可注射硫酸化纤维素纳米晶水凝胶中的细胞浸润及通过负载血管内皮生长因子实现高效血管生成
Cellular infiltration in an injectable sulfated cellulose nanocrystal hydrogel and efficient angiogenesis by VEGF loading.
作者信息
Min Kiyoon, Tae Giyoong
机构信息
School of Materials Science and Engineering, Gwangju Institute of Science and Technology, 123 Cheomdan-Gwagiro, Buk-Gu, Gwangju, 61005, Republic of Korea.
出版信息
Biomater Res. 2023 Apr 10;27(1):28. doi: 10.1186/s40824-023-00373-y.
BACKGROUND
Cellular infiltration and angiogenesis into implanted biomaterial scaffolds are crucial for successful host tissue integration and tissue regeneration. Cellulose nanocrystal (CNC) is a nano-sized cellulose derivative, which can form an injectable physical gel with salts. Sulfate groups of sulfated CNC (CNC-S) can act as a binding domain to various growth factors and cytokines with a heparin-binding domain for sustained release of them. Vascular endothelial growth factor (VEGF) can promote the proliferation of endothelial cells and angiogenesis. In this study, VEGF-loaded CNC-S hydrogel was evaluated as an injectable scaffold that can induce cellular infiltration and angiogenesis.
METHODS
CNC-S was hydrolyzed to get desulfated CNC (CNC-DS), which was used as a negative control group against CNC-S. Both CNC-S and CNC-DS hydrogels were prepared and compared in terms of biocompatibility and VEGF release. The hydrogels with or without VEGF loading were subcutaneously injected into mice to evaluate the biocompatibility, cellular infiltration, and angiogenesis induction of the hydrogels.
RESULTS
Both hydrogels possessed similar stability and shear-thinning behavior to be applicable as injectable hydrogels. However, CNC-S hydrogel showed sustained release (until 8 weeks) of VEGF whereas CNC-DS showed a very fast release of VEGF with a large burst. Subcutaneously injected CNC-S hydrogel showed much enhanced cellular infiltration as well as better biocompatibility with milder foreign body response than CNC-DS hydrogel. Furthermore, VEGF-loaded CNC-S hydrogel induced significant angiogenesis inside the hydrogel whereas VEGF-loaded CNC-DS did not.
CONCLUSION
CNC-S possesses good properties as a biomaterial including injectability, biocompatibility, and allowing cellular infiltration and sustained release of growth factors. VEGF-loaded CNC-S hydrogel exhibited efficient angiogenesis inside the hydrogel. The sulfate group of CNC-S was a key for good biocompatibility and the biological activities of VEGF-loaded CNC hydrogel.
背景
细胞浸润和血管生成进入植入的生物材料支架对于宿主组织的成功整合和组织再生至关重要。纤维素纳米晶体（CNC）是一种纳米尺寸的纤维素衍生物，它能与盐形成可注射的物理凝胶。硫酸化纤维素纳米晶体（CNC-S）的硫酸根可作为与各种生长因子和细胞因子结合的结构域，具有肝素结合结构域以实现它们的持续释放。血管内皮生长因子（VEGF）可促进内皮细胞增殖和血管生成。在本研究中，评估了负载VEGF的CNC-S水凝胶作为一种可诱导细胞浸润和血管生成的可注射支架。
方法
将CNC-S水解以获得去硫酸化的CNC（CNC-DS），其用作针对CNC-S的阴性对照组。制备了CNC-S和CNC-DS水凝胶，并在生物相容性和VEGF释放方面进行比较。将负载或未负载VEGF的水凝胶皮下注射到小鼠体内，以评估水凝胶的生物相容性、细胞浸润和血管生成诱导能力。
结果
两种水凝胶都具有相似的稳定性和剪切变稀行为，适用于可注射水凝胶。然而，CNC-S水凝胶显示出VEGF的持续释放（直至8周），而CNC-DS显示出VEGF的非常快速的释放且有很大的突释。皮下注射的CNC-S水凝胶显示出比CNC-DS水凝胶更强的细胞浸润以及更好的生物相容性和更轻微的异物反应。此外，负载VEGF的CNC-S水凝胶在水凝胶内部诱导了显著的血管生成，而负载VEGF的CNC-DS则没有。
结论
CNC-S作为生物材料具有良好的性能，包括可注射性、生物相容性以及允许细胞浸润和生长因子的持续释放。负载VEGF的CNC-S水凝胶在水凝胶内部表现出有效的血管生成。CNC-S的硫酸根是负载VEGF的CNC水凝胶具有良好生物相容性和生物学活性的关键。
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