{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:25:31Z","timestamp":1793384731603,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Skin tissue repair is of fundamental importance for maintaining homeostasis regulation, protection barrier, absorption, and excretion of skin tissue. Wound healing is a complicated process that can be impaired by infections and therefore have a significant economic and social impact. Simultaneously, the overuse of antibiotics has led to antimicrobial resistance and loss of their efficacy. Thus, the need for alternative antimicrobial agents is urgent. The newest approaches on wound dressings employ new therapeutic agents, such as probiotics. Probiotics alone or in tandem with nanotechnology-based techniques exhibit a broad range of benefits on surgical wounds. This systematic review aims to consider current knowledge of probiotic effects on animals and humans regarding surgical wound healing and provide new insights into the role of nanotechnology. The databases included were PubMed (MEDLINE), Scopus, and Cochrane Library (CENTRAL). Studies focused on burns, chronic wounds, and diabetic ulcers were excluded. The promising industry of probiotics demonstrates a significant upsurge as more and more healthy individuals rely their well-being on alternative medicine. Included probiotics illustrated positive results on wound re-epithelization, neovascularization, and wound healing. No adverse effects were noted.<\/jats:p>","DOI":"10.3390\/nu13124265","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:56Z","timestamp":1638314576000},"page":"4265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Probiotics and Their Effect on Surgical Wound Healing: A Systematic Review and New Insights into the Role of Nanotechnology"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1143-2293","authenticated-orcid":false,"given":"Alexandra","family":"Bekiaridou","sequence":"first","affiliation":[{"name":"1st Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7094-0338","authenticated-orcid":false,"given":"Eleni","family":"Karlafti","sequence":"additional","affiliation":[{"name":"1st Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3620-4462","authenticated-orcid":false,"given":"Ilias Marios","family":"Oikonomou","sequence":"additional","affiliation":[{"name":"1st Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristidis","family":"Ioannidis","sequence":"additional","affiliation":[{"name":"1st Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki (AUTH), 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7097-9889","authenticated-orcid":false,"given":"Theodossis S.","family":"Papavramidis","sequence":"additional","affiliation":[{"name":"1st Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki (AUTH), 54621 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.cnur.2017.04.008","article-title":"Impairments in Skin Integrity","volume":"52","author":"Murphree","year":"2017","journal-title":"Nurs. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mawalla, B., Mshana, S.E., Chalya, P.L., Imirzalioglu, C., and Mahalu, W. (2011). Predictors of surgical site infections among patients undergoing major surgery at Bugando Medical Centre in Northwestern Tanzania. BMC Surg., 11.","DOI":"10.1186\/1471-2482-11-21"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Szultka-M\u0142y\u0144ska, M., Janiszewska, D., Pomastowski, P., Z\u0142och, M., Kupczyk, W., and Buszewski, B. (2021). Identification of Bacteria Associated with Post-Operative Wounds of Patients with the Use of Matrix-Assisted Laser Desorption\/Ionization Time-of-Flight Mass Spectrometry Approach. Molecules, 26.","DOI":"10.3390\/molecules26165007"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/B978-1-4831-9711-1.50022-3","article-title":"The Antibiotics","volume":"11","author":"Abraham","year":"1963","journal-title":"Compr. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Poutahidis, T., Kearney, S.M., Levkovich, T., Qi, P., Varian, B.J., Lakritz, J., Ibrahim, Y.M., Chatzigiagkos, A., Alm, E.J., and Erdman, S.E. (2013). Microbial Symbionts Accelerate Wound Healing via the Neuropeptide Hormone Oxytocin. