Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
State Key Laboratory for Mechanical Behavior of Materials, and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Acta Biomater. 2022 Oct 15;152:157-170. doi: 10.1016/j.actbio.2022.09.006. Epub 2022 Sep 12.
Nephron-sparing surgery is a well-established treatment in patients with T1a renal cell carcinoma; however, the complex suturing process prolongs warm ischaemia time, affects the preservation of normal renal parenchymal function, and causes avoidable postoperative tissue adhesion complications, including chronic abdominal pain, intestinal obstruction, and female infertility. Hence, the design of multifunctional biomaterials with haemostasis, postoperative wound management, and postoperative tissue adhesion prevention properties for nephron-sparing surgeries is urgently needed. In this study, a series of injectable adhesive multifunctional biocompatible hydrogels were designed based on the free-radical polymerisation of monomers acryloyl-6-aminocaproic acid (AA) and N-acryloyl 2-glycine (NAG), and the ionic coordination between Ca and the abundant carboxyl groups in AA and NAG. AA/NAG/Ca (AA, NAG, and Ca refer to acryloyl-6-aminocaproic acid, N-acryloyl 2-glycine and calcium chloride, respectively) hydrogel exhibited good mechanical properties, swelling and adhesion properties, flexibility, in vitro blood-clotting ability, and cytocompatibility. In vivo experiments on liver injury models and rat/rabbit nephron-sparing surgery models elucidated that the AA/NAG/Ca hydrogel had haemostasis performance and wound healing properties that led to short bleeding time, reduced bleeding volume, and well-organised nephron structures. An abdomen-caecum adhesion model indicated that the AA/NAG/Ca hydrogel showed excellent anti-adhesion properties. In summary, this multifunctional hydrogel exhibited potential for improving haemostasis and wound management in nephron-sparing surgeries, showing potential for clinical application. STATEMENT OF SIGNIFICANCE: Extended warm ischemia time during nephron sparing surgery negatively affected postoperative renal function due to the need for hemostasis at the wound with abundant blood supply, and postoperative wound healing and additional adhesions caused by the surgical procedure deserve attention. Based on the efficient and stable adhesion properties of hydrogels and the ability to promote wound healing. Herein, a series of adhesive self-healing biocompatible hydrogels were prepared based on free-radical polymerization of acryloyl-6-aminocaproic acid (AA) and N-acryloyl 2-glycine (NAG) and the ionic coordination between Ca with the abundant carboxyl groups in AA and NAG. AA/NAG/Ca hydrogel showed hemostasis property in nephron sparing surgery model, promote kidney wound healing, and could perform anti-postoperative adhesion efficacy in an abdomen-caecum adhesion model.
肾部分切除术是 T1a 肾细胞癌患者的一种成熟治疗方法；然而，复杂的缝合过程会延长热缺血时间，影响正常肾实质功能的保存，并导致可避免的术后组织粘连并发症，包括慢性腹痛、肠梗阻和女性不孕。因此，迫切需要设计具有止血、术后伤口管理和预防术后组织粘连特性的多功能生物材料用于肾部分切除术。在这项研究中，设计了一系列基于单体丙烯酰基-6-氨基己酸（AA）和 N-丙烯酰基 2-甘氨酸（NAG）的自由基聚合以及 Ca 与 AA 和 NAG 中丰富羧基之间的离子配位的可注射性胶粘剂多功能生物相容性水凝胶。AA/NAG/Ca（AA、NAG 和 Ca 分别代表丙烯酰基-6-氨基己酸、N-丙烯酰基 2-甘氨酸和氯化钙）水凝胶表现出良好的机械性能、溶胀和粘附性能、柔韧性、体外凝血能力和细胞相容性。肝损伤模型和大鼠/兔肾部分切除术模型的体内实验表明，AA/NAG/Ca 水凝胶具有止血性能和伤口愈合性能，可缩短出血时间、减少出血量，并使肾单位结构良好。腹部盲肠粘连模型表明，AA/NAG/Ca 水凝胶具有优异的防粘连性能。总之，这种多功能水凝胶在肾部分切除术中具有改善止血和伤口管理的潜力，显示出临床应用的潜力。
肾部分切除术期间延长的热缺血时间会因需要在富含血液供应的伤口处止血而对术后肾功能产生负面影响，并且手术过程引起的术后伤口愈合和额外粘连值得关注。基于水凝胶的高效和稳定的粘附特性以及促进伤口愈合的能力。在此，我们基于丙烯酰基-6-氨基己酸（AA）和 N-丙烯酰基 2-甘氨酸（NAG）的自由基聚合以及 Ca 与 AA 和 NAG 中丰富羧基之间的离子配位，制备了一系列粘附自修复生物相容性水凝胶。AA/NAG/Ca 水凝胶在肾部分切除术模型中表现出止血特性，促进肾脏伤口愈合，并在腹部盲肠粘连模型中表现出抗术后粘连作用。
