Injectable, Shear-Thinning, Self-Healing, and Self-Cross-Linkable Benzaldehyde-Conjugated Chitosan Hydrogels as a Tissue Adhesive.

Benzaldehyde-conjugated chitosan (CH-CBA) was synthesized by a coupling reaction between chitosan (CH) and carboxybenzaldehyde (CBA). The pH-sensitive self-cross-linking can be achieved through the Schiff base reaction. The degree of substitution (DS) of CH-CBA was controlled at 1.4-12.7% by optimizing the pH and reagent stoichiometry. The dynamic Schiff base linkages conferred strong shear-thinning and self-healing properties to the hydrogels. The viscosity of the 2 wt/v % CH-CBA hydrogel decreased from 5.3 × 107 mPa·s at a shear rate of 10-2 s-1 to 2.0 × 103 mPa·s at 102 s-1 at pH 7.4. The CH-CBA hydrogel exhibited excellent biocompatibility in vitro and in vivo. Moreover, the hydrogel adhered strongly to porcine small intestine, colon, and cecum samples, comparable to commercial fibrin glue, and exhibited effective in vivo tissue sealing in a mouse cecal ligation and puncture model, highlighting its potential as a biomaterial for application in tissue adhesives, tissue engineering scaffolds, etc.

Dimensional changes of buccal bone in the edentulous maxilla with telescopic-retained implant-supported fixed dental prostheses.

STATEMENT OF PROBLEM: The buccal bone in an edentulous maxilla loses thickness over time because of physiological changes. However, the dimensional changes of the buccal bone in an edentulous maxilla with an implant-supported fixed dental prosthesis are unknown. PURPOSE: The purpose of this retrospective clinical study was to evaluate cone beam computed tomography (CBCT) images of the dimensional changes of the buccal bone in edentulous maxillae with complete arch telescopic-retained implant-supported fixed dental prostheses (CTI-FDPs) after 6 years by using a professional retrieval system. MATERIAL AND METHODS: This study included 17 participants with edentulous maxillae who had been provided with CTI-FDP with 121 taper joint implants. A three-dimensional radiographic analysis by using CBCT was performed at implant insertion (0 years) and after 6 years. Vertical and horizontal bone measurement values were evaluated. During horizontal bone thickness measurement, 4 different levels, 0, 2, 4, and 6 mm apical to the implant shoulder, were evaluated as bone value (BV)0mm, BV2mm, BV4mm, and BV6mm, respectively. The BVs were compared with the Wilcoxon signed-rank test and Kruskal-Wallis test (α=.05). In addition, the Spearman rank correlation coefficient was used to identify 0yBV factors that influence the 6yBVs. A nonlinear regression analysis was used to clarify the slopes of 0yBVs and 6yBV0mm. RESULTS: Significant decreases in vertical and horizontal BVs were found between 0 years and 6 years (P<.05). However, no significant difference was observed in bone loss at 6 years at any of the vertical and horizontal measurement points (P≥.05). When 0yBVs related to 6yBV0mm were analyzed, 0yBV0mm and 0yBV2mm showed strong correlations with 6yBV0mm (|r|≥.7). In the regression analysis, a 0yBV0mm of 0.58 mm and 0yBV2mm of 0.78 mm could be critical factors associated with a 6yBV0mm of 0 mm. A 6yBV0mm of 0yBV0mm more than 0.58 mm was significantly higher than a 6yBV0mm of 0yBV0mm less than 0.58 mm (P<.001). Moreover, a 6yBV0mm of 0yBV2mm more than 0.78 mm was significantly higher than a 6yBV0mm of 0yBV2mm less than 0.78 mm (P<.001). CONCLUSIONS: The buccal bone in an edentulous maxilla with fixed implant-supported prostheses lost significant vertical and horizontal bone thicknesses after 6 years. At implant insertion, both a 0.58-mm buccal bone on the platform and a 0.78-mm buccal bone at 2 mm apical to the implant shoulder are necessary for longer term maintenance of bone on the platform of implants specifically supporting CTI-FDPs.

