The Impact of Nicotine on Wound Healing: A Comparative Review of Cigarettes, Vaping, and Nicotine Patches with Insights into Pathophysiological Mechanisms
Main Article Content
Abstract
Nicotine, a key component of tobacco products, significantly impacts wound healing through its effects on vascular response, inflammation, and cellular functions critical to tissue repair. The introduction of alternative nicotine delivery systems, such as e-cigarettes and transdermal patches, has raised questions about their relative safety compared to traditional cigarettes. This review explores the effects of nicotine delivery methods on wound healing, focusing on the mechanisms of nicotine-induced vasoconstriction, oxidative stress, angiogenesis, and immune modulation.
Cigarettes impair wound healing due to the combined effects of nicotine, carbon monoxide, and tar, which disrupt oxygen delivery, increase inflammation, and weaken collagen remodeling. E-cigarettes, while combustion-free, still hinder wound repair through nicotine's effects on keratinocyte migration and mitochondrial function. Nicotine patches, though safer than smoking, have complex effects depending on dose and duration. While preoperative smoking cessation significantly improves surgical outcomes, careful management of nicotine replacement therapies is critical to minimizing adverse effects. This review highlights the need for further research into the long-term impact of vaping and strategies to optimize nicotine cessation in surgical care.
Article Details
How to Cite
BONILLA, Juan C et al.
The Impact of Nicotine on Wound Healing: A Comparative Review of Cigarettes, Vaping, and Nicotine Patches with Insights into Pathophysiological Mechanisms.
Medical Research Archives, [S.l.], v. 13, n. 6, june 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6635>. Date accessed: 15 july 2025.
doi: https://doi.org/10.18103/mra.v13i6.6635.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Benowitz NL. Nicotine addiction. N Engl J Med. 2010;362(24):2295-2303. doi:10.1056/NEJMra080 9890
2. Price LR, Martinez J. Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: a narrative review of the scientific literature. F1000Res. 2019;8:1586. doi:10.12688/f1000research.20062.2
3. Walser T, Cui X, Yanagawa J, et al. Smoking and lung cancer: the role of inflammation. Proc Am Thorac Soc.2008;5(8):811-815. doi:10.1513/pats.2 00809-100TH
4. Zia S, Ndoye A, Lee TX, Webber RJ, Grando SA. Receptor-mediated inhibition of keratinocyte migration by nicotine involves modulations of calcium influx and intracellular concentration. J Pharmacol Exp Ther.2000;293(3):973-981.
5. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg. 2012;255(6):1069-1079. doi:10.1097/SLA.0b013e31824f632d
6. de Almeida TF, Romana-Souza B, Machado S, Abreu-Villaça Y, Monte-Alto-Costa A. Nicotine affects cutaneous wound healing in stressed mice. Exp Dermatol. 2013;22(8):524-529. doi:10.1111/exd.12186
7. Whitehead AK, Erwin AP, Yue X. Nicotine and vascular dysfunction. Acta Physiol (Oxf). 2021 Apr; 231(4):e13631. doi: 10.1111/apha.13631. Epub 2021 Feb 24. PMID: 33595878; PMCID: PMC8026694.
8. Xanthoulea S, Deliaert A, Romano A, et al. Nicotine effect on inflammatory and growth factor responses in murine cutaneous wound healing. Int Immunopharmacol. 2013;17(4):1155-1164.