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078898"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e2658","DOI":"10.1097\/MD.0000000000002658","article-title":"Clinical Uses of Probiotics","volume":"95","author":"Islam","year":"2016","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40168-020-00866-1","article-title":"Skin microbiota analysis-inspired development of novel anti-infectives","volume":"8","author":"Liu","year":"2020","journal-title":"Microbiome"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1177\/039463200802100115","article-title":"Increase of Skin-Ceramide Levels in Aged Subjects following a Short-Term Topical Application of Bacterial Sphingomyelinase from Streptococcus Thermophilus","volume":"21","author":"Cinque","year":"2008","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1046\/j.1523-1747.1999.00633.x","article-title":"Effect of the Lactic Acid BacteriumStreptococcus thermophilus on Ceramide Levels in Human KeratinocytesIn Vitro and Stratum Corneum In Vivo","volume":"113","author":"Cinque","year":"1999","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1086\/340126","article-title":"Lactobacillus fermentumRC-14 InhibitsStaphylococcus aureusInfection of Surgical Implants in Rats","volume":"185","author":"Gan","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_11","first-page":"43","article-title":"Effect of Topical Kefir Application on Open Wound Healing: An In Vivo Study","volume":"9","author":"Atalan","year":"2003","journal-title":"Kafk \u00dcn\u00efvers\u00eftes\u00ef Veter\u00efner Fak\u00fcltesi Derg\u00efs\u00ef"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.ijantimicag.2004.09.020","article-title":"Antimicrobial and healing activity of kefir and kefiran extract","volume":"25","author":"Rodrigues","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1177\/153537020322801111","article-title":"Wound Healing and Angiogenic Properties of Supernatants from Lactobacillus Cultures","volume":"228","author":"Halper","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.5897\/AJMR11.956","article-title":"Comparison of the effects of Lactobacillus brevis and Lactobacillus plantarum on cutaneous wound healing in rats","volume":"5","author":"Zahedi","year":"2011","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4314\/ajcem.v18i1.1","article-title":"In vitro and in vivo antimicrobial activity of partially purified enterocin produced by Enterococcus faecalis and its application in wound healing","volume":"18","author":"David","year":"2016","journal-title":"Afr. J. Clin. Exp. Microbiol."},{"key":"ref_16","first-page":"2395","article-title":"Study of cutaneous wound healing in rats treated with Lactobacillus plantarum on days 1, 3, 7, 14 and 21","volume":"5","author":"Nasrabadi","year":"2011","journal-title":"Afr. J. Pharm. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/j.1742-481X.2011.00889.x","article-title":"Novel Nitric Oxide Producing Probiotic Wound Healing Patch: Preparation and in vivo Analysis in a New Zealand White Rabbit Model of Ischaemic and Infected Wounds","volume":"9","author":"Jones","year":"2012","journal-title":"Int. Wound J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3928","DOI":"10.1128\/AAC.00622-13","article-title":"Evaluation of a Nisin-Eluting Nanofiber Scaffold to Treat Staphylococcus aureus-Induced Skin Infections in Mice","volume":"57","author":"Heunis","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3948","DOI":"10.1128\/AAC.02938-15","article-title":"Efficacy of Lantibiotic Treatment of Staphylococcus aureus-Induced Skin Infections, Monitored by In Vivo Bioluminescent Imaging","volume":"60","author":"Staden","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.ijbiomac.2017.07.136","article-title":"Preparation and characterization of hydroxypropyl chitosan modified with nisin","volume":"105","author":"Zhu","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1097\/SCS.0000000000003469","article-title":"Antibacterial Effect of Bacteriocin Isolated from Lactobacillus Plantarum ATCC 8014 on Postoperative Infection of Mandibular Fracture In Vivo","volume":"28","author":"Fu","year":"2017","journal-title":"J. Craniofac. