Platelet-Rich Plasma-Loaded Dual-Network Hyaluronic Acid-Based Hydrogel as a Bioactive Scaffold for Enhancing Nerve Regeneration in Spinal Cord Injury

This study developed dual-network hyaluronic acid (<i>dn</i>HA) hydrogels incorporating platelet-rich plasma (PRP) as bioactive scaffolds for spinal cord injury (SCI) repair. Polyethylene glycol diglycidyl ether-cross-linked hyaluronic acid (HA-PEGDE), methacrylated HA (HA-Mac), maleimide-modified HA (HA-Mal), and thiol-modified HA (HA-SH) were synthesized. The <i>dn</i>HA hydrogels consisted of a primary HA-PEGDE network and a secondary HA-Mac or HA-Mal/HA-SH network. The physicochemical and rheological properties of the <i>dn</i>HA hydrogels were characterized. Scanning electron microscopy (SEM) revealed that HP_E0.5KH_MalH_SH and HP_E2KH_MalH_SH formed a porous and aligned fibrous structure, suggesting the potential for sustained release. Swelling and degradation studies confirmed stability, while rheological analysis showed a mechanical strength of ∼1000 Pa, mimicking neural extracellular matrices. Biocompatibility was comparable to Restylane Lyft. Furthermore, in a mouse SCI model, PRP-loaded HP_E0.5KH_MalH_SH hydrogels significantly improved Basso-Beattie-Bresnahan (BBB) scores, achieving near-complete recovery at 8 weeks. These PRP-loaded <i>dn</i>HA hydrogels function by locally retaining growth factors within the hydrogel matrix to promote regeneration rather than releasing PRP rapidly. Their aligned fibrous structure and controlled release properties show promise for nerve regeneration. Further studies are warranted to elucidate the underlying mechanisms and optimize their clinical application in SCI treatment.