doi:10.1016/j.intimp.2013.10.022
9. Jacobi J, Jang JJ, Sundram U, et al. Nicotine accelerates angiogenesis and wound healing in genetically diabetic mice. Am J Pathol. 2002;161 (1):97-104. doi:10.1016/S0002-9440(10)64161-2
10. Morimoto N, Takemoto S, Kawazoe T, Suzuki S. Nicotine at a low concentration promotes wound healing. J Surg Res. 2008;145(2):199-204. doi:10.1016/j.jss.2007.05.031
11. Martin JW, Mousa SS, Shaker O, Mousa SA. The multiple faces of nicotine and its implications in tissue and wound repair. Exp Dermatol. 2009; 18 (6):497-505. doi:10.1111/j.1600-0625.2009.00854.x
12. Silverstein P. Smoking and wound healing. Am J Med. 1992;93(1A):22S-24S. doi:10.1016/0002-9343(92)90623-j
13. Lei W, Lerner C, Sundar IK, Rahman I. Myofibroblast differentiation and its functional properties are inhibited by nicotine and e-cigarette via mitochondrial OXPHOS Complex III. Sci Rep. 2017;7:43213. doi:10.1038/srep43213
14. Kennedy P, Saloky K, Yadavalli A, et al. Nicotine exposure via electronic cigarettes significantly impedes biomechanical healing properties of tendon healing in a rat model. Arthroscopy. 2021; 37(10):3170-3176. doi:10.1016/j.arthro.2021.03.071
15. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg. 2012;255(6):1069-1079. doi:10.1097/SLA.0b013e31824f632d
16. Jin MF, Campbell EH, Somani AK. Is there a smoking gun for nicotine? A review of the role of nicotine in dermatologic surgery. Dermatol Surg. 2022;48(11):1171-1175. doi:10.1097/DSS.000000 0000003547
17. Sørensen LT, Toft BG, Rygaard J, et al. Effect of smoking, smoking cessation, and nicotine patch on wound dimension, vitamin C, and systemic markers of collagen metabolism. Surgery. 2010;148(5):982-990. doi:10.1016/j.surg.2010.02.005
18. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg. 2012;255(6):1069-1079. doi:10.1097/SLA.0b013e31824f632d
19. Rinker B. The evils of nicotine: an evidence-based guide to smoking and plastic surgery. Ann Plast Surg.2013;70(5):599-605. doi:10.1097/SAP.0 b013e3182764fcd
20. Silverstein P. Smoking and wound healing. Am J Med. 1992;93(1A):22S-24S. doi:10.1016/0002-9343(92)90623-j
21. Fan Chiang YH, Lee YW, Lam F, et al. Smoking increases the risk of postoperative wound complications: a propensity score-matched cohort study. Int Wound J. 2023;20(2):391-402. doi:10.11 11/iwj.13887
22. Jin MF, Campbell EH, Somani AK. Is there a smoking gun for nicotine? A review of the role of nicotine in dermatologic surgery. Dermatol Surg. 2022;48(11):1171-1175. doi:10.1097/DSS.000000 0000003547
23. Fiddes RA, McCaffrey N. Preoperative smoking-cessation interventions to prevent postoperative complications: a quality assessment and overview of systematic review evidence. Anesth Analg. 2024. doi:10.1213/ANE.0000000000007187
24. Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC expert consensus decision pathway on tobacco cessation treatment: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2018;72 (25):3332-3365. doi:10.1016/j.jacc.2018.10.027
25. Rinker B. The evils of nicotine: an evidence-based guide to smoking and plastic surgery. Ann Plast Surg.2013;70(5):599-605. doi:10.1097/SAP.0 b013e3182764fcd
26. Jin MF, Campbell EH, Somani AK. Is there a smoking gun for nicotine? A review of the role of nicotine in dermatologic surgery. Dermatol Surg. 2022;48(11):1171-1175. doi:10.1097/DSS.000000 0000003547
27. Yousefzadeh A, Chung F, Wong DT, Warner DO, Wong J. Smoking cessation: the role of the anesthesiologist. Anesth Analg. 2016;122(5):1311-1320. doi:10.1213/ANE.0000000000001170
28. National Center for Biotechnology Information. PubChem Compound Summary for CID 89594, Nicotine. PubChem website. https://pubchem.ncbi.nlm.nih.gov/compound/Nicotine.
