Nicotine hinders healing for chronic wounds, complicating patient recovery.

• Identified 160 targets linking nicotine to chronic wound failure.
• Core inflammatory factors like TNF and IL-6 disrupted healing pathways.

Surgeons should consider nicotine’s role when assessing wound recovery potential in smokers.

• Strong binding affinity of nicotine to key targets TNF (-5.6 kcal/mol) and IL-6 (-5.0 kcal/mol) was confirmed.