Infection-driven proliferative phase impairment in chronic wounds: a mechanistic framework for precision regenerative...

Area of Science:

• Regenerative Medicine
• Microbiology
• Wound Healing Biology

Background:

• Chronic wounds exhibit persistent tissue repair failure beyond infection and inflammation.
• Microbial communities in chronic wounds create pathogenic ecosystems that impair healing.
• The proliferative phase is critical for wound repair, involving cell growth, blood vessel formation, and tissue reconstruction.

Purpose of the Study:

• Introduce the conceptual framework of infection-driven proliferative phase impairment (IDPPI).
• Explain how microbial activities disrupt the host's regenerative programs during wound healing.
• Propose a novel therapeutic paradigm for chronic wound management.

Main Methods:

• Synthesize current evidence on microbial virulence, biofilm formation, and host immune-metabolic dysregulation.
• Analyze mechanisms of proliferative arrest, including cellular injury and signaling pathway disruption.
• Outline a multi-level therapeutic strategy focusing on microbial disarmament and regenerative promotion.

Main Results:

• IDPPI describes a pathological state where microbial actions continuously compromise host repair.
• Coordinated microbial virulence, biofilms, and immune-metabolic issues lead to stalled wound regeneration.
• A targeted therapeutic approach involves suppressing virulence/biofilms, restoring homeostasis, and promoting regeneration.

Conclusions:

• IDPPI provides an integrative framework for understanding chronic wound failure.
• Therapeutic strategies should focus on functional microbial disarmament and enhancing host repair capacity.
• Future advancements in multi-omics, AI, and sensing will enable adaptive, closed-loop regenerative medicine for chronic wounds.