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Sprayable nanomicelle hydrogels and inflammatory bowel disease patient cell chips for development of intestinal lesion-specific therapy.
Yoon, Hyo-Jin; Lee, Songhyun; Kim, Tae Young; Yu, Seung Eun; Kim, Hye-Seon; Chung, Young Shin; Chung, Seyong; Park, Suji; Shin, Yong Cheol; Wang, Eun Kyung; Noh, Jihye; Kim, Hyun Jung; Ku, Cheol Ryong; Koh, Hong; Kim, Chang-Soo; Park, Joon-Sang; Shin, Young Min; Sung, Hak-Joon.
Afiliação
  • Yoon HJ; Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Lee S; Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Kim TY; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea.
  • Yu SE; Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Kim HS; School of Electrical and Electronic Engineering, Yonsei University, Seoul, 03722, Republic of Korea.
  • Chung YS; Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Chung S; Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Park S; Department of Obstetrics and Gynecology, Institution of Women's Life Medical Science, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Shin YC; Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Wang EK; Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Noh J; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
  • Kim HJ; Department of Internal Medicine, Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Ku CR; Department of Pediatrics, Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Koh H; Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Kim CS; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
  • Park JS; Department of Internal Medicine, Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Shin YM; Department of Pediatrics, Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • Sung HJ; Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Bioact Mater ; 18: 433-445, 2022 Dec.
Article em En | MEDLINE | ID: mdl-35415304
ABSTRACT
All-in-one treatments represent a paradigm shift in future medicine. For example, inflammatory bowel disease (IBD) is mainly diagnosed by endoscopy, which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels. Furthermore, molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy. This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component. These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy. Next, peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions, specifically by nanomicelles. The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation. Hence, the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5 (TLR5) as the main target of flagellin binding and Notch-1. The peptide binding potently suppressed inflammatory signaling without drug loading, where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha. The results were produced using a human colorectal cell line, clinical IBD patient cells, gut-on-a-chip, a mouse IBD model, and pig experiments to validate the translational utility.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article