He Jiahui, Zhang Zixi, Yang Yutong, Ren Fenggang, Li Jipeng, Zhu Shaojun, Ma Feng, Wu Rongqian, Lv Yi, He Gang, Guo Baolin, Chu Dake
Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Frontier Institute of Science and Technology, and State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China.
Nanomicro Lett. 2021 Feb 27;13(1):80. doi: 10.1007/s40820-020-00585-0.
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.
内镜黏膜切除术（EMR）和内镜黏膜下剥离术（ESD）是治疗胃肠道肿瘤的成熟方法，但EMR/ESD术后的并发症，包括出血和穿孔，会导致额外的治疗 morbidity，甚至危及患者生命。因此，设计生物材料来治疗内镜治疗后的胃出血和伤口愈合是非常必要的，并且仍然是一个挑战。在此，开发了一系列基于丙烯酰基-6-氨基己酸（AA）和AA-g-N-羟基琥珀酰亚胺（AA-NHS）的可注射pH响应性自愈合粘附水凝胶，并在猪胃出血/伤口模型中进一步证明了它们作为内镜可喷涂生物粘附材料有效止血和促进伤口愈合过程的巨大潜力。这些水凝胶表现出合适的凝胶化时间、自主高效的自愈合能力、止血性能和良好的生物相容性。随着作为微交联剂的AA-NHS的引入，水凝胶的粘附强度增强。猪胃出血体内模型表明，这些水凝胶通过停止急性动脉出血和预防延迟出血表现出良好的止血性能。胃伤口模型表明，这些水凝胶显示出优异的治疗效果，I型胶原沉积、α-SMA表达和血管形成显著增强，伤口愈合加快。这些可注射自愈合粘附水凝胶在内镜治疗后治疗胃伤口方面具有巨大潜力。
