Torabi Rahvar, ParisaParisaTorabi RahvarSchlagenhof, Leon MaxLeon MaxSchlagenhofAbdekhodaie, M. J.M. J.AbdekhodaieGantenbein, BenjaminBenjaminGantenbein0000-0002-9005-06552024-10-252024-10-252023https://boris-portal.unibe.ch/handle/20.500.12422/171432INTRODUCTION Low back pain is a common and widespread health problem affecting a significant percentage of adults (up to 80%) worldwide1. Mesenchymal stem cells (MSCs) have shown new hope to regenerate the early stages of intervertebral disc degeneration. However, there are debates as to whether transplanted cells in cell suspensions can survive in the harsh environment of degenerated IVDs, which may limit the effectiveness of cell therapy. An appropriate cell delivery system is necessary to ensure the efficacy of MSCs in vivo2. Herein, hybrid injectable microgels based on hyaluronic acid (HA) and collagen type II (COLII) were developed for cell delivery to the IVD, mimicking the polysaccharide-protein composition of the native NP extracellular matrix. The study also uses an ex vivo papain-induced bovine tail disc degeneration model to investigate this cell therapy. EXPERIMENTAL METHODS Tyramine-grafted HA and COLII were prepared using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and n-hydroxysulfosuccinimide (NHS) chemistry3. HA-Tyr and COLII-Tyr were dissolved in phosphate buffered saline (PBS) and mixed at different ratios followed by adding horseradish peroxidase (HPR). The polymer solution was extruded through a syringe pump and microdroplets were generated using a flicking-based vibrating nozzle system. The droplets fell into a H2O2 solution and formed microgels. The hydrogels were characterized in terms of their mechanical properties and gelation time. The shape and size distribution of the microgels were analyzed using phase contrast and scanning electron microscopy (SEM). RESULTS AND DISCUSSION With this novel approach, uniform microgels could be fabricated with variable size in the range of 300–500 µm and narrow distribution in all compositions (Figure 1). We are currently optimizing the injection conditions of microgels into NP tissue as a function of microgel composition and needle gauge. CONCLUSION This study presents the initial optimization process to produce enzymatically crosslinked HA-COLII microgels. The goal is to utilize these microgels as building blocks mimicking the extracellular matrix for NP tissue regeneration. REFERENCES Wöltje M. et al., Biomimetics. 12;8(2):152, 2023. Xu H. et al., Biofabrication. 31;13(1):015010, 2020. Jooybar E. et al., Acta Biomater. 1;83:233-44, 2019. ACKNOWLEDGMENTS This research was funded by the Council for Development of Stem Cell Sciences and Technologies (#57940), Iran National Science Foundation: INSF (# 99002288) and an SNF-bridge project # 40B2-0_211510/1.en600 - Technology::610 - Medicine & healthconference_item