Kawabata Atsuyuki, Egawa Satoru, Ogino Makoto, Yoshii Toshitaka
Department of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Astellas Pharma Inc. Drug Discovery Research, Tokyo, Japan.
Spine Surg Relat Res. 2024 Sep 9;9(2):218-225. doi: 10.22603/ssrr.2024-0147. eCollection 2025 Mar 27.
During spinal surgery, management of intraoperative bleeding and effective hemostasis are required to clearly visualize the surgical field and to safely perform procedures and positive postoperative outcomes. However, it is challenging to stop bleeding from the venous plexus around the dural sac due to the potential risk of neural tissue damage. We aimed to develop hemostatic sheets with appropriate characteristics for spinal surgery, such as softness, appropriate thickness, biodegradability, thrombin bioactivity, and minimal water-induced expansion.
Hemostatic sheets were made by dissolving bovine bone-derived gelatin in water and aerating it to form foam, followed by freeze-drying, crosslinking, and thrombin-soaking. Sheets A to H were produced with different gelatin concentrations, foam densities, and crosslinking times by additional heat treatment. The sheets were then soaked in thrombin solution for enhanced hemostasis. Material properties, such as density, tensile strength, biodegradability, and hemostatic capacity, were evaluated. Sheet efficacy was further assessed with liver bleeding and spinal venous plexus bleeding models in a miniature pig.
High-density gelatin sheets showed stable shape retention in wet conditions and robust tensile strength. Sheets with higher density and more crosslinking had prolonged persistence in the pepsin test and lower biodegradability in vivo. Sheet B, produced from a 4% gelatin solution with heating at 155°C for 4 h, showed the best balance of properties, such as no deformation cracks, rapid water absorption, minimal expansion, and faster degradation within 10 weeks, compared with TachoSil and other sheets. In hemostasis models, Sheet B outperformed Avitene and TachoSil, achieving higher success rates in spinal (four out of six sites) and liver bleeding (five out of five sites) models.
A thrombin-loaded hemostatic sheet produced from 4% gelatin solution with a short heating time for crosslinking demonstrated well-balanced material properties, such as shape retention, biodegradability, and wet expansion rate, which resulted in effective hemostasis in in vivo models. These advances may contribute to surgical hemostatic applications.
在脊柱手术中，术中出血的管理和有效的止血措施对于清晰观察手术视野、安全地进行手术操作以及实现良好的术后效果至关重要。然而，由于存在神经组织损伤的潜在风险，要止住硬脊膜囊周围静脉丛的出血具有挑战性。我们旨在开发具有适合脊柱手术的特性的止血片，如柔软性、合适的厚度、生物可降解性、凝血酶生物活性以及最小的水诱导膨胀。
通过将牛骨源明胶溶解于水中并通气形成泡沫，随后进行冷冻干燥、交联和凝血酶浸泡来制备止血片。通过额外的热处理，以不同的明胶浓度、泡沫密度和交联时间制备了A至H片。然后将这些片浸泡在凝血酶溶液中以增强止血效果。评估了材料特性，如密度、拉伸强度、生物可降解性和止血能力。在小型猪的肝出血和脊柱静脉丛出血模型中进一步评估了片的效果。
高密度明胶片在潮湿条件下显示出稳定的形状保持和强大的拉伸强度。密度更高且交联更多的片在胃蛋白酶试验中具有更长的持久性，并且在体内具有更低的生物可降解性。由4%明胶溶液在155°C加热4小时制成的B片显示出最佳的性能平衡，例如无变形裂缝、快速吸水、最小膨胀以及在10周内更快降解，与速即纱和其他片相比。在止血模型中，B片优于爱维治和速即纱，在脊柱出血模型（六个部位中的四个）和肝出血模型（五个部位中的五个）中获得了更高的成功率。
由4%明胶溶液经短时间加热交联制成的载凝血酶止血片表现出形状保持、生物可降解性和湿膨胀率等良好平衡的材料特性，这在体内模型中实现了有效的止血。这些进展可能有助于手术止血应用。
