertebral compression fractures cause pain, deformity, and disability. Polypropylene fumarate (PPF) has shown promise as an injectable cement for bone defects but little is known about its performance for kyphoplasty. The purpose of this study was to evaluate the biomechanical performance of PPF for kyphoplasty in simulated anterior compression fractures in cadaveric vertebral bodies. Thirty-one vertebral bodies (T9 to L4) from osteoporotic cadaveric spines were disarticulated, stripped of soft tissue and compressed on a materials testing machine to determine pretreatment strength and stiffness. All fractures were repaired with inflatable balloon tamps and either polymethylmethacrylate or PPF-30 (containing 30% barium sulfate by dry weight) cement and then retested. Strength restoration with PMMA and PPF-30 were 120% and 104%, respectively, of the pretreatment strengths. For stiffness, PMMA and PPF-30 restored vertebral bodies to 69% and 53%, respectively, of the initial values. There was no significant difference in treatment with either PMMA or PPF-30. The biopolymer PPF-30 exhibits mechanical properties similar to PMMA in a cadaveric kyphoplasty model. PPF biopolymer may be a suitable alternative for kyphoplasty.

Fifty-nine dogs with a total of 69 perineal hernias that were repaired by internal obturator transposition and polypropylene mesh reinforcement were reviewed. Thirty-six dogs were available for follow-up at a mean of 29.4 months postoperatively. Six dogs had complications within the first 60 days of surgery, such as perineal swelling, persistent tenesmus, and incisional infections. Twenty-two dogs had excellent outcomes; seven dogs needed continued medical treatment after surgery; and seven dogs had poor outcomes. Hernias recurred in five dogs. The incisional infection rate was 5.6%; the recurrence rate was 12.5%; and the overall success rate was 80.5% for the 36 dogs with long-term follow-up.

Conclusion: Since this tissue engineering technique is cost-effective and is less invasive to patients, it may replace conventional approaches in laryngeal reconstructive surgeries., Objective: Laryngeal cancer is one of the most prevalent cancers in the head and neck region, and frequently requires surgical resection. Although there are many ways to reconstruct the larynx after resection, donor tissue is usually required. Recently, tissue engineering techniques have become widely accepted in clinical medicine and have already been applied to some organs. This animal experiment was designed to elucidate the efficacy of laryngeal regeneration using tissue engineering technique., Materials and Methods: A bioartificial scaffold was designed from a replica of a canine larynx. A dental cast was used to replicate the intricate inside shape of the larynx. After copying its shape on a polypropylene mesh sheet, this sheet was coated with spongy collagen from porcine skin. A hemilaryngectomy was performed on beagle dogs under general anesthesia. Then the scaffold, preclotted with a mixture of peripheral blood and bone marrow-derived stromal cells, was implanted and fixed. The postoperative status was examined fiberscopically., Results: On the eighth day after the operation, the surface of the implant was covered with soft tissue. Finally, the implant was completely covered with regenerated mucosa.

In the present study it was intended to deliver primaquine phosphate (PP), a liver schizonticide directly to liver cells using polypropyleneimine (PPI) dendrimers-coated peripherally with galactose. PPI dendrimers were synthesized by consecutive Michael double addition reaction (using ethyelenediamine as core), followed by hydrogenation reaction. Galactose conjugation was carried out by ring opening reactions, followed by Schiff's reaction and reduction to secondary amine in sodium acetate buffer (pH 4.0). IR, NMR, MASS spectroscopy were used for the confirmation of synthesis of uncoated and coated dendrimers. The formulations were made by equilibrium dialysis of dendrimers with the solution of PP. Then the formulations were characterized by TEM for size and shape. Release rate, hemolytic toxicity; bio-distribution and blood level studies were also performed on lyophilized formulations. The results obtained indicated that galactose coating of PPI systems increases the drug entrapment efficiency by 5-15 times depending upon generations. Galactose coating prolonged release up to 5-6 days as compared to 1-2 days for uncoated PPI systems. The hemolytic toxicity, blood level and hematological studies proved these systems to be safer and suitable for sustained drug delivery. Blood level studies proved the suitability of the systems for the prolonged circulations and delivery of PP to liver. The galactose coating of PPI dendrimers can therefore make the PPI systems more effective and suitable for targeted delivery of Primaquine phosphate to liver.

Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration.

Background: Complications such as heart failure due to insufficient cardioplegia may develop in on-pump coronary artery bypass (CAB) with mild-to-moderate aortic regurgitation (AR). A technique for administration of cardioplegic solution was carried out to avoid such complications., Methods and Results: Cardiopulmonary bypass was established. After aortic cross-clamping, cardioplegic solution was administered from aortic root. Because complete cardiac arrest was not rapidly achieved, the aortic root was incised. Three cusps of the aortic valve were sutured. The aorta was closed; cardioplegic solution was administered from the aortic root. Then, cardiac arrest was rapidly achieved. After distal anastomosis of quadruple bypass was completed, the suture of the cusps was removed. There was no exacerbation of AR due to this method compared to the preoperative state., Conclusion: When off-pump coronary artery bypass is impossible and retrograde cardioplegia cannot be performed for a certain reason, this method may be set to one of the choices.

Background: Temporary abdominal wound closure is sometimes desirable when tension-free approximation of the wound edges is impractical or when reexploration is planned., Methods: The behavior of a composite prosthesis (PL-PU99) designed by our group was evaluated as a method of temporary abdominal closure in white New Zealand rabbits. After a 7 cm long midline laparotomy, a spindle-shaped 4 cm (maximum width) by 7 cm (length) fragment of PL-PU99 was sutured to the edges of the peritoneal, muscular, and fascial abdominal tissues, so that the biomaterial remained in contact with the exterior. The PL-PU99 composite is composed of a polypropylene mesh adhered to a sheet of polyurethane with an acrylic cement. At 7 and 14 days after implant, animals were sacrificed and specimens taken for morphological, ultrastructural, morphometry of the neoperitoneum, and immunohistochemical (macrophage reaction, RAM-11) analysis., Results: No death or signs of infection or rejection of the prostheses were recorded. No adhesions could be macroscopically observed between the composite and the intestinal loops. The biomaterial achieved a good seal, no leakage of fluids being detected. Fourteen days after implant, the neoperitoneum formed on the prosthesis was of an even structure and was made up of organized, vascularized connective tissue covered by an uninterrupted mesothelium., Conclusions: The PL-PU99 prosthesis shows optimal behavior at the prosthesis/visceral peritoneum interface, making it ideal for its use in the temporary closure of the abdomen. The implanted composite may also prove useful for the permanent repair of the abdominal wall., (Copyright 2004 Excerpta Medica, Inc.)

We used polypropylenimine dendrimers for delivering a 31 nt triplex-forming oligonucleotide (ODN) in breast, prostate and ovarian cancer cell lines, using 32P-labeled ODN. Dendrimers enhanced the uptake of ODN by approximately 14-fold in MDA-MB-231 breast cancer cells, compared with control ODN uptake. Dendrimers exerted their effect in a concentration- and molecular weight-dependent manner, with generation 4 (G-4) dendrimer having maximum efficacy. A similar increase in ODN uptake was found with MCF-7 and SK-BR-3 (breast), LNCaP (prostate) and SK-OV-3 (ovarian) cancer cells. The dendrimers had no significant effect on cell viability at concentrations at which maximum ODN uptake occurred. [3H]Thymidine incorporation showed that complexing the ODN with G-4 significantly increased the growth-inhibitory effect of the ODN. Western blot analysis showed a significant 65% reduction of c-myc protein level in ODN-G-4 treated cells compared with that of ODN-treated/control cells. Gel electrophoretic analysis showed that ODN remained intact in cells even after 48 h of treatment. The hydrodynamic radii of nanoparticles formed from ODN in the presence of the dendrimers were in the range of 130-280 nm, as determined by dynamic laser light scattering. Taken together, our results indicate that polypropylenimine dendrimers might be useful vehicles for delivering therapeutic oligonucleotides in cancer cells.