Regenerative treatment of zinc-based nanoenzyme incorporated injectable hydrogel with mesenchymal stem cells alleviates spinal cord injury

Mesenchymal stem cells (MSCs)-derived therapy has surfaced as a viable approach for addressing spinal cord injury (SCI). The unfavorable milieu of SCI significantly impairs the paracrine and survival function of implanted MSCs, hence greatly restricting the therapeutic efficacy of this method. We present a zinc-based nanoenzyme (ZnNZs)-combined in situ forming thermoresponsive hydrogels (ZnNZ-HGL) that facilitate dual improvement of MSCs paracrine and viability effects, resulting in highly effective spinal cord reconstruction. The sol-gel transitions characteristic of ZnNZ-HGL at the physiological milieu guarantees consistent distribution of HGL in damaged spinal cord tissue. Our findings indicate that ZnNZ-HGL markedly enhances the survivability of MSCs within the milieu by mitigating oxidative stress (OS) and, crucially, stimulates the release of MSCs’ angiogenic factors. The interplay among the oxidative stress-mitigating properties of ZnNZs influence of MSC enhances nerve healing, angiogenesis, and functional recovery following SCI, presenting a promising approach for MSCs-derived SCI treatment.