Mizuno Yosuke, Taguchi Tetsushi
Graduate School of Science and Technology, University of Tsukuba 1-1-1 Tennodai Tsukuba Ibaraki 305-8577 Japan.
Polymers and Biomaterials Field, Research Center for Functional Materials, National Institute for Materials Science 1-1 Namiki Tsukuba Ibaraki 305-0044 Japan
RSC Adv. 2020 Jun 30;10(42):24800-24807. doi: 10.1039/d0ra03593a. eCollection 2020 Jun 29.
In tissue engineering and regenerative medicine, the formation of vascular beds is an effective method to supply oxygen and nutrients to implanted cells or tissues to improve their survival and promote normal cellular functions. Various types of angiogenic materials have been developed by incorporating growth factors, such as vascular endothelial growth factor, in biocompatible materials. However, these exogenous growth factors suffer from instability and inactivation under physiological conditions. In this study, we designed a novel angiogenic electrospun fiber sheet (C16-FS) composed of Alaska pollock-derived gelatin (ApGltn) modified with hexadecyl (C16) groups to induce localized and sustained angiogenesis without growth factors. C16-FS was thermally crosslinked to enhance its stability. We demonstrated that C16-FS swells in phosphate-buffered saline for over 24 h and resists degradation. Laser doppler perfusion imaging showed that C16-FS induced increased blood perfusion when implanted subcutaneously in rats compared with unmodified ApGltn-fiber sheets (Org-FS) and the sham control. Furthermore, angiogenesis was sustained for up to 7 days following implantation. Immunohistochemical studies revealed elevated nuclear factor-κB and CD31 levels around the C16-FS implantation site compared with the Org-FS implantation site and the control incision site. These results demonstrate that C16-FS is a promising angiogenic material to promote the formation of vascular beds for cell and tissue transplantation without the need for growth factors.
在组织工程和再生医学中，血管床的形成是一种向植入的细胞或组织供应氧气和营养物质以提高其存活率并促进正常细胞功能的有效方法。通过在生物相容性材料中掺入生长因子，如血管内皮生长因子，已经开发出了各种类型的促血管生成材料。然而，这些外源性生长因子在生理条件下会出现不稳定和失活的情况。在本研究中，我们设计了一种新型的促血管生成电纺纤维片（C16-FS），它由用十六烷基（C16）基团修饰的狭鳕鱼明胶（ApGltn）组成，能够在无需生长因子的情况下诱导局部和持续的血管生成。C16-FS经过热交联以增强其稳定性。我们证明C16-FS在磷酸盐缓冲盐水中会膨胀超过24小时并且抗降解。激光多普勒血流成像显示，与未修饰的ApGltn纤维片（Org-FS）和假手术对照组相比，C16-FS皮下植入大鼠后可诱导血流灌注增加。此外，植入后血管生成可持续长达7天。免疫组织化学研究显示，与Org-FS植入部位和对照切口部位相比，C16-FS植入部位周围的核因子-κB和CD31水平升高。这些结果表明，C16-FS是一种有前景的促血管生成材料，可在无需生长因子的情况下促进用于细胞和组织移植的血管床形成。