Cisplatin-Chelated Iminodiacetic Acid-Conjugated Hyaluronic Acid Nanogels for the Treatment of Malignant Pleural Mesothelioma in Mice.

Malignant pleural mesothelioma (MPM) is one of the intractable cancers that require a more effective therapeutic strategy for clinical practice. Hyaluronic acid (HA) nanogels were prepared by the chelation of cisplatin (CDDP) with different molecular weights of iminodiacetic acid-conjugated hyaluronic acid (HA-IDA). The sizes of the 100, 850, and 2000 kDa HA nanogels were 33, 43, and 44 nm, respectively. MSTO-211H, a human MPM cell line, was more effective in taking up all three HA nanogels compared to AB22, a mouse MPM cell line. In addition, the 850 kDa HA nanogel showed higher anticancer activity against AB22 and MSTO-211H than 100 and 2000 kDa HA nanogels. Furthermore, all the HA nanogels showed a milder cytotoxic effect on normal Met-5A mesothelial cells compared to that exhibited by free CDDP. Finally, the 850 kDa HA nanogel was administrated intrapleurally into both the MSTO-211H xenograft and AB22 allograft mouse models of MPM using an injectable HA-based hydrogel. HA nanogels showed a significant therapeutic effect in both the xenograft and allograft models.

Implant Treatment in Patient with Periodontitis: A Case Report with 13-year Follow-up.

This report describes long-term implant treatment in a patient with chronic periodontitis. The patient was a 59-year-old man who attended our facility requesting a dental implant. An initial examination revealed generalized gingival inflammation and subgingival calculus. Clinical examination revealed 55.3% of sites with a probing depth (PD) of >4 mm and 41.3% of sites with bleeding on probing. Radiographic examination revealed vertical bone resorption in #23, #33, #33, #35, and #47. Initial periodontal therapy consisting of plaque control, scaling and root planing, and tooth extraction was subsequently performed based on a clinical diagnosis of severe chronic periodontitis. Open flap debridement was performed for teeth with a PD >5 mm (#21, #22, #23, 333, #34, #35 and #47). After confirming the stability of the periodontal tissue, 3 implants were first placed in the maxilla (#25, #26, and #27). Final prostheses comprising a screw retaining-type implant superstructure were then placed (#25, #26, and 327). Following reevaluation, the patient was placed on supportive periodontal therapy. At 15 years after the first visit, the periodontal and implant conditions have remained stable. These results indicate that periodontal treatment before implantation and subsequent maintenance yield a clinically favorable and long-lasting outcome.

Intraperitoneal Administration of a Cisplatin-Loaded Nanogel through a Hybrid System Containing an Alginic Acid-Based Nanogel and an In Situ Cross-Linkable Hydrogel for Peritoneal Dissemination of Ovarian Cancer.

Intraperitoneal chemotherapy demonstrates potential applicability in the treatment of peritoneally disseminated ovarian cancer because the disseminated tumors can directly receive exposure to high concentrations of anticancer drugs. However, a considerable proportion of drugs, particularly micromolecular and hydrophilic drugs, such as cisplatin (CDDP), are often excreted through glomerular filtration for a short period. To effectively deliver CDDP into peritoneally disseminated ovarian cancer tissues, we developed an alginate (AL)-based hybrid system in which a CDDP-loaded AL nanogel (AL/CDDP-nanogel) was encapsulated in an injectable AL-hydrogel cross-linked with calcium ions. This system enabled the sustained release of CDDP from the AL/CDDP-nanogel/AL-hydrogel hybrid for over a week. Herein, we constructed a peritoneally disseminated ovarian cancer mouse model using ovarian cancer cell lines with KRAS mutations (ID8-KRAS: KRASG12V). The AL/CDDP-nanogel/AL-hydrogel hybrid system showed significant antitumor activity in vivo. This therapy may be considered a novel strategy for the treatment of advanced-stage ovarian cancer with KRAS mutations.

Marginal bone loss and the risk indicators of fixed screw-retained implant-supported prostheses and fixed telescopic-retained implant-supported prostheses in full arch: A retrospective case-control study.

