Abstract
Low back pain represents the highest burden of musculoskeletal diseases worldwide and intervertebral disc degeneration is frequently associated with this painful condition. Even though it remains challenging to clearly recognize generators of discogenic pain, tissue regeneration has been accepted as an effective treatment option with significant potential. Tissue engineering and regenerative medicine offer a plethora of exploratory pathways for functional repair or prevention of tissue breakdown. However, the intervertebral disc has extraordinary biological and mechanical demands that must be met to assure sustained success. This concise perspective review highlights the role of the disc microenvironment, mechanical and clinical design considerations, function vs mimicry in biomaterial‐based and cell engineering strategies, and potential constraints for clinical translation of regenerative therapies for the intervertebral disc.
Highlights
The results demonstrated that cell-matrix interactions play a crucial role in gaining and maintaining a regenerative phenotype and activity; mimicking the ECM structure alone may not be sufficient without mimicking its functional cellular microenvironment
Several biomaterial strategies exist for tissue-engineered intervertebral disc (IVD) repair, replacement, and regeneration
Once a biomaterial is injected into the IVD, it risks extrusion and reherniation due to significant mechanical loads that persist in normal daily activities, which could exacerbate the clinical condition, and risk further complications
Summary
Low back and neck pain is associated with the highest burden of musculoskeletal disorders and is a leading cause of global disability with tremendous social and economic impact.[1,2] It remains clear that the efficacy of operative and nonoperative treatment requires patients with specific indications and precise diagnosis.[3,4,5] precision diagnosis is commonly lacking for patients with discogenic back pain and multiple spinal disorders which can have complex definitions and interacting structural, biological, and inflammatory sources of pain.[6,7,8,9]. It needs to be considered that all animal models have limitations and generally do not reproduce the mechanisms of human disc degeneration or herniation.[59,121,122] Animals experiencing spontaneous disc degeneration or herniation such as certain canine breeds may represent attractive models for evaluation of new therapies.[123] Some devices for AF repair such as Barricaid, NuCore, Neudisc, DiscCell, DASCOR, BioDisc, and NucleoFix have been developed and approved for clinical use; none of the currently available devices promote tissue regeneration and their efficacy has yet to be demonstrated fully.[50] Ideal intraoperative AF and NP repair methods would prevent reherniation, seal the remaining defects, restore biomechanical function, and reduce the likelihood of recurrent pain.[124]. In comparison to more invasive surgery such as intraoperative repair/replacement, the added advantage of injectable delivery is the reduced volume of material; there needs to be a benefit over risk of possible progressive degeneration which has been observed after IVD puncture.[7,12]
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