Title : Injectability analysis of an alginate-based hydrogel for stem cell therapy in Inter Vertebral Disc (IVD) injury treatment
Abstract:
Inter Vertebral Disc (IVD) injury is a major factor contributing to lower back pain, which is believed to affect up to 80% of the general population. Alginate could be a low-cost and effective solution for IVD injury in clinical settings, but its mechanical properties need further optimization for more efficient applications. Alginate hydrogels are widely studied because they can be easily cross-linked and because researchers can control their cross-linking and injection times.
Literature has established alginate as an effective treatment for IVD injury. Tan et al. (2021) investigated the potential of cRGD and AG73, which are integrin- and syndecan-binding peptides, respectively, to restore nucleus pulposus (NP) cells. The NP region is essential for disc function but deteriorates chronically with age, contributing to spinal degeneration. By adding cRGD and AG73 peptides to alginate, the researchers observed significant increases in NP- specific markers, including proteoglycan production and N-cadherin expression. The dual-ligand hydrogels promoted a rounded NP cell shape, especially in 3D cultures, where clustering mimicked the natural microenvironment. These findings reinforce the importance of ligand presentation, suggesting that peptide-functionalized alginate hydrogels could be ideal for IVD repair.
Injectability, a mechanical property based on a material's viscosity that measures how easily a liquid can be injected through a syringe, is important to consider in clinical alginate hydrogel applications. Muir et al. (2024) further explore this by analyzing the injectability of a hyaluronic acid-based granular hydrogel with zirconium oxide (ZrO2). This hydrogel demonstrated excellent injectability, self-healing behavior, and mechanical stability suitable for IVD applications. When injected into a goat model of disc degeneration, the hydrogel restored disc height and prevented further collapse. Its radiopacity, or the ability to absorb UV light or X- rays, enabled in vivo imaging using fluoroscopy and CT. This study highlights the need for hydrogels that are both mechanically functional and clinically traceable, supporting my project’s focus on the injectability and delivery efficiency of alginate-based hydrogels.
In this project, I investigated the synthesis, crosslinking, and performance testing of alginate hydrogels to evaluate their injectability, cellular compatibility, and potential use in IVD regeneration. I prepared 1 mL of 1% alginate hydrogel and injected it using an injection device set to a 300 μL/min rate through two different needle gauges: 19G and 25G. As a control, I also tested 1 mL of pure dPBS. Results indicated that alginate was significantly less injectable than dPBS in 19G needles (p<0.01), but there was no significant difference in injectability in 25G needles (p>0.05). These findings demonstrate the potential of alginate to be injected using 25G needles in clinical applications and are further validated by the Muir et al. (2024) paper, which used similar extrusion setups to assess injectability.
There is a large clinical need for minimally invasive, biomaterial-based therapies that can restore disc function and prevent further degeneration. In the future, the results of this project could be applied to using an alginate-based hydrogel to inject into the disc of either a joint dealing with an IVD or with rheumatoid arthritis.