OBJECTIVES: This study compared full-arch screw-retained implant-supported fixed dental prostheses (FSI-FDPs) and full-arch telescopic-retained implant-supported fixed dental prostheses with a professional retrieval system (FTI-FDPs) on marginal bone loss (MBL), the risk indicators and peri-implantitis rate after 7-13 years. MATERIAL AND METHODS: Sixty five edentulous patients were treated with 86 prostheses and 592 implants. The FSI-FDP group comprised 26 patients (32 prostheses, 202 implants), and the FTI-FDP group comprised 39 patients (54 prostheses, 390 implants). MBL and the risk indicators of MBL ≥1 mm were assessed. Peri-implantitis rates at 13 years were also calculated. RESULTS: Full-arch screw-retained implant-supported fixed dental prostheses and FTI-FDP implants exhibited comparable mean MBLs of 0.60 ± 0.51 and 0.41 ± 1.03 mm, respectively. MBL ≥1 mm was noted for 25% of FSI-FDP implants and 6.9% of FTI-FDP implants. Superstructure-abutment connection (screw retention:FSI-FDPs >telescopic retention:FTI-FDPs) and implant-abutment connection (External butt joint, Internal butt joint >Morse taper joint) were associated with MBL ≥1 mm. Peri-implantitis rates at the implant level were 3.99% (95%CI = 3.93-20.5) in FSI-FDP group and 3.85% (95%CI = 3.85-34.3) in FTI-FDP group with no significance. CONCLUSIONS: It was concluded that FSI-FDP and FTI-FDP implants exhibited comparable MBL; however, the risk of MBL ≥1 mm in FTI-FDPs was lower than in FSI-FDPs. Besides, implant-abutment connection was the risk indicator of MBL ≥1 mm. In peri-implantitis rate, FSI-FDPs and FTI-FDPs behave similarly.

Implant Body Displacement into Medullary Cavity of Mandible: A Case Report.

One serious complication in implant surgery is displacement of the implant body into the surrounding tissue. This occurs only rarely in the mandible, however. This report describes a case of an implant body displacing into the medullary cavity of the mandible and discusses this in reference to the literature. The patient was a 72-year-old woman who was referred to our department at Tokyo Dental College Chiba Hospital (now Chiba Dental Center) by her regular dentist after an implant inserted in the left mandible in 2010 showed loosening in October 2016. Panoramic X-rays obtained at the initial examination revealed that 2 implants had been inserted into the left mandible, one on top of the other. Removal of both was recommended to prevent infection at the implant site and any potential effects on the alveolar nerve. In the absence of subjective symptoms other than implant loosening, however, the patient did not consent to this proposal. Therefore, only the broken abutment was removed. The patient was instructed to contact us immediately should infection or any other symptoms appear once the mucosa had healed, and the dental clinic that had referred her to us was requested to make her a set of dentures. To our knowledge, only 11 reports have been published to date describing displacement of an implant body into the mandible, and these address a total of just 20 cases. The possibility that an implant body in the mandible may become displaced must be kept in mind during treatment.

Size-Controlled Preparation of Microsized Perfluorocarbon Emulsions as Oxygen Carriers via the Shirasu Porous Glass Membrane Emulsification Technique.

We have developed microsized perfluorocarbon (PFC) emulsions with different sizes as artificial oxygen carriers (OCs) via Shirasu porous glass membrane emulsification. Monodispersed PFC emulsions with narrow size distribution were obtained. By changing the membrane pore size, we were able to precisely control the size of emulsions and fabricate emulsions similar in size to human red blood cells. Behaviors of Pluronics with different physiochemical properties (F127, F68, P85, and P103) as surfactants were also investigated, which evidenced that the type and concentration of Pluronics have a major impact on the size of emulsions and the response to different thermal conditions. The F127-stabilized microsized PFC emulsions were stable even during autoclave sterilization. The emulsions were loaded with Ru(ddp)-an oxygen-sensitive probe-on their surfaces to indicate oxygen concentration. Finally, incubations with HeLa cells that show fluorescence in response to hypoxia cultured in 2D and 3D suggested promising potential of our emulsions for OCs.

Clinical evaluation of full-arch screw-retained implant-supported fixed prostheses and full-arch telescopic-retained implant-supported fixed prostheses: A 5-12 year follow-up retrospective study.

