NF-κB Decoy Oligodeoxynucleotide-Loaded Poly Lactic-co-glycolic Acid Nanospheres Facilitate Socket Healing in Orthodontic Tooth Movement.

Orthodontic space closure following tooth extraction is often hindered by alveolar bone deficiency. This study investigates the therapeutic use of nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides loaded with polylactic-co-glycolic acid nanospheres (PLGA-NfDs) to mitigate alveolar bone loss during orthodontic tooth movement (OTM) following the bilateral extraction of maxillary first molars in a controlled experiment involving forty rats of OTM model with ethics approved. The decreased tendency of the OTM distance and inclination angle with increased bone volume and improved trabecular bone structure indicated minimized alveolar bone destruction. Reverse transcription-quantitative polymerase chain reaction and histomorphometric analysis demonstrated the suppression of inflammation and bone resorption by downregulating the expression of tartrate-resistant acid phosphatase, tumor necrosis factor-α, interleukin-1ß, cathepsin K, NF-κB p65, and receptor activator of NF-κB ligand while provoking periodontal regeneration by upregulating the expression of alkaline phosphatase, transforming growth factor-ß1, osteopontin, and fibroblast growth factor-2. Importantly, relative gene expression over the maxillary second molar compression side in proximity to the alveolus highlighted the pharmacological effect of intra-socket PLGA-NfD administration, as evidenced by elevated osteocalcin expression, indicative of enhanced osteocytogenesis. These findings emphasize that locally administered PLGA-NfD serves as an effective inflammatory suppressor and yields periodontal regenerative responses following tooth extraction.

NF-κB Decoy ODN-Loaded Poly(Lactic-co-glycolic Acid) Nanospheres Inhibit Alveolar Ridge Resorption.

Residual ridge resorption combined with dimensional loss resulting from tooth extraction has a prolonged correlation with early excessive inflammation. Nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides (ODNs) are double-stranded DNA sequences capable of downregulating the expression of downstream genes of the NF-κB pathway, which is recognized for regulating prototypical proinflammatory signals, physiological bone metabolism, pathologic bone destruction, and bone regeneration. The aim of this study was to investigate the therapeutic effect of NF-κB decoy ODNs on the extraction sockets of Wistar/ST rats when delivered by poly(lactic-co-glycolic acid) (PLGA) nanospheres. Microcomputed tomography and trabecular bone analysis following treatment with NF-κB decoy ODN-loaded PLGA nanospheres (PLGA-NfDs) demonstrated inhibition of vertical alveolar bone loss with increased bone volume, smoother trabecular bone surface, thicker trabecular bone, larger trabecular number and separation, and fewer bone porosities. Histomorphometric and reverse transcription-quantitative polymerase chain reaction analysis revealed reduced tartrate-resistant acid phosphatase-expressing osteoclasts, interleukin-1ß, tumor necrosis factor-α, receptor activator of NF-κB ligand, turnover rate, and increased transforming growth factor-ß1 immunopositive reactions and relative gene expression. These data demonstrate that local NF-κB decoy ODN transfection via PLGA-NfD can be used to effectively suppress inflammation in a tooth-extraction socket during the healing process, with the potential to accelerate new bone formation.

Regeneration of Functional Bladder Using Cell-seeded Amnion and P(LA/CL) Scaffolds.

