Conductive nanocomposite hydrogel and mesenchymal stem cells for the treatment of myocardial infarction and non-invasive monitoring via PET/CT

Abstract

Background Injectable hydrogels have great promise in the treatment of myocardial infarction (MI); however, the lack of electromechanical coupling of the hydrogel to the host myocardial tissue and the inability to monitor the implantation may compromise a successful treatment. The introduction of conductive biomaterials and mesenchymal stem cells (MSCs) may solve the problem of electromechanical coupling and they have been used to treat MI. In this study, we developed an injectable conductive nanocomposite hydrogel (GNR@SN/Gel) fabricated by gold nanorods (GNRs), synthetic silicate nanoplatelets (SNs), and poly(lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA). The hydrogel was used to encapsulate MSCs and 68Ga3+ cations, and was then injected into the myocardium of MI rats to monitor the initial hydrogel placement and to study the therapeutic effect via 18F-FDG myocardial PET imaging. Results Our data showed that SNs can act as a sterically stabilized protective shield for GNRs, and that mixing SNs with GNRs yields uniformly dispersed and stabilized GNR dispersions (GNR@SN) that meet the requirements of conductive nanofillers. We successfully constructed a thermosensitive conductive nanocomposite hydrogel by crosslinking GNR@SN with PLGA2000-PEG3400-PLGA2000, where SNs support the proliferation of MSCs. The cation-exchange capability of SNs was used to adsorb 68Ga3+ to locate the implanted hydrogel in myocardium via PET/CT. The combination of MSCs and the conductive hydrogel had a protective effect on both myocardial viability and cardiac function in MI rats compared with controls, as revealed by 18F-FDG myocardial PET imaging in early and late stages and ultrasound; this was further validated by histopathological investigations. Conclusions The combination of MSCs and the GNR@SN/Gel conductive nanocomposite hydrogel offers a promising strategy for MI treatment. Graphical Abstract

Berberin sustained-release nanoparticles were enriched in infarcted rat myocardium and resolved inflammation

“…Cardiac structures, including electrical signal transmission networks, vascular networks, and cardiomyocytes [ 40 ], were assessed on day 28 by immunofluorescence analysis.…”

Biomaterials‐Based Cell Therapy for Myocardial Tissue Regeneration

“…In addition, PEG is often combined with other compounds such as PCL and PLGA to form block polymers to prepare bioactive materials. [63,142] Zhu et al [143] prepared thermosensitive hydrogels based on gold nanorods (GNR), synthetic silicate nanosheets (SN), and PLGA-PEG-PLGA to treat MI in rats by loading MSCs. Among them, SN is a cross-linking agent, and GNR is used to adsorb biologically active substances to adhere to cells.…”

Insight into Heart-Tailored Architectures of Hydrogel to Restore Cardiac Functions after Myocardial Infarction

“…Implementing a radioactive tracer (1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) chelated with radioactive isotope 111 In) in pH-and temperature-responsive supramolecular PEG hydrogel allows for in vivo radioactive detection. 79,80 3.3.3. Stiffness.…”

“…Similarly, to increase tissue adhesiveness, a UPy-functionalized recombinant peptide based on human collagen type 1 is added to the hydrogel (UPy-PEG-RCPhC1) and enriched with repeating amino acid sequences based on the integrin-binding peptide, RGD. Implementing a radioactive tracer (1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) chelated with radioactive isotope In) in pH- and temperature-responsive supramolecular PEG hydrogel allows for in vivo radioactive detection. , …”