OBJECTIVE: To assess the prostheses and implants survival rate and peri-implantitis rate in edentulous patients treated with full-arch screw-retained implant-supported fixed dental prostheses (FSIFDPs) and full-arch telescopic-retained implant-supported fixed dental prostheses (FTIFDPs) over an observation period of at least 5 years. MATERIALS AND METHODS: From 2004 to 2012, 696 implants were inserted into 78 patients with 102 prostheses. The FSIFDP group comprised 31 patients (37 prostheses, 232 implants), whereas the FTIFDP group comprised 47 patients (65 prostheses, 464 implants). Prosthesis and implant estimated cumulative survival rates (ECSR) and estimated cumulative peri-implantitis rates (ECPR) were assessed. The follow-up period was 5-12 years. Kaplan-Meier survival curves with the log-rank test were used to evaluate outcomes. RESULTS: The 12-year prosthesis ECSR was 96.8% (95% CI: 79.2-99.5, 36/37 prostheses) in the FSIFDP group and 96.4% (95% CI: 86.3-99.1, 63/65 prostheses) in the FTIFDP group, whereas the 12-year implant ECSR was 99.5% (95% CI: 96.4-99.9, 231/232 implants) in the FSIFDP group and 98.7% (95% CI: 96.9-99.5, 459/464 implants) in the FTIFDP group. The 12-year ECPR at the prosthesis level was 12.8% (95% CI: 12.7-47.6, 4/37 prostheses) in the FSIFDP group and 12.8% (95% CI: 11.4-24.1, 6/65 prostheses) in the FTIFDP group. The 12-year ECPR at the implant level was 4.4% (95% CI: 4.3-23.0, 6/232 implants) in the FSIFDP group and 2.2% (95% CI: 2.0-12.3, 7/464 implants) in the FTIFDP group. CONCLUSION: FTIFDPs have clinical results comparable to those of FSIFDPs. Therefore, FTIFDPs can be useful.

Role of Dental Implant Superstructure in Patients with Severe Periodontal Disease.

Many studies have investigated the relationship between periodontal disease and the onset of peri-implantitis. It is important to devise practical measures for preventing the development of peri-implantitis in patients with periodontal disease if the success of implant treatment is to be secured. Here, we report the role of the superstructure in two cases of implant treatment in patients with severe periodontal disease. Both patients had severe periodontitis and underwent implant treatment after improving the state of the disease, thereby ensuring that the implant superstructure could be maintained. Both cases remained stable after implant treatment. The results indicate that proper periodontal treatment prior to implant treatment leads to long-term success. In addition, it is necessary to use an implant superstructure that reduces plaque accumulation in preventing peri-implantitis.

Implant-supported Prostheses in Patient with Sjögren's Syndrome: Clinical Report with 3-year Follow-up.

Sjögren's syndrome (SS), an autoimmune disorder, affects the exocrine glands, including the lacrimal and salivary glands. It is characterized by symptoms of dry eye and dry mouth. As secretion of saliva decreases, patients with SS experience rampant caries, pain in the oral mucosa, inflammation and hardening of the salivary glands, abnormal taste, dysphagia, and loss of teeth earlier than healthy individuals. A removable partial denture is often used as a prosthesis after tooth loss. Compromised salivary lubrication, however, can produce traumatic ulceration of the mucosa, making use of a removable prosthesis in SS patients painful. In such cases, a dental implant is likely to be requested as an alternative. This report describes dental implant treatment in an SS patient, a 50-year-old woman who presented with the chief complaint of masticatory dysfunction and pain due to a removable partial denture. Eight implants were placed in the maxillary and mandibular first molar tooth and second molar tooth regions. Following a 4-month non-loading period, second-stage surgery and provisional restoration with a screwretained implant temporary crown were performed. Screw-retained superstructures were fitted by means of a customized titanium abutment and zirconia crown as the final restoration. No complications, including inflammation of peri-implant soft tissue or resorption of peri-implant bone, were observed at 3 years following placement of the superstructures.

