A multicenter, prospective, randomized clinical trial of marine mussel-inspired adhesive hemostatic materials, InnoSEAL Plus

Purpose@#InnoSEAL Plus is an adhesive, coagulant-free hemostatic material that mimics the adhesion mechanism of marine mussels. This study reports on the safety and efficacy of InnoSEAL Plus for patients with hemorrhage after hepatectomy despite first-line hemostasis treatments. @*Methods@#This is a multicenter, prospective, single-blinded, randomized clinical trial involving 96 hepatectomy patients. TachoSil was used as a comparator group. Three-minute and 10-minute hemostatic success rates were monitored. Rebleeding rates were also observed. Safety was assessed by recording all novel undesirable symptoms. @*Results@#InnoSEAL Plus showed a 3-minute hemostasis rate of 100%, while TachoSil had a rate of 98.0% (48 of 49 patients), demonstrating that the 2 had similar hemostatic efficacies. The difference in efficacy between the test and comparator group was 2.04%, and the lower limit of the one-sided 97.5% confidence interval was –1.92%; as this is greater than the noninferiority limit of –23.9%, the 2 treatments were equivalent. Meanwhile, the 10-minute hemostatic success rate was the same in both groups (100%). No rebleeding occurred in either group. In the safety evaluation, 89 patients experienced adverse events (45 in the test group and 44 in the comparator group). The difference between the 2 groups was not significant. No death occurred after application of the test or comparator group product. @*Conclusion@#Given that InnoSEAL Plus is a coagulation factor-free product, the hemostasis results are encouraging, especially considering that TachoSil contains a coagulation factor. InnoSEAL Plus was found to be a safe and effective hemostatic material for control of bleeding in hepatectomy patients.

Novel Fabrication of MicroRNA Nanoparticle-Coated Coronary Stent for Prevention of Post-Angioplasty Restenosis

BACKGROUND AND OBJECTIVES: MicroRNA 145 is known to be responsible for cellular proliferation, and its enhanced expression reportedly inhibits the retardation of vascular smooth muscle cell growth specifically. In this study, we developed a microRNA 145 nanoparticle immobilized, hyaluronic acid (HA)-coated stent. MATERIALS AND METHODS: For the gene therapy, we used disulfide cross-linked low molecular polyethylenimine as the carrier. The microRNA 145 was labeled with YOYO-1 and the fluorescent microscopy images were obtained. The release of microRNA 145 from the stent was measured with an ultra violet spectrophotometer. The downstream targeting of the c-Myc protein and green fluorescent protein was determined by Western blotting. Finally, we deployed microRNA 145/ssPEI nanoparticles immobilized on HA-coated stents in the balloon-injured external iliac artery in a rabbit restenosis model. RESULTS: Cellular viability of the nanoparticle-immobilized surface tested using A10 vascular smooth muscle cells showed that MSN exhibited negligible cytotoxicity. In addition, microRNA 145 and downstream signaling proteins were identified by western blots with smooth muscle cell (SMC) lysates from the transfected A10 cell, as the molecular mechanism for decreased SMC proliferation that results in the inhibition of in-stent restenosis. MicroRNA 145 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis at the post-implantation. We investigated the qualitative analyses of in-stent restenosis in the rabbit model using micro-computed tomography imaging and histological staining. CONCLUSION: MicroRNA 145-eluting stent mitigated in-stent restenosis efficiently with no side effects and can be considered a successful substitute to the current drug-eluting stent.

Development of animal experimental periodontitis models

PURPOSE: An animal periodontitis model is essential for research on the pathogenesis and treatment of periodontal disease. In this study, we have introduced a lipopolysaccharide (LPS) of a periodontal pathogen to the alveolar bone defect of experimental animals and investigated its suitability as a periodontitis model. METHODS: Alveolar bone defects were made in both sides of the mandibular third premolar region of nine beagle dogs. Then, the animals were divided into the following groups: silk ligature tied on the cervical region of tooth group, Porphyromonas gingivalis LPS (P.g. LPS)-saturated collagen with silk ligature group, and no ligature or P.g. LPS application group as the control. The plaque index and gingival index were measured at 0 and 4 weeks postoperatively. The animals were then euthanized and prepared for histologic evaluation. RESULTS: The silk ligature group and P.g. LPS with silk ligature group showed a significantly higher plaque index at 4 weeks compared to the control (P<0.05). No significant difference was found in the plaque index between the silk ligature group and P.g. LPS with silk ligature group. The P.g. LPS with silk ligature group showed a significantly higher gingival index compared to the silk ligature group or the control at 4 weeks (P<0.05). Histologic examination presented increased inflammatory cell infiltration in the gingival tissue and alveolar bone of the P.g. LPS with silk ligature group. CONCLUSIONS: An additional P.g. LPS-saturated collagen with silk ligature ensured periodontal inflammation at 4 weeks. Therefore, P.g. LPS with silk ligature application to surgically created alveolar bone defects may be a candidate model for experimental periodontitis.