29. Olsson Gisleskog PO, Perez Ruixo JJ, Westin Å, et al. Nicotine population pharmacokinetics in healthy smokers after intravenous, oral, buccal and transdermal administration. Clin Pharmacokinet. 2021;60:541-561. doi:10.1007/s40262-020-00960-5
30. Benowitz NL, Hukkanen J, Jacob P III. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol. 2009;(192):29-60. doi:10.1007/978-3-540-69248-5_2
31. Gupta SK, Benowitz NL, Jacob P, Rolf CN, Gorsline J. Bioavailability and absorption kinetics of nicotine following application of a transdermal system. Br J Clin Pharmacol. 1993;36:221-227.
32. American Society of Health-System Pharmacists. AHFS Drug Information 2009. Bethesda, MD; 2009.
33. Martin JW, Mousa SS, Shaker O, Mousa SA. The multiple faces of nicotine and its implications in tissue and wound repair. Exp Dermatol. 2009;18 (6):497-505. doi:10.1111/j.1600-0625.2009.00854.x
34. Yingst JM, Foulds J, Veldheer S, et al. Nicotine absorption during electronic cigarette use among regular users. PLoS One. 2019;14(7):e0220300. doi:10.1371/journal.pone.0220300
35. Schroeder MJ, Hoffman AC. Electronic cigarettes and nicotine clinical pharmacology. Tob Control. 2014;23(Suppl 2):ii30–ii35. doi:10.1136/to baccocontrol-2013-051469
36. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg. 2012;255(6):1069-1079. doi:10.1097/SLA.0b013e31824f632d
37. Abtahi Froushani SM, Ajami M, Mahmoudzadeh M. Effect of nicotine on immune system function. Adv Pharm Bull. 2022. doi:10.34172/apb.2022.032
38. Cardinale A, Nastrucci C, Cesario A, Russo P. Nicotine: specific role in angiogenesis, proliferation and apoptosis. Crit Rev Toxicol. 2012;42(1):68-89. doi:10.3109/10408444.2011.623150
39. Cooke JP. Angiogenesis and the role of the endothelial nicotinic acetylcholine receptor. Life Sci. 2007;80(24-25):2347-2351. doi:10.1016/j.lfs.2 007.01.061
40. Heeschen C, Weis M, Aicher A, Dimmeler S, Cooke JP. A novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine receptors. J Clin Invest. 2002;110(4):527-536. doi:10.1172/JC I14676
41. Silverstein P. Smoking and wound healing. Am J Med. 1992;93(1A):22S-24S. doi:10.1016/0002-9343(92)90623-j
42. Knuutinen A, Kokkonen N, Risteli J, et al. Smoking affects collagen synthesis and extracellular matrix turnover in human skin. Br J Dermatol. 2002;146(4):588-594. doi:10.1046/j.1365-2133.20 02.04694.x
43. Misery L. Nicotine effects on skin: are they positive or negative? Exp Dermatol. 2004;13(11): 665-670. doi:10.1111/j.0906-6705.2004.00274.x
2. Price LR, Martinez J. Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: a narrative review of the scientific literature. F1000Res. 2019;8:1586. doi:10.12688/f1000research.20062.2
3. Walser T, Cui X, Yanagawa J, et al. Smoking and lung cancer: the role of inflammation. Proc Am Thorac Soc.2008;5(8):811-815. doi:10.1513/pats.2 00809-100TH
4. Zia S, Ndoye A, Lee TX, Webber RJ, Grando SA. Receptor-mediated inhibition of keratinocyte migration by nicotine involves modulations of calcium influx and intracellular concentration. J Pharmacol Exp Ther.2000;293(3):973-981.
5. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg. 2012;255(6):1069-1079. doi:10.1097/SLA.0b013e31824f632d
6. de Almeida TF, Romana-Souza B, Machado S, Abreu-Villaça Y, Monte-Alto-Costa A. Nicotine affects cutaneous wound healing in stressed mice. Exp Dermatol. 2013;22(8):524-529. doi:10.1111/exd.12186
7. Whitehead AK, Erwin AP, Yue X. Nicotine and vascular dysfunction. Acta Physiol (Oxf). 2021 Apr; 231(4):e13631. doi: 10.1111/apha.13631. Epub 2021 Feb 24. PMID: 33595878; PMCID: PMC8026694.