Implant Treatment after Sagittal Splitting Ramus Osteotomy and Alveolar Ridge Augmentation in Patient with Mandibular Prognathism and Multiple Missing Maxillary Teeth.

An abnormal maxillomandibular ridge relationship frequently hinders oral implant treatment in patients with jaw deformities. Here, we describe a patient who was experiencing difficulty using dentures due to multiple maxillary tooth loss and mandibular prognathism. Treatment comprising sagittal splitting ramus osteotomy and alveolar ridge augmentation using bone grafts harvested from the mandibular ramus followed by implant treatment yielded good outcomes. The patient was a 47-year-old woman presenting with an unstable upper partial denture. Although prior prosthetic treatment for mandibular prognathism had resulted in normal overbite, she had since lost an increasing number of teeth due to advanced periodontal disease, impairing support for the denture. She was referred to the Department of Oral Implantology at the Tokyo Dental College Chiba Hospital in October 2008. Subsequent treatment comprised implant treatment following maxillary alveolar ridge augmentation and sagittal splitting ramus osteotomy to correct the maxillary-mandibular relationship. In January 2010, sagittal splitting ramus osteotomy and alveolar bone augmentation using a bone graft from the mandibular ramus were performed under general anesthesia. In July and August 2010, a total of 7 implants were placed in the maxilla and implant superstructure preparation started after 3 months. Taking both the patient's wishes and ease of maintenance into account, retrievable superstructures made of Auro Galvano Crown were fitted in April 2011. The jaw-to-jaw alveolar ridge relationship was improved by sagittal splitting ramus osteotomy, rendering subsequent treatment, from implant placement to superstructure preparation, feasible by conventional methods. The use of surplus bone generated during sagittal splitting ramus osteotomy for bone augmentation avoided the need to harvest bone from another area.

Intraperitoneal Delivery of Cisplatin via a Hyaluronan-Based Nanogel/in Situ Cross-Linkable Hydrogel Hybrid System for Peritoneal Dissemination of Gastric Cancer.

Intraperitoneal administration of chemotherapeutics is expected for the treatment of peritoneally disseminated gastric cancer because of poor migration of the drugs from the systemic circulation to the peritoneal cavity. In this study, for intraperitoneal delivery of cisplatin (CDDP), we developed a hyaluronan (HA)-based hybrid system in which CDDP-loaded HA nanogels were either physically encapsulated in or chemically conjugated to injectable HA hydrogels. Physical encapsulation enabled sustained release of HA nanogels from the HA hydrogel matrix for over a week. This was a longer release period than that of encapsulated free CDDP, which released 80% of the drug in 2 days. The longer release was attributed to delayed diffusion of HA nanogels from the hydrogel matrix network. The release profile could be tuned by modifying the chemical conjugation of HA nanogels to the HA hydrogel matrix, as well as the type of chelating ligands used to load CDDP to the nanogel. Furthermore, intraperitoneally administered hybrid had significant antitumor activity in a mouse model of peritoneally disseminated gastric cancer, especially for nodules smaller than 1.0 mm.

Current State of Undergraduate Education in Oral Implantology in Japan.

An anonymous questionnaire-based survey was used to determine the current state of and issues involved in undergraduate education in oral implantology at Tokyo Dental College. The participants comprised 139 students who had received lectures on and practical training in oral implantology in 2013. The results indicate that the overall level of student comprehension was high for both lectures and practical training content; the level of difficulty was appropriate for practical training, but the amount of practice time given requires reconsideration. Over 80% of the students gave positive responses in their overall evaluation of lectures and practical training, and the number of students who had an interest in oral implantology after finishing the course and who wanted to be involved in oral implantology as dentists increased. These results indicate that this undergraduate education program is effective in improving understanding of oral implantology. Improvement is required, however, in lecture methodology and practical training content. It is also suggested that the curriculum should be evaluated by students regularly and that the courses be subject to updating as required.

Clinical evaluation of salivary periodontal pathogen levels by real-time polymerase chain reaction in patients before dental implant treatment.