Long-term bladder regeneration has not been successful instead of augmentation with gastrointestinal segments, as is commonly performed for bladder reconstruction. To evaluate whether or not cell-seeded bioabsorbable materials regenerate half-resected bladder in a rabbit model. Female Japanese white rabbits were divided two groups: cell-seeded material (CSM) group and Control (n = 6 each). Control rabbits underwent resection of half the bladder. CSM rabbits were sutured with cell-seeded amniotic membrane and P(LA/CL) material after bladder resection. After 6, 12, and 18 months, rabbits underwent X-ray and cystometry, and bladder tissues after 18 months were subjected to functional and histological analyses. X-ray confirmed the peristaltic movements of the reconstructed bladders in the CSM group. On cystometry, the mean maximum bladder volume, maximum bladder pressure, and 25 mL bladder volume compliance in the CSM group were significantly greater than in the Control group at 6, 12, and 18 months. In addition, organ bath studies showed good contraction under electrical stimulation with increasing stimulation frequency in the CSM group, while, the Control group showed weak contraction on both tests in the central marginal zone. Furthermore, the rates of neovascularization, urothelial and smooth muscle formation, and neurofilamentation in the CSM group were significantly greater than in the Control group. Oral mucosal cell-seeded amniotic membrane and stomach smooth muscle cell-seeded P(LA/CL) scaffold with omentum after abdominal implantation regenerated functional bladder with satisfactory epithelium and smooth muscle without scarring more than 1 year. Impact Statement Regeneration of functional bladder without using gastrointestinal segments has been a huge challenge to urological reconstruction. Various materials, such as nonbioabsorbable materials and biomaterials have been attempted to reconstruct bladder in animal models. However, the long-term results more than a year failed due to the low biocompatibility, high risks, and difficulty creating the materials. In this study, we revealed long-term bladder regeneration using cell-seeded amniotic membrane and P(LA/CL) material in a rabbit model. The new method of bladder reconstruction seems able to regenerate functional bladder with satisfactory bladder epithelium and bladder smooth muscle function without scarring for more than 1 year successfully.

Risk factors for postoperative bleeding and early death in percutaneous endoscopic gastrostomy: A multicenter retrospective study.

BACKGROUND AND AIM: Comprehensive reports on the risk factors for bleeding and early death after percutaneous endoscopic gastrostomy (PEG) are limited. In this multicenter study, we retrospectively investigated the risk factors for bleeding and early death after PEG. METHODS: Patients (n = 1234) who underwent PEG between 2015 and 2020 at Osaka Medical and Pharmaceutical University and its affiliated hospitals (11 institutions in total) were evaluated for postoperative bleeding and early death (within 60 days) after PEG according to patient characteristics, construction method, medical history, medications, preoperative hematological findings, and perioperative adverse events. Multivariate logistic regression was performed to identify independent predictors of bleeding and early death after PEG. RESULTS: The risk factors for bleeding after PEG were PEG tube insertion using the modified introducer method (odds ratio [OR], 4.37; P = 0.0003), low platelet count (OR, 0.99; P = 0.014), antiplatelet therapy (OR, 2.11; P = 0.036), and heparinization (OR, 4.50; P = 0.007). Risk factors for early death were low body mass index (BMI) (OR, 0.89; P = 0.015), low serum albumin levels (OR, 0.50; P = 0.035), and comorbidity of active cancer (OR, 4.03; P < 0.0001). There was no significant association between bleeding and early death after PEG. CONCLUSIONS: We identified several risk factors for bleeding and early death after PEG. Risk factors for bleeding were PEG tube insertion using the modified introducer method, low platelet count, antiplatelet therapy, and heparinization. Risk factors for early death were low BMI, low serum albumin levels, and comorbidity of active cancer.

Effect of a proton-pump inhibitor on intestinal microbiota in patients taking low-dose aspirin.

BACKGROUND AND AIM: Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users. METHODS: Thirty-two recruited patients, who received LDA (100 mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20 mg/day) and 17 patients additionally receiving vonoprazan (10 mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured. RESULTS: Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p < 0.0001) than in the esomeprazole group (p = 0.0024). The Lactobacillales proportion was positively correlated with the gastrin level (r = 0.5354). No significant hemoglobin or hematocrit level reduction was observed in subjects receiving LDA with additional PPI. CONCLUSIONS: Additional PPI administration increased the Lactobacillales proportion in the microbiota of LDA users. The positive correlation between the gastrin level and the proportion of Lactobacillales suggested that the change in the intestinal flora was associated with the degree of suppression of gastric acid secretion. Additional oral PPI did not significantly promote anemia, but the risk of causing PPI-induced small-intestinal mucosal injury in LDA users should be considered.

Effects of Fiber Diameter and Spacing Size of an Artificial Scaffold on the In Vivo Cellular Response and Tissue Remodeling.

