Event Abstract Back to Event Fabrication of biodegradable multi-layered nanosheets to reinforce the bursting strength and maintain high adhesiveness for a wound dressing in partial hepatectomy Yosuke Okamura1, Takuya Komachi1, Hideaki Sumiyoshi2, Yutaka Inagaki2, Shinji Takeoka3 and Yu Nagase1 1 Tokai University, Course of Industrial Chemistry, Graduate School of Engineering, Japan 2 Tokai University School of Medicine, Department of Regenerative Medicine, Japan 3 Waseda University, Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Japan Introduction: We have proposed free-standing biodegradable nanosheets composed of poly (L-lactic acid) (PLLA) for biomedical applications[1]. The nanosheets with a thickness of less than 100 nm exhibit unique properties such as high adhesiveness and exquisite flexibility[1]. In fact, they can be adhered to moist organs without any adhesive agents. Recently, we demonstrated that the nanosheets acted as an effective wound dressing in a gastric operations in mice[1]. However, they burst easily due to their nano-thickness. In this paper, we propose PLLA nanosheets with multi-layer structure inside. We expected the high adhesiveness of the nanosheet would be maintained by controlling each layers to nano-thickness, and its resistance to bursting would be reinforced by the multi-layer structure. Moreover, we evaluated whether the multi-layered nanosheets act as hemostats in partial hepatectomy, which is an appropriate in vivo system to test both functions (the resistance to bursting and the adhesiveness). Materials and Methods: The multi-layering of sodium alginate (Na-Alg, 20 mg/mL) and PLLA (10 mg/mL) was repeated 3-10 times by multiple rounds of spin-coating (4,000 rpm, 20 s) on a SiO2 substrate (Fig. 1A). The substrate was immersed in an aqueous solution of 20 mg/mL CaCl2 to allow gelation of the Na-Alg layers between PLLA nanosheets. The composite film was released from the substrate into water. Only two sides of the film was fusion-cut sealed with a Poly sealer® (Fuji Impulse, Japan) at 187oC. The sealed film was incubated in EDTA to remove alginate layers. After washing with water, the multi-layered nanosheets were obtained. The bursting pressure and adhesive strength of the nanosheets were measured by a micro-scratch tester and a custom-made bursting tester. In a partial hepatectomy rat model, the 5-layered nanosheet supported with PVA film was sealed on the incised liver (size: 10 mm). Blood loss just after the sealing was measured for 5 min. As negative and positive controls, only PVA film and clinically-used TachoSil® were tested. Results and Discussion: The multi-layered nanosheets were fabricated by simple combination procedures: (i) multi-layering of PLLA and alginate, (ii) gelation of the alginate layers, (iii) fusion-cut sealing and (iv) elution of alginate layers (Fig. 1A). The multi-layered nanosheet was very flexible structure, which appeared whitish due to internal multi-layers (Fig. 1B). Moreover, they exhibited an effective configuration to reinforce the bursting strength in parallel with the number of layers, and their adhesive strength were maintained at a high level as expected. In fact, the multi-layered nanosheets were found to be a potential to act as a novel wound dressing for hemostats (Fig. 2, blood loss of 5-layered nanosheet, only PVA film, and TachoSil: 0.65±0.12, 2.60±0.20, and 0.94±0.17 g, respectively), and they tended to show reduced tissue adhesion. Conclusion: The free-standing multi-layered nanosheet composed of PLLA would be an ideal candidate for an alternative to conventional therapy in hepatectomy and other operations accompanied by bleeding. Research Activity Start-up (24800063) from the Japan Society for the Promotion of Science (JSPS)
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Jan 1, 2016
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