Gold Nanoparticle-Functionalized Reverse Thermal Gel for Tissue Engineering Applications

Abstract

Utilizing polymers in cardiac tissue engineering holds promise for restoring function to the heart following myocardial infarction, which is associated with grave morbidity and mortality. To properly mimic native cardiac tissue, materials must not only support cardiac cell growth but also have inherent conductive properties. Here, we present an injectable reverse thermal gel (RTG)-based cardiac cell scaffold system that is both biocompatible and conductive. Following the synthesis of a highly functionalizable, biomimetic RTG backbone, gold nanoparticles (AuNPs) were chemically conjugated to the backbone to enhance the system’s conductivity. The resulting RTG-AuNP hydrogel supported targeted survival of neonatal rat ventricular myocytes (NRVMs) for up to 21 days when cocultured with cardiac fibroblasts, leading to an increase in connexin 43 (Cx43) relative to control cultures (NRVMs cultured on traditional gelatin-coated dishes and RTG hydrogel without AuNPs). This biomimetic and conductive RTG-AuNP hydrogel holds promise for future cardiac tissue engineering applications.

Advances in Nanomaterials for Injured Heart Repair

“…The main pathological mechanisms involved in the pathological process of ASCVD are oxidative stress, inflammation, and cell apoptosis, which contribute to the ventricular remodeling process after myocardium injury. In this section, the application of NMs treating ASCVD by acting on the noted mechanisms is discussed ( Ohnishi et al, 2007 ; Pagliari et al, 2012 ; Soumya et al, 2014 ; Lewis et al, 2015 ; Park et al, 2015 ; Wang et al, 2015 ; Koppara et al, 2016 ; Navaei et al, 2016 ; Somasuntharam et al, 2016 ; Vrijsen et al, 2016 ; Beldman et al, 2017 ; Chen et al, 2017 ; Gallet et al, 2017 ; Hao et al, 2017 ; Li et al, 2017 ; Rufaihah et al, 2017 ; Chen et al, 2018 ; Hosoyama et al, 2018 ; Wu et al, 2018 ; Zhu et al, 2018 ; Zhang et al, 2019a ; Zhang et al, 2019b ; Peña et al, 2019 ; Sun et al, 2019 ; Dong et al, 2020 ; Gao et al, 2020 ; Lai et al, 2020 ; Tashakori-Miyanroudi et al, 2020 ; Zhang et al, 2021 ) (summarized in Table 1 ).…”

“…In such studies, metal NMs or carbon NMs are incorporated into biological materials, such as hydrogels, to improve electrical conductivity and mechanical stiffness. When used for MI therapy by local injection or patch, this scheme increases the uniform expression of connexin 43 ( Navaei et al, 2016 ; Hosoyama et al, 2018 ; Peña et al, 2019 ), a cardiac specific marker, enhances the proliferation and expansion of cardiomyocytes ( Dong et al, 2020 ; Tashakori-Miyanroudi et al, 2020 ), promotes angiogenesis ( Hosoyama et al, 2018 ; Tashakori-Miyanroudi et al, 2020 ), and improves cell alignment and construction to repair contractile and conductive myocardial tissue irreversibly forfeited after MI.…”

Nanomaterials for Cardiac Tissue Engineering

“…Our group has recently investigated reverse thermal gels (RTGs) containing AuNPs for in vitro growth of NRVM cells [81]. RTGs are composed of poly(serinol hexamethylene urea)-co-PNIPAAm and have the property of being injectable due to a sol-gel transition temperature between 25 • C and 37 • C. The chemical incorporation of AuNPs into the RTG backbone decreased their electrical resistances (333.7 kΩ ± 50.5 for RTG only controls versus 140.1 kΩ ± 34.9 for RTG-AuNP gels).…”

Next Stage Approach to Tissue Engineering Skeletal Muscle

“…During tissue maturation, a more uniform electrical transmission of engineered tissues is achieved with electrically conductive materials. This can be improved by adding conductive materials to the scaffolds during fabrication, such as graphene oxide [ 63 ] or nanoparticles [ 64 ]. A further example are gold nanowires, mixed with a collagen-based bioink and electrically aligned during 3D printing to provide topographical cues to the cells.…”