Faculty of Chemistry, Materials, and Bioengineering, Kansai University, 3-3-35 Yamate, Suita, Osaka 564-8680, Japan.
Organization for Research and Development of Innovative Science and Technology (ORDIST), Kansai University, 3-3-35 Yamate, Suita, Osaka 564-8680, Japan.
Acta Biomater. 2021 Nov;135:318-330. doi: 10.1016/j.actbio.2021.08.033. Epub 2021 Aug 28.
Injectable polymers (IPs) exhibiting in situ hydrogel formation have attracted attention as vascular embolization and postoperative adhesion prevention materials. While utilizing hydrogels for such purposes, it is essential to ensure that they have appropriate and controllable tissue adhesion property, as it is crucial for them to not detach from their deposited location in the blood vessel or abdominal cavity. Additionally, it is important to maintain gel state in vivo for the desired period at such locations, where large amounts of body fluid exist. We had previously reported on a biodegradable IP system exhibiting temperature-responsive gelation and subsequent covalent cross-link formation. We had utilized triblock copolymers of aliphatic polyester and poly(ethylene glycol) (tri-PCGs) and its derivative containing acrylate group at the termini (tri-PCG-Acryl), exhibiting a longer and more controllable duration time of the gel state. In this study, the introduction of aldehyde groups by the addition of aldehyde-modified Pluronic (PL-CHO) was performed for conferring controllable and appropriate tissue adhesive properties on these IP systems. The IP systems containing PL-CHO, which were not covalently incorporated into the hydrogel network, exhibited tissue adhesive properties through Schiff base formation. The adhesion strength could be controlled by the amount of PL-CHO added. The IP system showed good vascular embolization performance and pressure resistance in the blood vessels. The IP hydrogel remained at the administration site in the abdominal space for 2 days and displayed effective adhesion prevention performance. STATEMENT OF SIGNIFICANCE: Injectable polymers (IPs), which exhibit in situ hydrogel formation, are expected to be utilized as vascular embolization and postoperative adhesion prevention materials. The tissue adhesion properties of hydrogels are important for such applications. We succeeded in conferring tissue adhesion properties onto a previously reported IP system by mixing it with Pluronic modified with aldehyde groups (PL-CHO). The aldehyde groups allowed for the formation of Schiff bases at the tissue surfaces. The tissue adhesion property could be conveniently controlled by altering the amount of PL-CHO. We revealed that the in vitro embolization properties of IPs in blood vessels could be substantially improved by mixing with PL-CHO. The IP system containing PL-CHO also exhibited good in vivo performance for postoperative adhesion prevention.
可注射聚合物（IPs）具有原位水凝胶形成的特性，已作为血管栓塞和术后防粘连材料引起了人们的关注。在将水凝胶用于这些目的时，确保其具有适当且可控制的组织粘附特性非常重要，因为它们在血管或腹腔内的沉积位置不会脱落至关重要。此外，在存在大量体液的这些位置，在体内保持凝胶状态所需的时间也很重要。我们之前曾报道过一种具有温度响应凝胶化和随后的共价交联形成的可生物降解的 IP 系统。我们曾利用脂肪族聚酯和聚（乙二醇）的三嵌段共聚物（三 PCG）及其末端含有丙烯酸酯基团的衍生物（三 PCG-Acryl），其凝胶状态的持续时间更长且更可控。在这项研究中，通过添加醛基改性的 Pluronic（PL-CHO），引入了醛基，以赋予这些 IP 系统可控制和适当的组织粘合特性。包含 PL-CHO 的 IP 系统未共价掺入水凝胶网络中，通过席夫碱形成表现出组织粘合特性。通过添加 PL-CHO 的量可以控制粘附强度。该 IP 系统在血管中显示出良好的血管栓塞性能和耐压性。IP 水凝胶在腹腔给药部位保留了 2 天，并显示出有效的防粘连性能。 意义声明：可注射聚合物（IPs）具有原位水凝胶形成的特性，有望作为血管栓塞和术后防粘连材料使用。水凝胶的组织粘附特性对于这些应用很重要。我们通过将其与用醛基改性的 Pluronic（PL-CHO）混合，成功地赋予了之前报道的 IP 系统组织粘附特性。醛基允许在组织表面形成席夫碱。通过改变 PL-CHO 的量，可以方便地控制组织粘附特性。我们揭示了通过与 PL-CHO 混合，可大大改善 IP 在血管中的体外栓塞特性。含有 PL-CHO 的 IP 系统也表现出良好的术后防粘连体内性能。