8. Xanthoulea S, Deliaert A, Romano A, et al. Nicotine effect on inflammatory and growth factor responses in murine cutaneous wound healing. Int Immunopharmacol. 2013;17(4):1155-1164.
doi:10.1016/j.intimp.2013.10.022
9. Jacobi J, Jang JJ, Sundram U, et al. Nicotine accelerates angiogenesis and wound healing in genetically diabetic mice. Am J Pathol. 2002;161 (1):97-104. doi:10.1016/S0002-9440(10)64161-2
10. Morimoto N, Takemoto S, Kawazoe T, Suzuki S. Nicotine at a low concentration promotes wound healing. J Surg Res. 2008;145(2):199-204. doi:10.1016/j.jss.2007.05.031
11. Martin JW, Mousa SS, Shaker O, Mousa SA. The multiple faces of nicotine and its implications in tissue and wound repair. Exp Dermatol. 2009; 18 (6):497-505. doi:10.1111/j.1600-0625.2009.00854.x
12. Silverstein P. Smoking and wound healing. Am J Med. 1992;93(1A):22S-24S. doi:10.1016/0002-9343(92)90623-j
13. Lei W, Lerner C, Sundar IK, Rahman I. Myofibroblast differentiation and its functional properties are inhibited by nicotine and e-cigarette via mitochondrial OXPHOS Complex III. Sci Rep. 2017;7:43213. doi:10.1038/srep43213
14. Kennedy P, Saloky K, Yadavalli A, et al. Nicotine exposure via electronic cigarettes significantly impedes biomechanical healing properties of tendon healing in a rat model. Arthroscopy. 2021; 37(10):3170-3176. doi:10.1016/j.arthro.2021.03.071
15. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg. 2012;255(6):1069-1079. doi:10.1097/SLA.0b013e31824f632d
16. Jin MF, Campbell EH, Somani AK. Is there a smoking gun for nicotine? A review of the role of nicotine in dermatologic surgery. Dermatol Surg. 2022;48(11):1171-1175. doi:10.1097/DSS.000000 0000003547
17. Sørensen LT, Toft BG, Rygaard J, et al. Effect of smoking, smoking cessation, and nicotine patch on wound dimension, vitamin C, and systemic markers of collagen metabolism. Surgery. 2010;148(5):982-990. doi:10.1016/j.surg.2010.02.005
18. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg. 2012;255(6):1069-1079. doi:10.1097/SLA.0b013e31824f632d
19. Rinker B. The evils of nicotine: an evidence-based guide to smoking and plastic surgery. Ann Plast Surg.2013;70(5):599-605. doi:10.1097/SAP.0 b013e3182764fcd
20. Silverstein P. Smoking and wound healing. Am J Med. 1992;93(1A):22S-24S. doi:10.1016/0002-9343(92)90623-j
21. Fan Chiang YH, Lee YW, Lam F, et al. Smoking increases the risk of postoperative wound complications: a propensity score-matched cohort study. Int Wound J. 2023;20(2):391-402. doi:10.11 11/iwj.13887
22. Jin MF, Campbell EH, Somani AK. Is there a smoking gun for nicotine? A review of the role of nicotine in dermatologic surgery. Dermatol Surg. 2022;48(11):1171-1175. doi:10.1097/DSS.000000 0000003547
23. Fiddes RA, McCaffrey N. Preoperative smoking-cessation interventions to prevent postoperative complications: a quality assessment and overview of systematic review evidence. Anesth Analg. 2024. doi:10.1213/ANE.0000000000007187
24. Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC expert consensus decision pathway on tobacco cessation treatment: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2018;72 (25):3332-3365. doi:10.1016/j.jacc.2018.10.027
25. Rinker B. The evils of nicotine: an evidence-based guide to smoking and plastic surgery. Ann Plast Surg.2013;70(5):599-605. doi:10.1097/SAP.0 b013e3182764fcd
26. Jin MF, Campbell EH, Somani AK. Is there a smoking gun for nicotine? A review of the role of nicotine in dermatologic surgery. Dermatol Surg. 2022;48(11):1171-1175. doi:10.1097/DSS.000000 0000003547
27. Yousefzadeh A, Chung F, Wong DT, Warner DO, Wong J. Smoking cessation: the role of the anesthesiologist. Anesth Analg. 2016;122(5):1311-1320. doi:10.1213/ANE.0000000000001170
28. National Center for Biotechnology Information. PubChem Compound Summary for CID 89594, Nicotine. PubChem website. https://pubchem.ncbi.nlm.nih.gov/compound/Nicotine.
