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This article, reported by Ye Xiaojian and Yu Jiangming from Shanghai Jiao Tong University, essentially upgrades "lactic acid clearance" to "lactic acid metabolic reprogramming". The authors did not merely oxidize lactic acid into pyruvate as in traditional thinking, but further utilized a "orthogonal tandem catalysis" system to continuously convert lactic acid into pyruvate and then into alanine, thereby simultaneously addressing two core issues: on one hand, it reduces the abnormal accumulation of lactic acid within degenerated intervertebral discs and inhibits the activation of NLRP3 inflammasome and inflammatory storm; on the other hand, it generates alanine with antioxidant potential, alleviating the increase in ROS and the aging of nucleus pulposus cells. In other words, this is not merely "reducing lactic acid", but rewriting the fate of lactic acid in the lesion microenvironment.
From the perspective of material design, the authors loaded LDH, ALT and their substrates into mesoporous silica nanoparticles, which were then encapsulated into injectable hydrogel microspheres, and introduced SDF-1α to recruit endogenous stem cells. Finally, they constructed a local reactor with functions of metabolic regulation, microenvironment repair, and cell recruitment. This system can efficiently clear lactic acid in vitro and continuously generate alanine in vivo, maintaining a metabolic reprogramming window of approximately 4 weeks, which is well aligned with the pathological process of early continuous deterioration of intervertebral disc degeneration. The authors further demonstrated that this strategy not only can suppress inflammation and aging signals, but also promotes nucleus pulposus-like tissue regeneration and restores the biomechanical properties of the new tissue to a level close to normal.
The most interesting part of this article is not merely creating an "injection microsphere" or "enzyme catalytic material", but proposing a very inspiring therapeutic logic: For metabolic degenerative diseases, the truly effective intervention is not necessarily a single-point blockade, but rather the conversion of harmful metabolites into molecules beneficial for repair. This "from metabolic waste to repair substrate" thinking is clearly a step further than traditional anti-inflammatory, antioxidant or simple cell supplementation, and is closer to the core of "pathological microenvironment remodeling" in regenerative medicine.
The related research was published in Nature Communications under the title "Lactate metabolism reprogramming through orthogonal tandem catalysis to reverse intervertebral disc degeneration".
