Department of Engineering Mechanics, Zhejiang University, Hangzhou, 310027, China.
Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province, Zhejiang University, Hangzhou, 310027, China.
Mil Med Res. 2023 Mar 23;10(1):15. doi: 10.1186/s40779-023-00451-1.
Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging.
This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery.
ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m for the heart, (607.6 ± 30.0) J/m for the intestine, (473.7 ± 37.0) J/m for the liver, (186.1 ± 13.3) J/m for muscle, and (579.3 ± 32.3) J/m for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface.
ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.
受损组织的重建需要表面止血和组织桥接。由于物理创伤或手术治疗而受损的组织可能具有任意的表面形貌，因此组织桥接具有挑战性。
本研究提出了一种由壳聚糖、丙烯酸、1-乙基-3-(3-二甲基氨基丙基)碳二亚胺（EDC）和 N-羟基琥珀酰亚胺（NHS）制成的胶态冷冻颗粒形式的组织粘合剂（ACPs）。通过对包括猪心、肠、肝、肌肉和胃在内的一系列组织进行 180 度剥离试验来检查粘附性能。通过人正常肝细胞（LO2）和人肠上皮细胞（Caco-2）的细胞增殖来评估 ACPs 的细胞毒性。通过背部皮下大鼠模型检查炎症程度和生物降解性。使用猪心、肝和肾作为离体模型评估 ACPs 桥接不规则组织缺陷的能力。此外，建立了大鼠肝破裂和兔肠吻合术模型，以验证其在临床手术中的有效性、生物相容性和适用性。
ACPs 适用于受限和不规则的组织缺陷，例如实质器官的深人字形槽和海绵状器官的环形部分。ACPs 在组织之间形成了坚固的粘附力[（670.9±50.1）J/m 用于心脏，（607.6±30.0）J/m 用于肠，（473.7±37.0）J/m 用于肝，（186.1±13.3）J/m 用于肌肉，（579.3±32.3）J/m 用于胃]。ACPs 在体外研究中表现出相当好的细胞相容性，细胞活力高，第 3 天达到[（98.8±1.2）%用于 LO2 和（98.3±1.6）%用于 Caco-2]。在大鼠肝破裂中具有可比的炎症修复作用（与缝合闭合相比，P=0.58），在兔肠吻合术（与缝合吻合相比，P=0.40）中也具有相同的作用。此外，基于 ACPs 的肠吻合术（少于 30 秒）明显快于传统缝合过程（超过 10 分钟）。当 ACPs 在手术后降解时，组织在粘附界面处愈合。
ACPs 有望成为临床手术和战场救援的理想粘合剂，具有快速桥接不规则组织缺陷的能力。
