Renmin Hospital of Wuhan University, 430060 Wuhan, China.
Wuhan University School of Basic Medical Science, 430060 Wuhan, China.
Int J Biol Macromol. 2023 Jul 31;244:125139. doi: 10.1016/j.ijbiomac.2023.125139. Epub 2023 Jun 1.
Heart failure is a critical and ultimate phase of cardiovascular ailment that leads to a considerable incidence of disability and mortality. Among various factors contributing to heart failure, myocardial infarction is one of the most frequent and significant causes, which is still difficult to manage effectively. An innovative therapeutic strategy, namely a 3D bio-printed cardiac patch, has recently emerged as a promising approach to substitute damaged cardiomyocytes in a localized infarct region. Nevertheless, the efficacy of this treatment primarily relies on the long-term viability of the transplanted cells. In this study, we aimed to construct acoustically sensitive nano oxygen carriers to improve cell survival inside the bio-3D printed patch. In this study, we initially created nanodroplets capable of phase transition triggered by ultrasound and integrated them into GelMA (Gelatin Methacryloyl) hydrogels, which were then employed for 3D bioprinting. After adding nanodroplets and ultrasonic irradiation, numerous pores appeared inside the hydrogel with improved permeability. We further encapsulated hemoglobin into nanodroplets (ND-Hb) to construct oxygen carriers. Results of in vitro experiments showed the highest cell survival within the patch of ND-Hb irradiated by the low-intensity pulsed ultrasound (LIPUS) group. The genomic analysis discovered that the increased survival of seeded cells within the patch might be related to the protection of mitochondrial function owing to the improved hypoxic state. Eventually, in vivo studies revealed that the LIPUS+ND-Hb group had improved cardiac function and increased revascularization after myocardial infarction. To summarize, our study successfully improved the permeability of the hydrogel in a non-invasive and efficient manner, facilitating the exchange of substances in the cardiac patch. Moreover, ultrasound-controlled oxygen release augmented the viability of the transplanted cells and expedited the repair of infarcted tissues.
心力衰竭是心血管疾病的一个关键和终末期阶段，导致相当高的残疾和死亡率。在导致心力衰竭的各种因素中，心肌梗死是最常见和最重要的原因之一，仍然难以有效治疗。一种创新的治疗策略，即 3D 生物打印心脏贴片，最近已成为替代局部梗死区域受损心肌细胞的有前途的方法。然而，这种治疗的疗效主要依赖于移植细胞的长期存活能力。在本研究中，我们旨在构建对声音敏感的纳米氧载体，以提高生物 3D 打印贴片内细胞的存活率。在本研究中，我们首先创建了能够通过超声触发相转变的纳米液滴，并将其整合到 GelMA（明胶甲基丙烯酰）水凝胶中，然后用于 3D 生物打印。添加纳米液滴并进行超声辐射后，水凝胶内部出现了许多渗透性得到改善的孔。我们进一步将血红蛋白封装到纳米液滴中（ND-Hb）以构建氧载体。体外实验结果表明，在低强度脉冲超声（LIPUS）照射下的 ND-Hb 贴片内的细胞存活率最高。基因组分析发现，贴片内接种细胞存活率的增加可能与改善的低氧状态下保护线粒体功能有关。最终，体内研究表明，LIPUS+ND-Hb 组在心肌梗死后具有改善的心脏功能和增加的再血管化。总之，我们的研究成功地以非侵入性和高效的方式改善了水凝胶的渗透性，促进了心脏贴片内物质的交换。此外，超声控制的氧释放增强了移植细胞的活力，并加速了梗死组织的修复。
