Catalytically Triggered and BMSCs-Laden Piezoelectric Injectable Hydrogel for Intervertebral Disc Degeneration Therapy

Abstract

Intervertebral disc degeneration (IDD) is a major cause of low back pain, and injectable hydrogels offer a promising minimally invasive treatment. However, current hydrogels rely on exogenous triggers or have unstable shear-thinning properties, limiting their therapeutic use. We developed a catalytically triggered piezoelectric injectable hydrogel loaded with bone marrow-derived mesenchymal stem cells (BMSCs) for synergistic IDD regeneration. This system uses a gelatin methacryloyl (GelMA) and diacrylate-functionalized Pluronic F-127 (PF127-DA) composite that rapidly crosslinks via a Fenton-like redox reaction between ferrous gluconate and ammonium persulfate, eliminating the need for external triggers. The hydrogel contains poly(L-lactic acid) (PLLA) piezoelectric fibers and BMSCs. Under ultrasound stimulation, PLLA fibers generate piezoelectric microcurrents that stimulate BMSCs, significantly increasing transforming growth factor-beta (TGF-β) secretion. This promotes BMSCs differentiation into nucleus pulposus-like cells and recruits endogenous nucleus pulposus cells, enhancing matrix synthesis. This platform integrates injectable delivery, in situ piezoelectric stimulation, and biological factor regulation, providing a novel and effective strategy for disc regeneration.

Graphical Abstract

An injectable piezoelectric hydrogel laden with BMSCs and PLLA short fibers was developed, in which ultrasound-activated piezoelectric currents stimulate TGF-β secretion to direct BMSCs toward nucleus pulposus-like differentiation and enhance matrix synthesis. This integrated approach for IDD treatment thus combines minimally invasive delivery, spatiotemporally precise stimulation and in situ regenerative efficacy.

Keywords

Intervertebral disc degeneration / Multifunctional hydrogel / Piezoelectric stimulation / Intervertebral disc regeneration

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Funding

Lingang Laboratory(LGL5925-20)

National Natural Science Foundation of China(32401133)

Shanghai Municipal Commission of Science and Technology(24YF2701400)

Donghua University 2025 Cultivation Project of Discipline Innovation(xkcx-202512)

National Key Clinical Specialty Discipline Construction Program of China(Z155080000004)

Shanghai Health and Family Planning System Excellent Young Medical Talents Training Program(2018YQ32)

RIGHTS & PERMISSIONS

Donghua University, Shanghai, China

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