Dual-phase SilMA hydrogel: a dynamic scaffold for sequential drug release and enhanced spinal cord repair via neural differentiation and immunomodulation

Spinal cord injury (SCI) is a severe central nervous system disorder that results in significant sensory, motor, and autonomic dysfunctions. Current surgical techniques and high-dose hormone therapies have not achieved satisfactory clinical outcomes, highlighting the need for innovative therapeutic strategies. The DPSH is designed for temporally controlled release of therapeutic agents to reduce inflammation during the acute phase of SCI and to promote neuronal differentiation and axonal regeneration in later stages. The hydrogel’s degradation, in conjunction with PLGA microspheres, enables sequential drug release. Ang-(1–7) is released early to reduce inflammation and protect neurons, followed by the release of neurotrophic factors to promote neuronal differentiation and axonal regeneration.

• 1
  Ang-(1–7) significantly induced M2 microglia polarization by 1.8-fold (p < 0.0001), effectively reducing inflammation.
• 2
  NT-3 enhanced neural stem cell differentiation into neurons by 3.6-fold (p < 0.0001).
• 3
  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.