Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs

Abstract

Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation.

Oxygen metabolism-balanced engineered hydrogel microspheres promote the regeneration of the nucleus pulposus by inhibiting acid-sensitive complexes

“…Therefore, the nanoparticles that are currently in use rely on transport carriers to improve their injection efficiency and targeting. Organometallic frameworks and hydrogels are currently used as transport carriers for IVDD treatment; however, there are still significant drawbacks [ 32 , 33 ]. For example, compression tends to lead to the collapse of the overall structure of large hydrogels and causes subsequent complications [ 34 ].…”

Enhanced Intervertebral Disc Repair via Genetically Engineered Mesenchymal Stem Cells with Tetracycline Regulatory System

“…If the multiple MSC injections are required to overcome these issues, it must be considered that additional inflammatory responses and injuries may occur during the injection process [33]. To enhance the viability of MSCs within the human intervertebral disc (IVD) and induce stable differentiation, applying bio-scaffolds or a chemo-attractant delivery system can be further considered [89,90].…”

Reviving Intervertebral Discs: Treating Degeneration Using Advanced Delivery Systems

“…However, SDF-1α is easily degraded by MMP, which may hinder its practical application. Therefore, designing reasonable biomaterials to deliver SDF-1α to continuously recruit MSCs and promote IVD regeneration is a feasible solution, and researchers have made many attempts in this regard. , In previous studies, the delivery of this chemokine using a thermosensitive hydrogel as a carrier has been shown to significantly increase the number of MSCs migrating to the IVD . However, the release of SDF-1α from the hydrogel was relatively slow, which resulted in a longer time being required to recruit high chemotactic gradient MSCs.…”