The extracellular matrix is a complex structure of molecules generated and maintained by cells to support themselves and determine the physical properties of a tissue, such as load-bearing capacity or elasticity. The extracellular matrix changes with age in ways that are not fully explored, but which harm cells and tissue function. Comparatively little effort is focused on finding ways to repair the aged extracellular matrix, in part because it seems a hard problem. There are few points of intervention that can be as simple as the one noted here, where delivering a novel substitute molecule allows it to be incorporated into the matrix to improve matters. In most cases, providing the raw materials is not enough; there are issues of cell activities, problematic alterations to existing structures, or toxic debris from chemical interactions in the matrix, to pick a few of the many issues.
Intervertebral disc degeneration (IDD) accounts for nearly half of the cases of low back pain (LBP), a leading cause of disability worldwide. The progression of IDD is characterized by decreased intervertebral disc height and water content in the nucleus pulposus (NP) tissue which lies in the center of the intervertebral disc and is surrounded by annulus fibrosus (AF).
A key change to the NP tissue along IDD development is the increasing loss of glycosaminoglycan (GAG) polysaccharides. GAGs are a main component of the gel-like extracellular matrix (ECM) that maintains the morphology and phenotypes of NP cells (NPCs). Although replenishing GAGs has emerged as a promising strategy, its efficacy remains unclear, with hardly any clinical success achieved. Recent findings have raised questions that the NP tissue under degeneration is maintained as a catabolic microenvironment by the elevated presence of enzymes that can degrade native GAGs. An alternative approach is to implant a biomaterial substitute of GAGs - serving as a glue to the damaged ECM of NP. This glue material should avoid recognition by the enzymes in the pathological niche, and meanwhile, mimic native GAGs in exerting specific bioactivities to support NPC functionality.
Accordingly, we synthesize a glucomannan octanoate (GMOC) with robust resistance to ECM-cleaving enzymes. GMOC injected into the degenerated intervertebral disc leads to NP tissue regeneration in a rat and a rabbit model, which represent two clinical scenarios of pre-surgical intervention and post-surgical regeneration of IDD, respectively. In summary, we report enriching the ECM with a glycan glue as a mechanism to promote NP regeneration for IDD treatment.
Link: https://doi.org/10.1...467-025-58946-5
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