Center for Convergence Bioceramic Materials, Convergence R&D Division, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk, 28160, Republic of Korea.
School of Materials Science and Engineering, Gwangju Institute of Science and Technology, 123 Cheomdan-gwagiro, Buk-gu, Gwangju, 61005, Republic of Korea.
Sci Rep. 2017 Oct 30;7(1):14351. doi: 10.1038/s41598-017-14040-5.
Growth factors have great therapeutic potential for various disease therapy and tissue engineering applications. However, their clinical efficacy is hampered by low bioavailability, rapid degradation in vivo and non-specific biodistribution. Nanoparticle based delivery systems are being evaluated to overcome these limitations. Herein, we have developed a thermosensitive heparin nanosponge (Hep-NS) by a one step photopolymerization reaction between diacrylated pluronic and thiolated heparin molecules. The amount of heparin in Hep-NS was precisely controlled by varying the heparin amount in the reaction feed. Hep-NS with varying amounts of heparin showed similar size and shape properties, though surface charge decreased with an increase in the amount of heparin conjugation. The anticoagulant activity of the Hep-NS decreased by 65% compared to free heparin, however the Hep-NS retained their growth factor binding ability. Four different growth factors, bFGF, VEGF, BMP-2, and HGF were successfully encapsulated into Hep-NS. In vitro studies showed sustained release of all the growth factors for almost 60 days and the rate of release was directly dependent on the amount of heparin in Hep-NS. The released growth factors retained their bioactivity as assessed by a cell proliferation assay. This heparin nanosponge is therefore a promising nanocarrier for the loading and controlled release of growth factors.
生长因子在各种疾病治疗和组织工程应用中具有巨大的治疗潜力。然而,它们的临床疗效受到生物利用度低、体内快速降解和非特异性生物分布的限制。基于纳米粒子的递药系统正在被评估以克服这些限制。在这里,我们通过二丙烯酰化的 pluronic 和巯基化肝素分子之间的一步光聚合反应开发了一种热敏性肝素纳米海绵(Hep-NS)。通过改变反应进料中的肝素量,可以精确控制 Hep-NS 中的肝素量。具有不同肝素量的 Hep-NS 具有相似的大小和形状特性,尽管表面电荷随着肝素结合量的增加而降低。与游离肝素相比,Hep-NS 的抗凝活性降低了 65%,但仍保留了其生长因子结合能力。四种不同的生长因子,bFGF、VEGF、BMP-2 和 HGF 成功地被包裹到 Hep-NS 中。体外研究表明,所有生长因子的释放几乎持续 60 天,释放速率直接取决于 Hep-NS 中的肝素量。通过细胞增殖测定评估,释放的生长因子保留了其生物活性。因此,肝素纳米海绵是生长因子负载和控制释放的有前途的纳米载体。
J Control Release. 2007-2-12
J Biomater Sci Polym Ed. 2012-5-11
Mater Sci Eng C Mater Biol Appl. 2018-1-1
Front Bioeng Biotechnol. 2022-5-12
Curr Osteoporos Rep. 2022-2
Front Cardiovasc Med. 2021-9-28
Bioengineering (Basel). 2021-9-10
Blood Coagul Fibrinolysis. 2013-10
J Control Release. 2011-8-16
J Control Release. 2011-7-2
Chem Commun (Camb). 2011-2-18
Int J Pharm. 2010-10-1