Injectable Collagen–Genipin Gel for the Treatment of Spinal Cord Injury: In Vitro Studies

Spinal cord injury (SCI) often results in a cavitary lesion, contained within the dura, which involves only a portion of the cord. Injectable biopolymers are an attractive treatment option for SCI to re‐establish cell migratory pathways within the lesion while minimizing the collateral damage attendant to an open surgical procedure. In this study we evaluate a thermoresponsive soluble collagen gel incorporating genipin, an amine reactive covalent cross‐linker with low cytotoxicity and fluorogenic attributes. Unlike previous studies, genipin is being investigated as an in situ covalent cross‐linker that will continue to act on the gel after injection. Physical characterization studies show that the addition of genipin provides control over the mechanical and degradative behavior of the gel, to meet design specifications of an injectable material for neural tissues. Additionally, an improved in situ assay to predict the extent of cross‐linking reaction is investigated. Encapsulation of mesenchymal stem cells (MSCs) in collagen–genipin gels show the gels support cell viability and proliferation, and thus serve as a cell delivery vehicle. Neural stem cells are found to be more sensitive to genipin, with respect to toxicity, as compared to MSCs. From our studies, 0.25‐0.5 mM is an appropriate genipin concentration to use for an in situ forming scaffold capable of delivering cells and therapeutic agents.