OBJECTIVE: Periodontal pathogens in dental plaque are the main causative agents of periodontitis and peri-implantitis. Detection of the presence of such periodontal pathogens early would serve as a useful tool in the diagnosis and treatment of this disease. Therefore, the purpose of this study was to investigate whether the periodontal pathogen levels in saliva were correlated with the periodontal status of patients receiving implant treatment. MATERIALS AND METHODS: A total of 291 patients visiting Tokyo Dental College Chiba Hospital were divided into four groups: a no-periodontitis (np) group, a mild-periodontitis (mip) group, a moderate-periodontitis (mop) group, and a severe-periodontitis (sp) group. The levels of the following five periodontal pathogens in saliva were evaluated using real-time polymerase chain reaction: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Prevotella intermedia. RESULTS: The levels of P. gingivalis and T. forsythia were significantly higher in mop group than in np group (P < 0.05). The levels of all periodontal pathogens tested except A. actinomycetemcomitans were significantly higher in sp group than in np group (P < 0.05). CONCLUSION: The detection levels of the periodontal pathogens targeted in saliva samples were correlated with the periodontal status. This suggests that using saliva to screen for periodontopathic bacteria offers an easier-to-use clinical tool than the paper point method in the diagnosis and treatment of periodontitis and peri-implantitis.

Intraperitoneal administration of cisplatin via an in situ cross-linkable hyaluronic acid-based hydrogel for peritoneal dissemination of gastric cancer.

PURPOSE: To develop a drug-delivery system for the prolonged retention of intraperitoneally (i.p.) administered cisplatin (CDDP) to deliver intraperitoneal chemotherapy against peritoneal carcinomatosis effectively. METHODS: CDDP was encapsulated inside an in situ cross-linkable hyaluronic acid (HA)-based hydrogel. The gelation and degradation kinetics of the hydrogel and the release kinetics of CDDP were investigated in vitro, and the antitumor effect was investigated in a mouse model of peritoneal dissemination of human gastric cancer. RESULTS: The gelation time varied according to the concentration of two polymers: HA-adipic dihydrazide and HA-aldehyde. CDDP was released from the hydrogel for more than 4 days. A cell proliferation assay showed that the polymers themselves were not cytotoxic toward MKN45P, a human gastric cancer cell line. By mixing the two polymers in the peritoneum, in situ gelation was achieved. The weight of peritoneal nodules decreased in the hydrogel-conjugated CDDP group, whereas no significant antitumor effect was observed in the free CDDP group. CONCLUSIONS: In situ cross-linkable HA hydrogels represent a promising biomaterial to prolong the retention and sustain the release of intraperitoneally administered CDDP in the peritoneal cavity and to enhance its antitumor effects against peritoneal dissemination.

Moldable Tissue-Sealant Hydrogels Composed of In Situ Cross-Linkable Polyethylene Glycol via Thiol-Michael Addition and Carbomers.

Moldable tissue-sealant hydrogels were developed herein by combining the yield stress fluidity of a Carbomer and in situ cross-linking of 3-arm PEG-thiol (PEG-SH) and 4-arm PEG-acrylate (PEG-AC). The Carbomer was mixed with each PEG oligomer to form two aqueous precursors: Carbomer/PEG-SH and Carbomer/PEG-AC. The two hydrogel precursors exhibited sufficient yield stress (>100 Pa) to prevent dripping from their placement on the tissue surface. Moreover, these hydrogel precursors exhibited rapid restructuring when the shear strain was repeatedly changed. These rheological properties contribute to the moldability of these hydrogel precursors. After mixing these two precursors, they were converted from yield-stress fluids to chemically cross-linked hydrogels, Carbomer/PEG hydrogel, via thiol-Michael addition. The gelation time was 5.0 and 11.2 min at 37 and 25 °C, respectively. In addition, the Carbomer/PEG hydrogels exhibited higher cellular viability than the pure Carbomer. They also showed stable adhesiveness and burst pressure resistance to various tissues, such as the skin, stomach, colon, and cecum of pigs. The hydrogels showed excellent tissue sealing in a cecum ligation and puncture model in mice and improved the survival rate due to their tissue adhesiveness and biocompatibility. The Carbomer/PEG hydrogel is a potential biocompatible tissue sealant that surgeons can mold. It was revealed that the combination of in situ cross-linkable PEG oligomers and yield stress fluid such as Carbomer is effective for developing the moldable tissue sealant without dripping of its hydrogel precursors.

