Nanozymes represent a class of nanomaterials with enzyme-like catalytic activity, capable of scavenging reactive oxygen species (ROS) to enhance tissue repair in regenerative medicine. Among these, cerium oxide nanoparticles (CeO2 NPs) and platinum nanoparticles (Pt NPs) have demonstrated significant potential due to their unique redox properties and ability to mimic natural antioxidant enzymes such as catalase, superoxide dismutase, and peroxidase. Their application in ischemic and aged tissue models highlights their therapeutic potential in mitigating oxidative stress, a key barrier to effective tissue regeneration.

The catalytic mechanisms of nanozymes are rooted in their surface chemistry and redox-active sites. CeO2 NPs exhibit mixed valence states (Ce3+ and Ce4+) on their surface, enabling them to switch between oxidation and reduction states. This property allows CeO2 NPs to catalytically decompose superoxide radicals (O2•−) and hydrogen peroxide (H2O2) into less harmful species. The Ce3+/Ce4+ ratio is critical, as a higher Ce3+ content enhances superoxide dismutase-like activity, while Ce4+ dominance favors catalase-like activity. Pt NPs, on the other hand, primarily exhibit peroxidase-like and catalase-like activities, depending on the pH and ROS environment. Their platinum surface facilitates the breakdown of H2O2 into water and oxygen, reducing oxidative damage in tissues.

Dosing strategies for nanozymes must balance efficacy with safety. Studies indicate that CeO2 NPs at concentrations between 0.1 and 10 µg/mL effectively scavenge ROS without inducing cytotoxicity. Higher doses may lead to pro-oxidant effects, exacerbating tissue damage. Pt NPs, due to their high catalytic efficiency, often require lower doses (0.01–1 µg/mL) to achieve therapeutic effects. The route of administration also influences dosing; localized delivery via injectable hydrogels or scaffolds ensures sustained release and minimizes systemic exposure. Intravenous administration demands precise control over nanoparticle size and surface modification to avoid off-target accumulation.

In ischemic tissue models, nanozymes have shown promise in restoring redox homeostasis and promoting repair. Ischemia-reperfusion injury generates excessive ROS, leading to cell death and impaired healing. CeO2 NPs administered post-ischemia reduce infarct size by up to 40% in cardiac models, while Pt NPs enhance angiogenesis by preserving endothelial function. The mechanisms include suppression of pro-inflammatory cytokines (e.g., TNF-α, IL-6) and activation of pro-survival pathways (e.g., Akt, ERK). In stroke models, nanozymes cross the blood-brain barrier when functionalized with targeting ligands, reducing neuronal apoptosis and improving functional recovery.

Aged tissues present a unique challenge due to chronic oxidative stress and diminished endogenous antioxidant capacity. Nanozymes counteract age-related ROS accumulation, rejuvenating stem cell function and extracellular matrix remodeling. In skeletal muscle regeneration, CeO2 NPs enhance satellite cell proliferation and differentiation, increasing myofiber size by 20–30% in aged mice. Similarly, Pt NPs improve cutaneous wound healing in elderly models by accelerating collagen deposition and epithelialization. The ability of nanozymes to modulate mitochondrial ROS production is particularly beneficial in aging, where mitochondrial dysfunction is a hallmark.

The applications extend to other regenerative contexts, such as diabetic wounds and neurodegenerative diseases. Diabetic ulcers exhibit impaired healing due to persistent oxidative stress. Nanozyme-loaded dressings reduce wound size by 50% compared to controls, attributed to enhanced fibroblast migration and reduced oxidative damage. In neurodegenerative models, CeO2 NPs protect dopaminergic neurons by scavenging ROS and inhibiting α-synuclein aggregation, suggesting potential in Parkinson’s disease therapy.

Despite their promise, challenges remain in optimizing nanozyme design for clinical translation. Particle size, surface charge, and coating influence biodistribution and catalytic activity. Polyethylene glycol (PEG) coatings improve circulation time, while targeting moieties like peptides enhance tissue specificity. Long-term safety studies are necessary to evaluate potential accumulation and immune responses. Additionally, the dynamic ROS scavenging behavior of nanozymes requires precise tuning to avoid disrupting redox signaling essential for normal cellular functions.

In summary, nanozymes such as CeO2 and Pt NPs offer a versatile platform for enhancing tissue repair in ischemic and aged models through their ROS-scavenging capabilities. Their catalytic mechanisms, dosing strategies, and regenerative applications underscore their potential as next-generation therapeutics in regenerative medicine. Future research should focus on scalable synthesis, targeted delivery systems, and clinical validation to fully realize their therapeutic impact.