Department of Bioengineering, University of Pennsylvania, 210 33rd Street, Philadelphia, PA, 19104, USA.
Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, Yale Translational Research Imaging Center, DANA-3, P.O. Box 208017, New Haven, CT, 06520-8017, USA.
Adv Healthc Mater. 2020 Jul;9(14):e2000294. doi: 10.1002/adhm.202000294. Epub 2020 Jun 15.
Injectable hydrogels are being widely explored for treatment after myocardial infarction (MI) through mechanical bulking or the delivery of therapeutics. Despite this interest, there have been few approaches to image hydrogels upon injection to identify their location, volume, and pattern of delivery, features that are important to understand toward clinical translation. Using a hyaluronic acid (HA) hydrogel as an example, the aim of this study is to introduce radiopacity to hydrogels by encapsulating a clinically used contrast agent (Omnipaque Iohexol, GE Healthcare) for imaging upon placement in the myocardium. Specifically, iohexol is encapsulated into shear-thinning and self-healing hydrogels formed through the mixing of HA-hydrazide and HA-aldehyde. Upon examination of a range of iohexol concentrations, a concentration of 100 mg mL iohexol is deemed optimal based on the greatest contrast, while maintaining hydrogel mechanical properties and acceptable injection forces. In an acute porcine model of MI, hybrid single-photon emission computed tomography/computed tomography (SPECT/CT) perfusion imaging is performed immediately and 3-4 days after hydrogel delivery to assess radiopacity and verify the hydrogel location within the perfusion defect. Hybrid SPECT/CT imaging demonstrates excellent radiopacity of the hydrogel within the perfusion defect immediately after intramyocardial hydrogel injection, demonstrating the feasibility of this method for short-term noninvasive hydrogel monitoring.
可注射水凝胶通过机械膨胀或输送治疗剂,正在被广泛探索用于心肌梗死(MI)后的治疗。尽管人们对此很感兴趣,但很少有方法可以在注射后对水凝胶进行成像,以确定其位置、体积和输送模式,这些特征对于理解向临床转化很重要。本研究以透明质酸(HA)水凝胶为例,旨在通过包封一种临床使用的造影剂(GE Healthcare 的欧乃派克碘海醇)来为水凝胶赋予放射学显影性,从而在心肌内注射后进行成像。具体来说,碘海醇被包封在通过混合 HA-酰肼和 HA-醛形成的剪切稀化和自修复水凝胶中。在考察了一系列碘海醇浓度后,根据最大对比度,同时保持水凝胶的机械性能和可接受的注射力,将 100mg/mL 的碘海醇浓度确定为最佳浓度。在 MI 的急性猪模型中,在心肌内注射水凝胶后立即和 3-4 天进行混合单光子发射计算机断层扫描/计算机断层扫描(SPECT/CT)灌注成像,以评估放射学显影性并验证水凝胶在灌注缺陷内的位置。混合 SPECT/CT 成像立即在心肌内注射水凝胶后在灌注缺陷内显示出色的水凝胶放射学显影性,证明了这种方法用于短期非侵入性水凝胶监测的可行性。