Nanocascade Engineering Workshop for Synergistic Microenvironment Reprogramming and EpSC Revitalization in Precise...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Wound Healing

Background:

• Chronic wounds, especially diabetic ones, exhibit impaired closure due to chronic inflammation and reduced stem cell function.
• The inflammatory microenvironment critically hinders epidermal stem cell (EpSC) proliferation and differentiation, delaying wound healing.
• Current treatments often face reduced efficacy in the pathological milieu of chronic wounds.

Purpose of the Study:

• To develop a nanotherapy that simultaneously modulates the inflammatory microenvironment and enhances EpSC function for accelerated chronic wound closure.
• To investigate the efficacy of a core-shell nanostructure in promoting regeneration and combating infection in chronic wound models.

Main Methods:

• Designed a core-shell nanostructure (Cu5.4O@LL-37/pDNA) comprising a Cu5.4O nanozyme core and an LL-37/pDNA shell.
• The Cu5.4O core scavenges reactive oxygen species and modulates the inflammatory milieu.
• The LL-37/pDNA shell enhances gene delivery and provides antibacterial properties.

Main Results:

• The nanotherapy effectively reshaped the inflammatory microenvironment, creating a regenerative niche.
• It promoted EpSC proliferation and differentiation by enhancing gene delivery and sustained P311 expression.
• Accelerated re-epithelialization and wound closure were observed in both diabetic and infection models.

Conclusions:

• The developed nanotherapy offers a dual-action approach to chronic wound management by addressing both the microenvironment and cellular dysfunction.
• This strategy shows significant potential for achieving durable and effective healing in challenging chronic wounds.
• The Cu5.4O@LL-37/pDNA system represents a novel therapeutic avenue for regenerative medicine in wound care.