Hepatocyte Growth Factor DNA Aptamer for Prevention of Postoperative Peritoneal Adhesion via Enhancement of Fibrinolysis and Inhibition of Mesothelial Mesenchymal Transition.

Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery, posing a significant hindrance to postsurgical recovery. Although several strategies have been developed to alleviate and prevent adhesions, their efficacy remains unsatisfactory. For the first time, we studied the therapeutic effect and mechanism of our recently developed thermally stable oligonucleotide-based mimetics of hepatocyte growth factor (HGF DNA aptamer) to prevent PPA. The HGF DNA aptamer effectively inhibited canonical TGF-ß1 signaling transduction, partially suppressing mesothelial mesenchymal transition. Additionally, the aptamer, respectively, upregulated and downregulated the expression of tissue plasminogen activator and plasminogen activator inhibitor 1, thereby enhancing fibrinolytic activity. As a pleiotropic factor, the HGF DNA aptamer also enhanced the migratory and proliferative capacities of mesothelial cells. Finally, the aptamer demonstrated a higher level of effectiveness in preventing PPAs than the commercially available antiperitoneal adhesion barrier, Seprafilm. Due to its therapeutic benefits, excellent stability, biosafety, cost-effectiveness, and versatility, the HGF DNA aptamer demonstrates promise for preventing PPA in future clinical settings.

Injectable, shear-thinning, photocrosslinkable, and tissue-adhesive hydrogels composed of diazirine-modified hyaluronan and dendritic polyethyleneimine.

In the present study, we report the first synthesis of diazirine-modified hyaluronic acid (HA-DAZ). In addition, we also produced a precursor polymer solution composed of HA-DAZ and dendritic polyethyleneimine (DPI) that showed strong shear-thinning properties. Furthermore, its viscosity was strongly reduced (i.e., from 5 × 105 mPa s at 10-3 s-1 to 6 × 101 mPa s at 103 s-1), substantially, which enhanced solution injectability using a 21 G needle. After ultraviolet irradiation at 365 nm and 6 mW cm-2, the HA-DAZ/DPI solution achieved rapid gelation, as measured using the stirring method, and its gelation time decreased from 200 s to 9 s as the total concentrations of HA-DAZ and DPI increased. Following UV irradiation, the storage modulus increased from 40 to 200 Pa. In addition, reversible sol-gel transition and self-healing properties were observed even after UV irradiation. This suggests that the HA-DAZ/DPI hydrogel was crosslinked in multiple ways, i.e., via covalent bonding between the diazirine and amine groups and via intermolecular interactions, including hydrogen bonding, electrostatic interactions, and hydrophobic interactions. A lap shear test showed that the HA-DAZ/DPI hydrogel exhibited strong adhesiveness as a fibrin glue following UV irradiation. Finally, the HA-DAZ/DPI hydrogel showed higher tissue reinforcement than fibrin glue in an ex vivo burst pressure test of the porcine esophageal mucosa.

In situ cross-linkable hydrogel of hyaluronan produced via copper-free click chemistry.

Injectable hydrogels are useful in biomedical applications. We have synthesized hyaluronic acids chemically modified with azide groups (HA-A) and cyclooctyne groups (HA-C), respectively. Aqueous HA-A and HA-C solutions were mixed using a double-barreled syringe to form a hydrogel via strain-promoted [3 + 2] cycloaddition without any catalyst at physiological conditions. The hydrogel slowly degraded in PBS over 2 weeks, which was accelerated to 9 days by hyaluronidase, while it rapidly degraded in a cell culture media with fetal bovine serum within 4 days. Both HA-A and HA-C showed good biocompatibility with fibroblast cells in vitro. They were administered using the double-barreled syringe into mice subcutaneously and intraperitoneally. Residue of the hydrogel was cleared 21 days after subcutaneous administration, while it was cleared 7 days after intraperitoneal administration. This injectable HA hydrogel is expected to be useful for tissue engineering and drug delivery systems utilizing its orthogonality.