Customized Proteinaceous Nanoformulation for In Vivo Chemical Reprogramming

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Tissue Engineering

Background:

• Sweat gland (SwG) regeneration is vital for burn patient recovery.
• In vivo chemical reprogramming offers endogenous organ regeneration but faces efficiency and environmental challenges.

Purpose of the Study:

• To develop a delivery system for efficient in vivo chemical reprogramming of epidermal cells into functional SwGs.
• To overcome limitations in current in vivo reprogramming strategies.

Main Methods:

• A functionalized proteinaceous nanoformulation was engineered to deliver seven SwG reprogramming components.
• The system targeted the dermal site for on-demand delivery of reprogramming agents.
• Epidermal keratinocytes were reprogrammed into SwG myoepithelial cells.

Main Results:

• Achieved the first successful in vivo chemical reprogramming of SwGs with 30.6% efficiency.
• Demonstrated efficient conversion of keratinocytes into SwG myoepithelial cells.
• The nanoformulation facilitated targeted delivery of multiple reprogramming agents.

Conclusions:

• The developed proteinaceous nanoformulation enables coordinated delivery for in vivo SwG reprogramming.
• This represents a non-surgical, non-viral, and cell-free strategy for in situ SwG regeneration.
• The approach significantly enhances clinical accessibility for regenerative therapies.