Development of new biodegradable hydrogel glue for preventing alveolar air leakage Masato Araki, MD, Hiroyuki Tao, MD, PhD, Naoki Nakajima, PhD, Hajime.

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Development of new biodegradable hydrogel glue for preventing alveolar air leakage Masato Araki, MD, Hiroyuki Tao, MD, PhD, Naoki Nakajima, PhD, Hajime Sugai, BEng, Toshihiko Sato, MD, Suong-Hyu Hyon, PhD, Takeshi Nagayasu, MD, PhD, Tatsuo Nakamura, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 134, Issue 5, Pages 1241-1248 (November 2007) DOI: 10.1016/j.jtcvs.2007.07.020 Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Chemical structure and appearance of new-glue. New-glue is composed of two solutions of aldehyded dextran and ε-poly(l-lysine) (A). After the two solutions are mixed, gel formation proceeds on the basis of Schiff base formation. An equal volume of each solution is stored in the separate cylinders of a dual syringe device at 4°C until use (B). The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1241-1248DOI: (10.1016/j.jtcvs.2007.07.020) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Pleuroparenchymal defects for evaluation of glue sealing effect and histotoxicity. Large pleuroparenchymal defects (30 × 30-mm square, 1-mm deep) were created with scalpels and electrocautery for the evaluation of sealing effect (A). Circular pleuroparenchymal defects (15 mm in diameter) were created with scalpels, and hemostasis was obtained by pressure with a sponge for evaluation of histotoxicity (B). The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1241-1248DOI: (10.1016/j.jtcvs.2007.07.020) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Bursting pressure before and after application of new-glue and fibrin glue. There were no significant differences in mean air leakage pressure after creating the pleuroparenchymal defects (P = .82). After application, new-glue showed better sealing effect than fibrin glue (P = .02). The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1241-1248DOI: (10.1016/j.jtcvs.2007.07.020) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Macroscopic and histologic appearance at 1 hour and 2 and 4 weeks after application of new-glue. New-glue, which was dyed blue, was rubbed on the defect area (A) and penetrated into the deep lung parenchyma (B). At 2 weeks, the glue had turned brown, owing to the Maillard reaction, and was covered by a thin white membrane (C), consisting of one layer of mesothelial cells. Foreign body giant cells and fibroblasts were observed around the glue (D). At 4 weeks, the glue was still evident (E) and was completely covered by thick fibrous tissue (F) (hematoxylin and eosin stain; original magnification × 100; scale bar shows 200 μm). The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1241-1248DOI: (10.1016/j.jtcvs.2007.07.020) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Macroscopic and histologic appearance 2, 3, and 6 months after application of new-glue. At 2 months, new-glue had considerably lightened (A), and inflammatory reactions around it were slight (B). At 3 months, about 90% of the glue had degraded (C), and scattered fragments of residual glue were evident (D). By 6 months, complete disappearance of the glue had not occurred (E), and no inflammatory reaction was observed around the slight amount of residual glue (F) (hematoxylin and eosin stain; original magnification × 100; scale bar shows 200 μm). The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1241-1248DOI: (10.1016/j.jtcvs.2007.07.020) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 Macroscopic and histologic appearance at 1 hour and 2 and 4 weeks after application of fibrin glue. Fibrin glue was applied by the rubbing and spraying method (A) and penetrated into the lung parenchyma (B). At 2 weeks, glue with a whitish appearance was clearly evident at the center of the application area (C) and was encapsulated by a thick fibrocellular layer. Infiltration of lymphocytes and fibroblasts was observed around the glue (D). At 4 weeks, the application area was covered by whitish colored pleura (E), which was thickened with fibrous tissue and slight infiltration of lymphocytes (F) (hematoxylin and eosin stain; original magnification × 100; scale bar shows 200 μm). The Journal of Thoracic and Cardiovascular Surgery 2007 134, 1241-1248DOI: (10.1016/j.jtcvs.2007.07.020) Copyright © 2007 The American Association for Thoracic Surgery Terms and Conditions