By mimicking the extracellular matrix, nonwoven fabrics can function as scaffolds for tissue engineering application ideally, and they have been characterized regarding their fiber diameter and fiber spacing (spacing size) in vitro. We chronologically examined the in vivo effects of these fabrics on the cellular response and tissue remodeling. Four types of nonwoven polyglycolic acid fabrics (Fabric-0.7, Fabric-0.9, Fabric-3, and Fabric-16 with fiber diameters of 0.7, 0.9, 3.0, and 16.2 µm and spacing sizes of 2.0, 19.3, 19.0, and 825.4 µm, respectively) were implanted into the rat dorsum and subjected to histologic and immunohistochemical analyses from day 3 to 70. With Fabric-0.7, inflammatory cells (mainly M1 macrophages) and myofibroblasts with collagen type III accumulated mainly on the surface of the fabric and did not infiltrate inside the fabric initially, likely due to the narrow fiber space. Massive formation of collagen type I then appeared with the degradation of the fabrics, and finally, the remodeled tissue turned into a dense scar. With Fabric-0.9 and Fabric-3, inflammatory cells (predominantly M2 macrophages) were seen in all layers of the fabric initially. A mild increase in collagen type I was then seen, with few myofibroblasts, and the remodeled tissue ultimately showed a relatively little scar with an adequate thickness of the tissue induced by the fabrics. With Fabric-16, inflammatory cells (predominantly M1 macrophages) infiltrated into all layers of the fabric initially along with many myofibroblasts, especially in the hole. Lately, massive formation of collagen type I was noted due to the slow degradation of the fabric, with the shrinking of the fabric substantially, and the remodeled tissue finally turned to a dense scar. These findings suggest that optimizing the spacing size as well as the fiber diameter of artificial scaffolds may control the cellular response and tissue remodeling and facilitate favorable tissue regeneration without scar formation.

The usefulness of re-attachability of anti-adhesive cross-linked gelatin film and the required physical and biological properties.

BACKGROUND: To overcome the unfavorable issues associated with conventional anti-adhesive HA/CMC film, we developed an anti-adhesive thermally cross-linked gelatin film. OBJECTIVE: We tried to clarify the re-attachability of the film and the required properties concerning the film thickness, stiffness and anti-adhesion effect. METHODS: To determine the optimal thickness, 5 kinds of the thickness of gelatin film and the conventional film were analyzed by the tensile test, shearing test, buckling test and tissue injury test. Finally, using the optimal film thickness, we tried to clarify the anti-adhesion effect of the reattached film. RESULTS: The tensile and shearing test showed gelatin films ≥30 µm thick had greater tensile strength and a smaller number of film fractures, than the conventional film. The buckling and tissue injury test showed gelatin films ≥60 µm thick had higher buckling strength and worse injury scores than the conventional film. The anti-adhesive effect of re-attached gelatin film using optimal thickness (30-40 µm) found the anti-adhesion score was significantly better than that of the control. CONCLUSIONS: Provided it has an optimal thickness, gelatin film can be reattached with enough physical strength not to tear, safety stiffness not to induce tissue injury, and a sufficient anti-adhesion effect.

IFN-Alpha1 antisense RNA represses human influenza A virus growth in a guinea pig system.

We reported a natural antisense (AS) long non-coding RNA as an important modulator of interferon-Alpha1 (IFNA1) mRNA levels. We showed that IFN-Alpha1 AS promotes IFNA1 mRNA stability by transient duplex formation and inhibition of miR-1270-induced mRNA decay. Here, we performed a proof-of-concept experiment to verify that the AS-mRNA regulatory axis exerts in vivo control of innate immunity. We established a model system for influenza virus infection using guinea pig, which encodes a functional MX1 gene for the type I IFN pathway. This system allowed us to investigate the effects of antisense oligoribonucleotides representing functional domains of guinea pig IFN-Alpha1 AS on gpIFNA1 mRNA levels and, consequently, on viral proliferation in the respiratory tract of influenza virus-infected animals. We demonstrated that pulmonary-administered asORNs inhibited the proliferation of the virus in the animals by modulating IFNA1 mRNA levels. These results indicate that, in light of the proposed actions, asORNs may modulate the level of IFNA1 mRNA in vivo, indicating that IFN-Alpha1 AS plays a pivotal role in determining the outcome of type I IFN responses.

