Injectable Thermoresponsive Microgels Encapsulate and Precondition Nucleus Pulposus Cells for Intervertebral Disc Regeneration
Wensen Jiang, Namdev More, Melissa Chavez, Jacob T Wechsler, Sarah Mohyeddinipour, Tiffany Lee, Wei Huang, Giselle Kaneda, Lei Mou, Thomas Spaeter, Julia Sheyn, Changlu Xu, Victoria Yu, Chloe Castaneda, Ethan Ha, Wafa Tawackoli, Linda EA Kanim, Oksana Shelest, Hyun W Bae, Samad Ahadian, Mehmet R. Dokmeci, Ali Khademhosseini, Dror Seliktar, Dmitriy SheynAbstract
Chronic lower back pain (LBP), a leading cause of disability affecting over half a billion people globally, is often linked to intervertebral disc (IVD) degeneration. Current treatments, like surgery and pain management, fail to address the IVD degeneration that is associated with the deterioration of the nucleus pulposus (NP). We aim to develop an injectable cell therapy for LBP using human nucleus pulposus cells (NPCs) encapsulated in hydrogel microparticles (microgels) as a cell delivery vehicle. The thermoresponsive hydrogels enabled cell encapsulation and preconditioning without the use of ultraviolet irradiation or cytotoxic cross-linkers. The in vitro preconditioning maintained cell viability and promoted type 2 collagen secretion. In a rat IVD degeneration model, NPCs were encapsulated in fibrinogen-based hydrogels at 10 million cells/mL, preconditioned for 7 days, and injected into degenerated discs. Evaluations of disc height using μCT, gene expression using RT-qPCR on the harvested IVD and dorsal root ganglion (DRG), and histology showed that NPC-loaded microgels increased IVD height and reduced pain-related gene expressions compared to controls. Our findings demonstrate that NPC-loaded microgels have the potential to alleviate pain and regenerate IVDs, suggesting minimally invasive treatment for discogenic LBP and future clinical applications.