Living and Injectable Porous Hydrogel Microspheres Promoting Inflammation Modulation and Extracellular Matrix Remodeling for Intervertebral Disc Regeneration

Oct 13, 2025ACS applied materials & interfaces

Injectable Porous Hydrogel Microspheres That Promote Inflammation Control and Tissue Repair for Spinal Disc Regeneration

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

GMPB (+BMSCs) microspheres demonstrated over 63% scavenging rates for reactive oxygen species compared to controls.

Injectable hydrogel microspheres were created to improve the conditions for stem cell therapy in degenerated intervertebral discs.
The microspheres exhibited excellent compatibility and promoted cell adhesion by mimicking the natural environment of the extracellular matrix.
Incorporating Prussian blue nanozymes conferred significant antioxidant and anti-inflammatory properties to the microspheres.
Microspheres loaded with bone marrow stem cells supported cell growth and protected against damage from oxidative stress.
GMPB (+BMSCs) microspheres contributed to maintaining disc height and hydration while reducing signs of degeneration.
Lower Pfirrmann grades indicated improved structural integrity of the extracellular matrix in treated discs.

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Intervertebral disc degeneration (IDD) remains a major cause of chronic low back pain, with limited options for effective disease modification. The harsh microenvironment of the degenerated disc, characterized by excessive oxidative stress and inflammation, severely impairs the survival and reparative potential of transplanted stem cells. Here, we present an injectable, porous and multifunctional hydrogel microsphere platform (GMPB) designed to remodel the local niche and enhance stem cell-based disc regeneration. Microspheres were fabricated from a composite matrix of gelatin methacryloyl (GelMA) and chondroitin sulfate methacryloyl (ChsMA), conferring excellent cytocompatibility and cell-adhesive properties while mimicking key aspects of the native extracellular matrix. Incorporation of Prussian blue (PB) nanozymes endowed the microspheres with potent broad-spectrum reactive oxygen species (ROS) scavenging and anti-inflammatory activity, as evidenced by significantly higher DPPH, ABTS, and ·OH radical scavenging rates (all >63%) compared to controls. BMSCs-loaded GMPB (named GMPB (+BMSCs)) microspheres supported robust cell proliferation and protected transplanted cells against ROS-induced injury., GMPB (+BMSCs) microspheres effectively preserved disc height, maintained matrix hydration (high T2-weighted MRI signal), and reduced histological degeneration, as indicated by lower Pfirrmann grades and improved extracellular matrix integrity. Collectively, these results highlight GMPB (+BMSCs) microspheres as a promising and versatile platform that synergistically integrates biomimetic support, redox modulation, and efficient cell delivery to establish a regenerative microenvironment for intervertebral disc repair and broader tissue engineering applications. in vitro In vivo

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Living and Injectable Porous Hydrogel Microspheres Promoting Inflammation Modulation and Extracellular Matrix Remodeling for Intervertebral Disc Regeneration

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