Periocular injection of candesartan-PLGA microparticles inhibits laser-induced experimental choroidal neovascularization.

PURPOSE: Microparticle technology enables local administration of medication. The purpose of this study was to examine the inhibitory effect of locally administered candesartan (CAN)-encapsulated microparticles on experimental choroidal neovascularization (CNV). METHODS: Laser photocoagulation was used to induce CNV in Brown Norway rats. The rats were pretreated with subconjunctival injections of CAN (5.0 mg/eye) or phosphate buffer saline for 3 days before photocoagulation. The volume of CNV was evaluated 7 days after laser injury using the lectin staining technique. The infiltration of macrophages within the CNV lesion was determined using immunofluorescent staining with an anti-CD68 antibody. mRNA levels of MCP-1, IL1-ß and VEGF in the retinal pigment epithelium/choroid complex were determined using quantitative PCR (q-PCR). RESULTS: CNV volume was significantly suppressed by the treatment with CAN compared with that in vehicle-treated eyes (P<0.05, two-tailed Student's t-test). Subconjunctival injections of CAN decreased the numbers of CD68+ cells in the CNV lesion. The increased mRNA levels of MCP-1, IL1-ß, and VEGF induced by photocoagulation was significantly suppressed following the local administration of CAN (P<0.05, two-tailed Student's t-test). CONCLUSION: Local administration of CAN inhibited experimentally induced CNV possibly through anti-inflammatory effects.

A Novel Bioabsorbable Sheet That Delivers NF-κB Decoy Oligonucleotide Restrains Abdominal Aortic Aneurysm Development in Rats.

For the suppression of inflammation in the aneurysm development, we focused on inhibition of an important transcription factor, nuclear factor-kappa B (NF-κB), using a decoy strategy. We newly developed a novel bioabsorbable sheet that delivers NF-κB decoy oligodeoxynucleotide (ODN).We treated 5-week-old SD rats that were induced with abdominal aortic aneurysm (AAA) using 0.5 M CaCl2 with an NF-κB decoy sheet. Four weeks after AAA induction, aortic tissue was excised for further examinations. We showed that this bioabsorbable sheet could deliver the decoy ODN into the target tissues and dissolve within a week. Treatment with the NF-κB decoy sheet reduced the aneurysm size compared with the controls. It also suppressed inflammation due to the effect of NF-κB decoy ODN. Immunohistochemistry revealed that the expression of CD31, CD4, and CD11b in the NF-κB decoy sheet group was significantly lower than in the control sheet group. The NF-κB decoy sheet was absorbed on the target tissue.We have revealed that the bioabsorbable sheet mediated decoy ODN is effective for transfection into target organs. We have also indicated that NF-κB decoy ODN transfection using this sheet has the potential to suppress the dilatation of aneurysm. The bioabsorbable sheet mediated transfection of the decoy ODN can be beneficial for the clinical treatment of AAA and other NF-κB-related cardiovascular diseases.

Newly Developed Polyglycolic Acid Reinforcement Unified with Sodium Alginate to Prevent Adhesion.

Polyglycolic acid (PGA) mesh fabric is widely used for reinforcing injured tissues during surgeries. However, PGA induces chronic inflammation and adhesion. The purpose of this study is to develop PGA reinforcement "without PGA-induced adhesion." We developed a reinforcement fabric unified with PGA mesh and alginate foam. The antiadhesive effects of sodium alginate foam and calcium alginate foam were evaluated in rats. Sodium alginate foam unified with PGA mesh fabric exhibited strong effects that limit the extent and severity of adhesion, whereas calcium alginate foam unified with PGA mesh was less effective in preventing adhesion. In the sodium alginate group, fibroblasts and collagen fibers around implanted sites were sparse and the material degraded rapidly by macrophage ingestion. Fibroblasts and collagen fibers play a major role in adhesion formation and their excessive proliferation results in postoperative adhesion. Thus, inhibiting their increase is the key in preventing PGA-induced adhesion. The reinforcement that is composed of PGA mesh unified with sodium alginate foam strongly inhibited PGA-induced adhesion and showed excellent handling during surgery and could be easily applied with a one-step procedure.

