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Abstract
Highlights
A series of novel injectable pH-responsive self-healing hydrogels with enhanced adhesive strength were prepared.
The hydrogels showed good gastric hemostasis property in a swine gastric hemorrhage model.
The hydrogels greatly enhanced gastric wound healing in a swine gastric wound model.
Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are well-established therapeutics for gastrointestinal neoplasias, but complications after EMR/ESD, including bleeding and perforation, result in additional treatment morbidity and even threaten the lives of patients. Thus, designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge. Herein, a series of injectable pH-responsive self-healing adhesive hydrogels based on acryloyl-6-aminocaproic acid (AA) and AA-g-N-hydroxysuccinimide (AA-NHS) were developed, and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model. The hydrogels showed a suitable gelation time, an autonomous and efficient self-healing capacity, hemostatic properties, and good biocompatibility. With the introduction of AA-NHS as a micro-cross-linker, the hydrogels exhibited enhanced adhesive strength. A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding. A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition, α-SMA expression, and blood vessel formation. These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.
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Details
1 The First Affiliated Hospital of Xi’an Jiaotong University, Department of Gastroenterology, Xi’an, People’s Republic of China (GRID:grid.452438.c); Xi’an Jiaotong University, Frontier Institute of Science and Technology, and State Key Laboratory for Mechanical Behavior of Materials, Xi’an, China (GRID:grid.43169.39) (ISNI:0000 0001 0599 1243); Xi’an Jiaotong University, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an, People’s Republic of China (GRID:grid.43169.39) (ISNI:0000 0001 0599 1243)
2 The First Affiliated Hospital of Xi’an Jiaotong University, Department of Gastroenterology, Xi’an, People’s Republic of China (GRID:grid.452438.c); Xi’an Jiaotong University, Frontier Institute of Science and Technology, and State Key Laboratory for Mechanical Behavior of Materials, Xi’an, China (GRID:grid.43169.39) (ISNI:0000 0001 0599 1243); Xi’an Jiaotong University, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an, People’s Republic of China (GRID:grid.43169.39) (ISNI:0000 0001 0599 1243); The First Affiliated Hospital of Xi’an Jiaotong University, Department of Dermatology, Xi’an, People’s Republic of China (GRID:grid.452438.c)
3 The First Affiliated Hospital of Xi’an Jiaotong University, Department of Gastroenterology, Xi’an, People’s Republic of China (GRID:grid.452438.c)
4 First Affiliated Hospital of Xi’an Jiaotong University, National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine and Surgical Engineering Research Center of Shaanxi Province, Xi’an, People’s Republic of China (GRID:grid.452438.c)
5 Xijing Hospital, Fourth Military Medical University, Department of Experimental Surgery, Xi’an, People’s Republic of China (GRID:grid.417295.c) (ISNI:0000 0004 1799 374X)
6 Tangdu Hospital, Fourth Military Medical University, Department of Pathology, Xi’an, People’s Republic of China (GRID:grid.460007.5) (ISNI:0000 0004 1791 6584)
7 Xi’an Jiaotong University, Frontier Institute of Science and Technology, and State Key Laboratory for Mechanical Behavior of Materials, Xi’an, China (GRID:grid.43169.39) (ISNI:0000 0001 0599 1243); Xi’an Jiaotong University, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an, People’s Republic of China (GRID:grid.43169.39) (ISNI:0000 0001 0599 1243)