Currently, mitochondrial dysfunction caused by oxidative stress is a growing concern in degenerative diseases, notably intervertebral disc degeneration (IVDD). Dysregulation of the balance of mitochondrial quality control (MQC) has been considered the key contributor, while it’s still challenging to effectively harmonize different MQC components in a simple and biologically safe way. Hydrogen gas (H 2 ) is a promising mitochondrial therapeutic molecule due to its bio-reductivity and diffusibility across cellular membranes, yet its relationship with MQC regulation remains unknown. Herein, we propose a mitochondrial ‘Birth-Death’ coordinator achieved by an intelligent hydrogen nanogenerator (Fe@HP-OD), which can sustainably release H 2 in response to the unique microenvironment in degenerated IVDs. Both in vitro and in vivo results prove alleviation of cellular oxidative stress and restoration of nucleus pulposus cells function, thereby facilitating successful IVD regeneration. Significantly, this study for the first time proposes the mitochondrial ‘Birth-Death’ coordination mechanism: 1) attenuation of overactivated mitochondrial ‘Death’ process (UPR mt and unselective mitophagy); and 2) activation of Adenosine 5‘-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial ‘Birth-Death’ balance (mitochondrial biogenesis and controlled mitophagy). These pioneering findings can fill in the gaps in molecular mechanisms for H 2 regulation on MQC homeostasis, and pave the way for future strategies towards restoring equilibrium of MQC system against degenerative diseases.
Incontinence-associated dermatitis (IAD) leads to persistent tissue damage, antibiotic-resistant infections, and neurogenic inflammation, greatly impairing patients' quality of life. Current therapies fail to simultaneously eliminate resistant bacterial biofilms, neutralize alkaline conditions, and break the cycle of ammonia (NH 3 ) regeneration. Here, a piezoelectric gas therapy strategy based on platinum-decorated bismuth molybdate load in gelatin methacrylate (GelMA) hydrogel (Pt@BMO-Gel) is introduced. Under ultrasound excitation, Pt@BMO generates high piezoelectric potential to improve charge separation, selectively adsorbs NH 3 on BMO (001) crystal facets, efficiently degrades NH 3 to normalize pH, and enables sustained release of H 2 and NO for dual antibacterial and anti-inflammatory effects. Mechanistic insights from theoretical calculations show that the Pt (111) and BMO (001) surfaces lower energy barriers for H 2 formation and N─H bond cleavage, conducive to the generation of NO and H 2 . Transcriptomic profiling reveals downregulation of key nitrogen metabolism genes (arcC/hutH) in methicillin-resistant Staphylococcus aureus (MRSA) and disruption of the (p)ppGpp-mediated stringent response, effectively eradicating bacterial persistence via metabolic reprogramming. This study establishes Pt@BMO as an efficient piezoelectric catalyst for wound therapy, presenting a novel approach in medicine that transforms harmful NH 3 into therapeutic H 2 and NO, offering a promising treatment paradigm for infected wounds, such as incontinence-associated dermatitis.
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