Reduction of Pulmonary Air Leaks with a Combination of Polyglycolic Acid Sheet and Alginate Gel in Rats.

Postoperative air leaks remain a major cause of morbidity after lung resection. This study evaluated the effect of a combination of polyglycolic acid (PGA) sheet and alginate gel on pulmonary air leaks in rats. Four pulmonary sealing materials were evaluated in lung injury: fibrin glue, combination of PGA sheet and fibrin glue, alginate gel, and combination of PGA sheet and alginate gel. With the airway pressure maintained at 20 cmH2O, a 2 mm deep puncture wound was created on the lung surface using a needle. Lowering the airway pressure to 5 cmH2O, each sealing material was applied. The lowest airway pressure that broke the seal was measured. The seal-breaking pressure in each experimental group was fibrin, 10.4 ± 6.8 cmH2O; PGA + fibrin, 13.5 ± 6.5 cmH2O; alginate gel, 10.3 ± 4.9 cmH2O; and PGA + alginate, 35.8 ± 11.9 cmH2O, respectively. The seal-breaking pressure was significantly greater in the PGA + alginate gel group than in the other groups (p < 0.01). There were no significant differences among the other three groups. Alginate gel combined with a PGA sheet is a promising alternative to fibrin glue as a safe and low-cost material for air leak prevention in pulmonary surgery.

Physical and biological properties of a novel anti-adhesion material made of thermally cross-linked gelatin film: Investigation of the usefulness as anti-adhesion material.

To create more useful, effective and safer anti-adhesion materials, we developed a thermally cross-linked gelatin film. In this study, we examined the physical properties of the film such as the physical strength and the adhesiveness to reveal the handling properties and biological properties, such as the anti-adhesion effect, the influence on cell proliferation, and the cytotoxicity to reveal the anti-adhesion mechanism, especially in comparison with the conventional hyaluronic acid and carboxymethylcellulose film (the conventional film). A tensile test under dry and wet conditions and shearing stress test showed that the gelatin film has significant higher maximum tensile stress and fracture strain than the conventional film. In the study using a rat model of cecum adhesion, the anti-adhesion effect of the gelatin film was significantly superior to that of the conventional film. In the cell proliferation test, the number of fibroblast cells on the gelatin film increased at each time point, while no cell proliferation was observed on the conventional film. Furthermore, in the cytotoxicity test using a colony assay and Live/Dead assay, the extract of the gelatin film had no cytotoxicity, while the extract of the conventional film had cytotoxicity considerably. These results suggest that the gelatin film provides better handling than the conventional film, due to better physical strength and ductility of the film. In addition, the gelatin film has a significantly greater anti-adhesion effect than the conventional film without any cytotoxicity. Therefore, the gelatin film is quite favorable as an anti-adhesion material. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 689-696, 2018.

Two-layer sheet of gelatin: A new topical hemostatic agent.

BACKGROUND/OBJECTIVE: Uncontrolled surgical bleeding is associated with increased morbidity, mortality, and hospital cost. Topical hemostatic agents available today have problems controlling hemostatic effects; furthermore, their handling is difficult and they are unsafe. METHODS: We devised a new hemostatic agent comprising gelatin sponge and film designed to be applied to the bleeding site, thereby creating a topical hemostatic agent made of gelatin alone. The gelatin was prepared by alkali treatment to eliminate viral activity. Hemostatic effects, surgical handling, and tissue reactions of the materials, namely a two-layer sheet of gelatin, TachoSil, and gelatin sponge, were evaluated using 21 dogs' spleens. RESULTS: The two-layer gelatin sheet and gelatin sponge exhibited superior hemostatic effects (100% hemostasis completed) compared with TachoSil (0-17% hemostasis). The gelatin matrix immediately absorbed blood flowing from wounds and activated the autologous components in the absorbed blood that promoted coagulation at the bleeding site. The two-layer gelatin sheet had the best surgical handling among the evaluated materials. Materials made of gelatin were associated with fewer inflammatory reactions compared with materials of TachoSil. CONCLUSION: The two-layer sheet of gelatin is a useful topical agent because of its superior hemostatic effects and usability, and is associated with a lower risk of transmitting diseases and inflammatory reactions.

