1 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
2 Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Ireland.
J Biomater Appl. 2018 Nov;33(5):681-692. doi: 10.1177/0885328218805878. Epub 2018 Oct 25.
Injectable hydrogels that aim to mechanically stabilise the weakened left ventricle wall to restore cardiac function or to deliver stem cells in cardiac regenerative therapy have shown promising data. However, the clinical translation of hydrogel-based therapies has been limited due to difficulties injecting them through catheters. We have engineered a novel catheter, Advanced Materials Catheter (AMCath), that overcomes translational hurdles associated with delivering fast-gelling covalently cross-linked hyaluronic acid hydrogels to the myocardium. We developed an experimental technique to measure the force required to inject such hydrogels and determined the mechanical/viscoelastic properties of the resulting hydrogels. The preliminary in vivo feasibility of delivering fast-gelling hydrogels through AMCath was demonstrated by accessing the porcine left ventricle and showing that the hydrogel was retained in the myocardium post-injection (three 200 μL injections delivered, 192, 204 and 183 μL measured). However, the mechanical properties of the hydrogels were reduced by passage through AMCath (≤20.62% reduction). We have also shown AMCath can be used to deliver cardiopoietic adipose-derived stem cell-loaded hydrogels without compromising the viability (80% viability) of the cells in vitro. Therefore, we show that hydrogel/catheter compatibility issues can be overcome as we have demonstrated the minimally invasive delivery of a fast-gelling covalently cross-linked hydrogel to the beating myocardium.
旨在通过机械稳定弱化的左心室壁以恢复心脏功能或在心脏再生治疗中递送干细胞的可注射水凝胶已经显示出了有前景的数据。然而,由于通过导管注射水凝胶存在困难,基于水凝胶的疗法的临床转化受到了限制。我们已经设计了一种新型导管,即高级材料导管(AMCath),它克服了将快速凝胶化的共价交联透明质酸水凝胶递送到心肌所涉及的转化障碍。我们开发了一种实验技术来测量注射这种水凝胶所需的力,并确定了所得水凝胶的机械/粘弹性特性。通过进入猪的左心室并显示在注射后水凝胶保留在心肌中(注射了三个 200μL,测量到的为 192、204 和 183μL),初步证明了通过 AMCath 递送快速凝胶化水凝胶的体内可行性。然而,水凝胶通过 AMCath 传递后其机械性能降低(≤20.62% 的降低)。我们还表明,AMCath 可用于递送载有心脏形成脂肪来源干细胞的水凝胶,而不会损害细胞的体外活力(活力为 80%)。因此,我们表明可以克服水凝胶/导管相容性问题,因为我们已经证明了可以将快速凝胶化的共价交联水凝胶微创递送到跳动的心肌中。