Peptide-Activated ECM-Mimicking Channeled OPF Cryogel Scaffold for Spinal Cord Lesion Bridging: Development and Pilot...

Oligo[poly(ethylene glycol) fumarate] (OPF) is an efficient gel-forming macromer for challenging tissue engineering applications, including repair of the spinal cord (SC) after complete lesion. Existing OPF-derived SC-bridging hydrogels are being applied with cellular products and/or electrical stimulation to promote regeneration. A novel biologics-free composite OPF hydrogel was designed as a ready-to-use neuroactive scaffold with defined (bio-)chemical, porous structure, and multi-channel system to support cellular/axonal growth. It was constructed as a highly permeable macroporous cryogel and activated with compositions of IKVAV, RGD, GHK, and LRE cytoadhesive/signaling peptide derivatives via cyclodextrin-adamantane affinity binding to create a synthetic ECM analog. The four-peptide composition promoted neural cell growth and morphological differentiation in vitro. Relationships between OPF macromer concentration, channel diameter, and biomechanical properties were established, enabling development of OPF scaffold with balanced architecture. Its longitudinal compressive strength was adjusted to SC-bridging conditions by comparison with SC explants. A mini-pig SC transection and bridging model was optimized to perform a pilot in vivo study that showed scaffold biointegration, structural maintenance, and host cell infiltration following acute implantation. These findings demonstrate the potential of OPF cryogel scaffold for SC repair and provide a strong foundation for studying its long-term effects upon complete SC lesion.