The influences of a novel anti-adhesion device, thermally cross-linked gelatin film on peritoneal dissemination of tumor cells: The in vitro and in vivo experiments using murine carcinomatous peritonitis models.

To create anti-adhesive materials to be more effective and safer, we developed a thermally cross-linked gelatin film that showed superior anti-adhesive effects with excellent peritoneal regeneration. However, it may act as a convenient scaffold for tumor cell growth, thereby accelerating peritoneal dissemination when used in surgery for abdominal tumors. In this study, we tried to clarify this issue using mouse carcinomatous peritonitis models. First, we examined the in vitro tumor cell growth of mouse B16 melanoma or Colon26 cells on the gelatin film or the conventional hyarulonate/carboxymethylcellulose film. Tumor cell growth on each film was significantly lower than that of the control (no film). Next, we conducted the following in vivo experiments: After the parietal peritoneum was partially removed and covered with each film or without any film, mice were inoculated intraperitoneally with B16 melanoma or Colon26/Nluc cells expressing NanoLuc luciferase gene. At 7 days after the operation, we measured the weight of B16 melanoma tumors or the NanoLuc activity of Colon26/Nluc cells using in vivo imaging at the injured sites. There were no significant differences in the weight of the tumors and the NanoLuc activity among the three groups. We also observed the survival time of mice receiving the same operation and treatments. There was no significant difference in the survival time among the three groups. These results suggest that the gelatin film will likely not accelerate peritoneal dissemination as a convenient scaffold for tumor cell growth when used in surgery for abdominal tumors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2122-2130, 2018.

New polyglycolic acid fabric for the prevention of postoperative pancreatic fistulas.

BACKGROUND: The incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy is approximately 30%. The most serious complications of pancreatic resection, such as mortality and prolonged hospitalization, are unresolved despite the proposal of various surgical procedures. We developed a new polyglycolic acid (PGA) fabric composed of fine diameter fibers to prevent POPF, and macroscopically and microscopically evaluated the effects of applying it to the pancreatic remnant. METHODS: The ventral pancreatic surface was cauterized to create the experimental model of POPF in 33 female Wistar/ST rats. The injured sites were wrapped with nonwoven PGA fabrics of different fiber diameters and porosities in the treated rats; one group of rats remained untreated. Survival, incidence of generalized peritonitis, and microscopic findings around the pancreas were investigated. RESULTS: The PGA fabrics acted as a scaffold for tissue repair and resulted in superior survival. Generalized peritonitis was milder in the PGA treated groups. With the new PGA fabric, abundant fibroblast infiltration and a uniformly-developed, self-organized barrier wall prevented both pancreatic leak and spread of inflammation. CONCLUSION: Application of the newly developed PGA fabric to the pancreatic remnant prevented POPF, and the essential factor for preventing pancreatic leak was the early formation of a self-organized barrier.

Anti-adhesive effects of a newly developed two-layered gelatin sheet in dogs.

AIM: Adhesion after pelvic surgery causes infertility, ectopic pregnancy, and ileus or abdominal pain. The materials currently available for clinical use are insufficient. The purpose of this study was to develop an anti-adhesive material that overcomes the limitations of conventional anti-adhesive agents. METHODS: The adhesion prevention effects of three methods - a two-layered sheet composed of gelatin film and gelatin sponge, Seprafilm and INTERCEED - were evaluated in 37 dogs. Anti-adhesive effects were investigated macroscopically and microscopically in a cauterized uterus adhesion model. Cell growth on the materials in vitro using human peritoneal mesothelial cells, fibroblasts and uterine smooth muscle cells were also evaluated. RESULTS: The two-layered gelatin sheet had significantly superior anti-adhesive effects compared to the conventional materials (Seprafilm and INTERCEED). A single-cell layer of mature mesothelium formed three weeks after surgery in the gelatin group. Peritoneum regeneration in the Seprafilm and INTERCEED groups was delayed and incomplete in the early phase. Little inflammation around the materials occurred and cell growth was significantly proliferated with the gelatin sheet. CONCLUSION: The anti-adhesive effects of a two-layered gelatin sheet were superior to conventional agents in a cauterized canine uterus model, demonstrating early regeneration of the peritoneum, little inflammation and material endurance. The newly developed two-layered gelatin sheet is a useful option as an anti-adhesive agent for deeply injured and hemorrhagic sites.

