Bioactive Materials | Conductive Hydrogel Integrated with 3D-MSCs Apoptotic Bodies Alleviates Spinal Cord Injury through Immunomodulation and Mitigates Neuronal Thermal Hypoesthesia

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Spinal cord injury (SCI) is a serious condition that affects the central nervous system. Current clinical interventions are insufficient to address the far-reaching consequences of spinal cord injury, highlighting an urgent need for alternative therapeutic approaches. In recent years, the local delivery of extracellular vesicles (EVs) via hydrogels has emerged as a potential method for treating spinal cord injuries, and conductive hydrogels can further promote spinal cord repair by establishing functional connections between neurons.However, enhancing the bioactivity of electric vehicles and optimizing hydrogel-based therapies remain significant challenges. In this study, MXene nanosheets endowed the composite hydrogel with excellent conductivity. Bone marrow mesenchymal stem cells (BMSCs) were cultured in a three-dimensional suspension to form spheroids, which were then induced to undergo apoptosis to isolate apoptotic bodies (ABs). Subsequently, 3D-ABs were integrated into gelatin methacryloyl (GelMA) hydrogels containing MXene nanosheets.It provides sustained release in vivo. In addition, the composite hydrogel offers mechanical support and mimics the electrical transmission characteristics of neurons. After local injection into mice with spinal cord injury, the composite hydrogel effectively fills the lesion cavity, promotes the reconstruction of functional neural connections, inhibits neuroinflammation, and alleviates neuronal thermal damage due to its conductive components and apoptotic vesicles. This novel injectable composite hydrogel represents a promising therapeutic option for spinal cord injury repair.

The study, titled "3D-MSCs apoptotic body-integrated conductive hydrogel reduces SCI via immunoregulation and neuronal pyroptosis alleviation," was published in Bioactive Materials.

Summary :

After spinal cord injury (SCI), uncontrolled inflammation and neuronal death are two major obstacles to functional recovery. A research team from Wenzhou Medical University published a study in Bioactive Materials, designing a conductive and bioactive composite hydrogel to address SCI repair. The researchers first cultured bone marrow mesenchymal stem cells (BMSCs) in a 3D suspension environment to form spheroids, then induced apoptosis and isolated 3D apoptotic bodies (3D-ABs). These 3D-ABs exhibited stronger bioactivity than conventional 2D-cultured versions, packed with proteins and miRNAs. Next, they encapsulated MXene nanosheets and these 3D-ABs into a gelatin hydrogel, creating an injectable, conductive, and sustained-release AMG hydrogel.

In a mouse model of spinal cord hemisection, the AMG hydrogel showed remarkable results. By day 28 post-injury, the AMG group exhibited significantly improved hindlimb locomotion, with Basso Mouse Scale (BMS) scores rising from 2.5 (SCI group) to over 5, nearly full recovery of motor-evoked potential (MEP) amplitudes, and reduced gastrocnemius muscle atrophy. Single-cell sequencing and mechanistic studies revealed the underlying mechanisms:

This "physical bridging + biological regulation" dual strategy effectively tackled both the acute inflammatory storm and chronic neuroregeneration challenges in SCI.

Reference News:

DOI: 10.1016/j.bioactmat.2026.01.043