Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels

Abstract

Drug-loaded injectable hydrogels have been proven to possess huge potential for applications in tissue engineering. However, increasing the drug loading capacity and regulating the release system to adapt to the microenvironment after myocardial infarction face a huge challenge. In this research, an ROS-sensitive injectable hydrogel strengthened by self-nanodrugs was constructed. A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition. Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly. The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels. The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro. Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.

A Reactive Oxygen Species Scavenging and O2 Generating Injectable Hydrogel for Myocardial Infarction Treatment In vivo

“…The anti‐oxidation property of HBPAK was first assessed by DPPH assay. [ 6 ] The dark purple color of DPPH/HBPAK solution faded very apparently after 125 min compared to the DPPH ethanol solution (Figure 2C). Quantitative analysis by UV–Vis showed that along with time prolongation the absorbance of DPPH in the DPPH/HBPAK solution decreased monotonously (Figure S2A, Supporting Information), revealing the steady clearance of DPPH (Figure 2D).…”

“…The use of stem cells faces several limitations such as low cell retention, time‐consuming of cell preparation, and potential allogeneic immune response, etc. [ 4 ] By contrast, the use of regenerative biomaterials can avoid these limitations, while the therapeutic performance can be well manipulated by using patches, [ 5 ] hydrogels, [ 6 ] scaffolds, [ 7 ] or particles. [ 8 ] In particular, the injectable hydrogels have the advantages of easy surgical operation and direct injection into the infarcted area, [ 9 ] leading to the most effective therapeutic effect on MI and restoration of the myocardial functions.…”

Recent Advances in Injectable Hydrogels for Controlled and Local Drug Delivery

“…When injected into heart muscle, this hydrogel was found to improve cardiac functions by decreasing inflammation. [83] Click chemistry is another alternative to creating injectable hydrogels via chemical crosslinking. This approach provides short reaction times with high-yield chemoselectivity and can be performed under mild reaction conditions.…”

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

“…In addition to ROS-triggered drug release, polymers with ROS-responsive bonds in their backbones or side chains are capable of consuming the excessive ROS produced by the MI. This reduces injury to the cardiac tissue, and has the potential for preventing and treating cardiovascular disease [133][134][135]. Yao et al reported a biodegradable elastomeric polyurethanes (PUTK) with ROS-responsive properties, which they made fibrous patches from.…”