Thermally Activated Delayed Fluorescence and Aggregation Induced Emission with Through-Space Charge Transfer.

Emissive molecules comprising a donor and an acceptor bridged by 9,9-dimethylxanthene, were studied (XPT, XCT, and XtBuCT). The structures position the donor and acceptor with cofacial alignment at distances of 3.3-3.5 Å wherein efficient spatial charge transfer can occur. The quantum yields were enhanced by excluding molecular oxygen and thermally activated delayed fluorescence with lifetimes on the order of microseconds was observed. Although the molecules displayed low quantum yields in solution, higher quantum yields were observed in the solid state. Crystal structures revealed π-π intramolecular interactions between a donor and an acceptor, however, the dominant intermolecular interactions were C-H···π, which likely restrict the molecular dynamics to create aggregation-induced enhanced emission. Organic light emitting devices using XPT and XtBuCT as dopants displayed electroluminescence external quantum efficiencies as high as 10%.

Prevention of Polyglycolic Acid-Induced Peritoneal Adhesions Using Alginate in a Rat Model.

Postoperative intra-abdominal or intrathoracic adhesions sometimes cause significant morbidity. We have designed three types of alginate-based treatments using strongly cross-linked (SL), weakly cross-linked (WL), and non-cross-linked (NL) alginate with calcium gluconate. In rat experiments, we compared the antiadhesive effects of the three types of alginate-based treatments, fibrin glue treatment (a standard treatment), and no treatment against adhesions caused by polyglycolic acid (PGA) mesh (PGA-induced adhesions). The antiadhesive materials were set on the PGA sheet fixed on the parietal peritoneum of the abdomen. Fifty-six days later, the adhesions were evaluated macroscopically by the adhesion scores and microscopically by hematoxylin-eosin staining and immunostaining. We also tested the fibroblast growth on the surface of the antiadhesive materials in vitro. The antiadhesive effects of WL and NL were superior to the no treatment and fibrin glue treatment. A microscopic evaluation confirmed that the PGA sheet was covered by a peritoneal layer constructed of well-differentiated mesothelial cells, and the inflammation was most improved in the NL and WL. The fibroblast growth was inhibited most on the surfaces of the NL and WL. These results suggest that either the WL or NL treatments are suitable for preventing PGA-induced adhesions compared to SL or the conventional treatment.

Biological properties of a thermally crosslinked gelatin film as a novel anti-adhesive material: Relationship between the biological properties and the extent of thermal crosslinking.

In order to prevent postoperative adhesion and the related complications, a thermally crosslinked gelatin (TCG) film was developed and the basic biological properties were examined, paying special attention to the relationship between these properties and the extent of crosslinking of the film. The gelatin films crosslinked thermally for five different time periods (0, 1, 3, 8, and 14 hours) were developed and the following tests were performed. Regarding the material characterization of the films, the water content, the water solubility, and the enzymatic degradation for collagenase were found to be closely related to the duration of thermal crosslinking. In an in vitro study conducted to examine the cell growth of fibroblasts cultured on the films, the degree of cell growth, except no crosslinked film, was less than that observed in the control group, thus suggesting that such effects of the films on fibroblast cell growth may be related with their anti-adhesive effects. In in vivo tests, the films crosslinked for longer time periods (3, 8, and 14 hours) were retained for longer after being implanted into the abdominal cavity in rats and showed a significant anti-adhesive effect in the rat cecum adhesion models, indicating that the biodegradability and anti-adhesive effects of the TCG films depend on the duration of thermal crosslinking. In order to develop useful and effective anti-adhesive gelatin film, it is very important to optimize duration of the thermal crosslinking.