Preserving the Immune‐Privileged Niche of the Nucleus Pulposus: Safeguarding Intervertebral Discs from Degeneration after Discectomy with Synthetic Mucin Hydrogel Injection

Abstract Intervertebral disc (IVD) herniation is a prevalent spinal disorder, often necessitating surgical intervention such as microdiscectomy for symptomatic relief and nerve decompression. IVDs comprise a gel‐like nucleus pulposus (NP) encased by an annulus fibrosus (AF), and their avascular nature renders them immune‐privileged. Microdiscectomy exposes the residual NP to the immune system, precipitating an immune cell infiltration and attack that exacerbates IVD degeneration. While many efforts in the tissue engineering field are directed toward IVD regeneration, the inherently limited regenerative capacity due to the avascular and low‐cellularity nature of the disc and the challenging mechanical environment of the spine often impedes success. This study, aiming to prevent IVD degeneration post‐microdiscectomy, utilizes mucin‐derived gels (Muc‐gels) that form a gel at the surgical site, inspired by the natural mucin coating on living organisms to evade immune reorganization. It is shown that type I macrophages are present in severely degenerated human discs. Encapsulating IVDs within Muc‐gels prevents fibrous encapsulation and macrophage infiltration in a mouse subcutaneous model. The injection of Muc‐gels prevents IVD degeneration in a rat tail IVD degeneration model up to 24 weeks post‐operation. Mechanistic investigations indicate that Muc‐gels attenuate immune cell infiltration into NPs, offering durable protection against immune attack post‐microdiscectomy.