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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.
Sec. Biomaterials
Volume 12 - 2024 | doi: 10.3389/fbioe.2024.1501488
This article is part of the Research Topic Advanced Functional Materials for Disease Diagnosis, Drug Delivery and Tissue Repair View all 10 articles

Dual-Phase SilMA Hydrogel: A Dynamic Scaffold for Sequential Drug Release and Enhanced Spinal Cord Repair via Neural Differentiation and Immunomodulation

Provisionally accepted
Ruizhi  Zhang Ruizhi Zhang 1Mingzhe  Zhang Mingzhe Zhang 1*Lu  Chen Lu Chen 1*Linlin  Jiang Linlin Jiang 1*Chenbo  Zou Chenbo Zou 1*Na  Li Na Li 1*Hengxing  Zhou Hengxing Zhou 1*Shiqing  Feng Shiqing Feng 1,2*
  • 1 Qilu Hospital, Shandong University, Jinan, China
  • 2 The Second Hospital of Shandong University, Jinan, Shandong Province, China

The final, formatted version of the article will be published soon.

    Spinal cord injury (SCI) is a severe central nervous system disorder that leads to significant sensory, motor, and autonomic dysfunctions. Despite progress in surgical techniques and high-dose hormone therapies, clinical outcomes remain inadequate, underscoring the need for innovative therapeutic approaches. In this study, we developed a Dual-Phase Silk Fibroin Methacryloyl (SilMA) hydrogel scaffold (DPSH), incorporating PLGA microspheres encapsulating neurotrophin-3 (NT-3) and angiotensin (1-7) (Ang-(1-7)). This advanced scaffold is designed to provide a temporally controlled release of therapeutic agents, aimed at reducing inflammation during the acute phase of SCI and promoting neuronal differentiation and axonal regeneration in subsequent stages, thereby enhancing neural repair. Comprehensive characterization revealed that the DPSH possesses a highly porous architecture, appropriate mechanical properties for spinal cord tissue, and stability unaffected by the incorporation of microspheres and drugs. In vitro studies showed that Ang-(1-7) significantly induced M2 microglia polarization by [1.8-fold] (p < 0.0001), reducing inflammation, while NT-3 enhanced neural stem cell differentiation into neurons by [3.6-fold] (p < 0.0001). In vivo, the DPSH group exhibited significantly higher Basso Mouse Scale (BMS) scores (p < 0.0001), enhanced motor function, reduced astrocyte scarring by [54%] (p < 0.05), and improved neuronal survival and regeneration. These findings underscore the therapeutic potential of the DPSH scaffold for SCI repair, offering a novel strategy to enhance neural recovery by combining immunomodulation and neuroregeneration.

    Keywords: spinal cord injury, SilMA hydrogel, Neurotrophin-3, Angiotensin-(1-7), Immunomodulation, neural differentiation

    Received: 25 Sep 2024; Accepted: 30 Oct 2024.

    Copyright: © 2024 Zhang, Zhang, Chen, Jiang, Zou, Li, Zhou and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Mingzhe Zhang, Qilu Hospital, Shandong University, Jinan, China
    Lu Chen, Qilu Hospital, Shandong University, Jinan, China
    Linlin Jiang, Qilu Hospital, Shandong University, Jinan, China
    Chenbo Zou, Qilu Hospital, Shandong University, Jinan, China
    Na Li, Qilu Hospital, Shandong University, Jinan, China
    Hengxing Zhou, Qilu Hospital, Shandong University, Jinan, China
    Shiqing Feng, Qilu Hospital, Shandong University, Jinan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.