Chinese herb-crosslinked hydrogel bearing rBMSCs-laden polyzwitterion microgels: Self-adaptive manipulation of micromilieu and stemness maintenance for restoring infarcted myocardium. (December 2021)

• Record Type: Journal Article
• Authors: Liu, Yang; Zhang, Xiaoping; Wu, Tengling; Liu, Bo; Yang, Jianhai; Liu, Wenguang
• Is Part Of: Nano today. Volume 41(2021)
• Publication Date: 2021-12
• Subjects: Injectable hydrogel -- Polyzwitterionic microgels -- Stemness -- Microenvironment -- Myocardial infarction; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2021.101306
• Languages: English
• ISSNs: 1748-0132

Abstract

Highlights: Polyzwitterionic microgels is prepared in a home-made microfluidic system. rBMSCs in microgels can maintain stemness and shows increased paracrine effect. Chinese herb-crosslinked hydrogel bearing rBMSCs-laden polyzwitterion microgels is fabricated. Puerarin-crosslinked hydrogel bearing rBMSCs@microgels favorably modulates the micromilieu. HA-Try-PUE@rBMSCs@microgels facilitate efficient restoration of cardiac function. Graphical Abstract: ga1 Abstract: Injectable hydrogels and stem cells have been increasingly applied to treat myocardial infarction (MI). However, the harsh microenvironment adversely affects the survival of implanted stem cells and ultimate therapeutic outcomes. Herein, we design and prepare rat bone marrow mesenchymal stem cells (rBMSCs)-embedded polyzwitterionic microgels (rBMSCs@microgels) via in situ Michael addition reaction between multivinyl carboxybetaine macromonomer and thiol-ended polyethylene glycol mixed with rBMSCs in a microfluidic system. The rBMSCs@microgels are then loaded into a tyramine-modified hyaluronic acid (HA-Tyr), into which Chinese herb puerarin (PUE) and horseradish peroxidase (HRP)/H2 O2 are added to catalyze inter-phenol crosslinks to form an injectable HA-Tyr-PUE hydrogel encapsulating rBMSCs@microgels (HA-Tyr-PUE@rBMSCs@microgels). This HA-Tyr-PUE@rBMSCs@microgels is injected into the infarct region of rats, where HA-Tyr-PUE hydrogel serves to favorably modulate the microenvironment by scavenging active oxygen and releasing oxygen, and rBMSCs remain stemness in highly hydrophilic microgels and exert a paracrine effect to facilitate anti-inflammation and angiogenesis. These concerted actions boost the highly efficient restoration of ventricular function and structure. The ROS-scavenging medicine-crosslinked biodegradable biomacromolecule hydrogel bearing stemness-maintained microgels can be expanded to diverse tissue engineering and regenerative medicine fields.