Long-term pre-clinical evaluation of an injectable chitosan nanocellulose hydrogel with encapsulated adipose-derived stem cells in an ovine model for IVD regeneration

摘要

The potential therapeutic benefit of adipose-derived stem cells (ASCs) encapsulated in an injectable hydrogel for stimulating intervertebral disc (IVD) regeneration has been assessed by a number of translational and preclinical studies. However, previous work has been primarily limited to small animal models and short-term outcomes of only a few weeks. Long-term studies in representative large animal models are crucial for translation into clinical success, especially for permanent stabilization of major defects such as disc herniation. An injectable chitosan carboxymethyl cellulose hydrogel scaffold loaded with ASCs was evaluated regarding its intraoperative handling, crosslinking kinetics, cell viability, fully-crosslinked viscoelasticity, and long-term therapeutic effects in an ovine model. Three IVDs per animal were damaged in 10 sheep. Subcutaneous adipose tissue was the source for autologous ASCs. Six weeks after IVD damage, two of the damaged IVDs were treated via ASC-loaded hydrogel injection. After 12 months following the implantation, IVD disc height and histological and cellular changes were assessed. This system was reliable and easy to handle intraoperatively. Over 12 months, IVD height was stabilized and degeneration progression significantly mitigated compared to untreated, damaged IVDs. Here we show for the first time in a large animal model that an injectable chitosan carboxymethyl cellulose hydrogel system with encapsulated ASCs is able to affect long-term stabilization of an injured IVD and significantly decrease degeneration processes as compared to controls.