Injectable Immune-Regulating Mesenchymal Stem Cells Hydrogel for Localized Scleroderma Treatment

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Nanotechnology

Background:

• Mesenchymal stem cells (MSCs) hold promise for scleroderma treatment, but their efficacy is limited by the local microenvironment.
• Bioactive hydrogels are needed to enhance MSCs therapy with anti-inflammatory, antioxidant, and pro-angiogenic properties for scleroderma.

Purpose of the Study:

• To develop an injectable hydrogel incorporating MSCs and polyphenol nanozymes for localized scleroderma treatment.
• To investigate the hydrogel's ability to modulate the immune response, scavenge reactive oxygen species (ROS), and support MSCs function.
• To evaluate the therapeutic potential of the hydrogel in a mouse model of scleroderma.

Main Methods:

• Constructed an injectable, self-healing hydrogel using a dynamic Schiff reaction, incorporating MSCs and natural polyphenol-based nanozymes.
• Assessed the hydrogel's physicochemical properties, including injectability, self-healing, and tissue adhesion.
• Evaluated the hydrogel's biocompatibility, antioxidant capacity (ROS scavenging), anti-inflammatory effects, and ability to promote MSCs antifibrosis, migration, and neovascularization in vitro.
• Tested the therapeutic efficacy in a mouse scleroderma model, analyzing lesion recovery, inflammation, fibrosis, and angiogenesis.

Main Results:

• The Schiff reaction-based hydrogel exhibited injectability, self-healing, and tissue adhesion.
• Polyphenol nanozymes enhanced ROS scavenging and anti-inflammatory properties, facilitating macrophage transformation.
• The hydrogel provided a supportive 3D environment for MSCs, promoting antifibrosis, vascular endothelial cell migration, and neovascularization in vitro.
• In vivo studies showed accelerated scleroderma lesion recovery, reduced pro-inflammatory and fibrotic factors, enhanced angiogenesis, and improved skin appendage remodeling in mice.

Conclusions:

• The injectable polyphenol nanozyme MSCs hydrogel demonstrates significant potential for treating localized scleroderma.
• This biomaterial strategy effectively modulates the local microenvironment to enhance MSCs therapeutic functions.
• The developed hydrogel offers a promising therapeutic approach for scleroderma management by combining biomaterial engineering with regenerative medicine principles.