29. Olsson Gisleskog PO, Perez Ruixo JJ, Westin Å, et al. Nicotine population pharmacokinetics in healthy smokers after intravenous, oral, buccal and transdermal administration. Clin Pharmacokinet. 2021;60:541-561. doi:10.1007/s40262-020-00960-5
30. Benowitz NL, Hukkanen J, Jacob P III. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol. 2009;(192):29-60. doi:10.1007/978-3-540-69248-5_2
31. Gupta SK, Benowitz NL, Jacob P, Rolf CN, Gorsline J. Bioavailability and absorption kinetics of nicotine following application of a transdermal system. Br J Clin Pharmacol. 1993;36:221-227.
32. American Society of Health-System Pharmacists. AHFS Drug Information 2009. Bethesda, MD; 2009.
33. Martin JW, Mousa SS, Shaker O, Mousa SA. The multiple faces of nicotine and its implications in tissue and wound repair. Exp Dermatol. 2009;18 (6):497-505. doi:10.1111/j.1600-0625.2009.00854.x
34. Yingst JM, Foulds J, Veldheer S, et al. Nicotine absorption during electronic cigarette use among regular users. PLoS One. 2019;14(7):e0220300. doi:10.1371/journal.pone.0220300
35. Schroeder MJ, Hoffman AC. Electronic cigarettes and nicotine clinical pharmacology. Tob Control. 2014;23(Suppl 2):ii30–ii35. doi:10.1136/to baccocontrol-2013-051469
36. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg. 2012;255(6):1069-1079. doi:10.1097/SLA.0b013e31824f632d
37. Abtahi Froushani SM, Ajami M, Mahmoudzadeh M. Effect of nicotine on immune system function. Adv Pharm Bull. 2022. doi:10.34172/apb.2022.032
38. Cardinale A, Nastrucci C, Cesario A, Russo P. Nicotine: specific role in angiogenesis, proliferation and apoptosis. Crit Rev Toxicol. 2012;42(1):68-89. doi:10.3109/10408444.2011.623150
39. Cooke JP. Angiogenesis and the role of the endothelial nicotinic acetylcholine receptor. Life Sci. 2007;80(24-25):2347-2351. doi:10.1016/j.lfs.2 007.01.061
40. Heeschen C, Weis M, Aicher A, Dimmeler S, Cooke JP. A novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine receptors. J Clin Invest. 2002;110(4):527-536. doi:10.1172/JC I14676
41. Silverstein P. Smoking and wound healing. Am J Med. 1992;93(1A):22S-24S. doi:10.1016/0002-9343(92)90623-j
42. Knuutinen A, Kokkonen N, Risteli J, et al. Smoking affects collagen synthesis and extracellular matrix turnover in human skin. Br J Dermatol. 2002;146(4):588-594. doi:10.1046/j.1365-2133.20 02.04694.x
43. Misery L. Nicotine effects on skin: are they positive or negative? Exp Dermatol. 2004;13(11): 665-670. doi:10.1111/j.0906-6705.2004.00274.x