Acid Neutralization by Composite Lysine Nanoparticles for Spinal Cord Injury Recovery through Mitigating Mitochondrial Dysfunction.
Qiuchen WangLu GeJiali GuoHaijuan ZhangTianling ChenFeifei LianLei LiYun XuJinyu XuNuo ChenYu ZhangZhanwei RuanZhou-Guang WangHongyu ZhangLiangliang YangPublished in: ACS biomaterials science & engineering (2024)
After spinal cord injury (SCI), significant alterations in the tissue microenvironment lead to mitochondrial dysfunction, inducing apoptosis and inhibiting the remodeling of neural circuits, thereby impeding recovery. Although previous studies have demonstrated a marked decrease in pH at the injury site, creating an acidic microenvironment, the impact of improving this acidic microenvironment on SCI recovery has not been investigated. This study prepared a lysine@hollow mesoporous silica nanoparticle/gelatin methacrylate (GelMA) (L@H/G) composite hydrogel. The L@H/G composite hydrogel was demonstrated to release lysine and efficiently improve the acidic microenvironment slowly. Significantly, the composite hydrogel reduced cell apoptosis, promoted nerve regeneration, inhibited glial scar formation, and ultimately enhanced motor function recovery in mice with SCI. Mechanistically, the L@H/G hydrogel improved the mitochondrial tricarboxylic acid (TCA) cycle and fatty acid metabolism, restoring energy supply and facilitating mitochondrial function recovery. To the best of our knowledge, this is the first report confirming that improving the acidic microenvironment could promote SCI repair, providing a potential therapeutic strategy for SCI.
Keyphrases
- spinal cord injury
- stem cells
- drug delivery
- hyaluronic acid
- wound healing
- neuropathic pain
- spinal cord
- ionic liquid
- tissue engineering
- oxidative stress
- fatty acid
- healthcare
- cell proliferation
- type diabetes
- signaling pathway
- adipose tissue
- skeletal muscle
- mass spectrometry
- metabolic syndrome
- amino acid
- high resolution
- simultaneous determination
- molecularly imprinted