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8009","DOI":"10.12659\/MSM.909630","article-title":"Bacteriocin Isolated from Lactobacillus Rhamnosus L34 Has Antibacterial Effects in a Rabbit Model of Infection After Mandible Fracture Fixation","volume":"24","author":"Fu","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s12602-018-9505-9","article-title":"Lactobacillus plantarum USM8613 Aids in Wound Healing and Suppresses Staphylococcus aureus Infection at Wound Sites","volume":"12","author":"Ong","year":"2019","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"312","DOI":"10.12659\/MSM.912971","article-title":"The Combined Use of Tea Polyphenols and Lactobacillus Plantarum ST8SH Bacteriocin in a Rabbit Model of Infection Following Femoral Fracture with Internal Fixation","volume":"25","author":"Xu","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/wrr.12743","article-title":"Immunomodulatory potential of Nisin A with application in wound healing","volume":"27","author":"Mouritzen","year":"2019","journal-title":"Wound Repair Regen."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"335","DOI":"10.30802\/AALAS-CM-19-000102","article-title":"Evaluation of Topical Lysostaphin as a Novel Treatment for Instrumented Rhesus Macaques (Macaca mulatta) Infected with Methicillin- Resistant Staphylococcus aureus","volume":"70","author":"Diaz","year":"2020","journal-title":"Comp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.ijbiomac.2020.07.192","article-title":"Characterization and antibacterial action mode of bacteriocin BMP32r and its application as antimicrobial agent for the therapy of multidrug-resistant bacterial infection","volume":"164","author":"Qiao","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.00829-20","article-title":"Successful Development of Bacteriocins into Therapeutic Formulation for Treatment of MRSA Skin Infection in a Murine Model","volume":"64","author":"Ovchinnikov","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Nam, Y., Kim, J., Baek, J., and Kim, W. (2021). Improvement of Cutaneous Wound Healing via Topical Application of Heat-Killed Lactococcus chungangensis CAU 1447 on Diabetic Mice. Nutrients, 13.","DOI":"10.3390\/nu13082666"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"676534","DOI":"10.3389\/fimmu.2021.676534","article-title":"A Strong Synergy between the Thiopeptide Bacteriocin Micrococcin P1 and Rifampicin against MRSA in a Murine Skin Infection Model","volume":"12","author":"Ovchinnikov","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/j.peptides.2011.07.004","article-title":"Plantaricin A synthesized by Lactobacillus plantarum induces in vitro proliferation and migration of human keratinocytes and increases the expression of TGF-\u03b21, FGF7, VEGF-A and IL-8 genes","volume":"32","author":"Pinto","year":"2011","journal-title":"Peptides"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.ijbiomac.2014.08.041","article-title":"Synthesis of antimicrobial Nisin-phosphorylated soybean protein isolate\/poly(l-lactic acid)\/ZrO2 membranes","volume":"72","author":"Jiang","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s00284-015-0813-y","article-title":"Co-spinning of Silver Nanoparticles with Nisin Increases the Antimicrobial Spectrum of PDLLA: PEO Nanofibers","volume":"71","author":"Ahire","year":"2015","journal-title":"Curr. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33827","DOI":"10.1021\/acsami.8b08770","article-title":"Developing Antibacterial Nanocrystalline Cellulose Using Natural Antibacterial Agents","volume":"10","author":"Tavakolian","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Twomey, E., Hill, C., Field, D., and Begley, M. (2020). Bioengineered Nisin Derivative M17Q Has Enhanced Activity against Staphylococcus epidermidis. Antibiotibiotics, 9.","DOI":"10.3390\/antibiotics9060305"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.ijbiomac.2020.01.164","article-title":"Enhanced stability of the bactericidal activity of nisin through conjugation with gellan gum","volume":"148","author":"Peng","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"105333","DOI":"10.1016\/j.ejps.2020.105333","article-title":"Preformulation studies on novel garvicin KS peptides for topical applications","volume":"151","author":"Thapa","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0197-2456(95)00134-4","article-title":"Assessing the quality of reports of randomized clinical trials: Is blinding necessary?","volume":"17","author":"Jadad","year":"1996","journal-title":"Control. Clin. Trials"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/0022034509359125","article-title":"Factors Affecting Wound Healing","volume":"89","author":"Guo","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/01.ASW.0000617008.87552.bc","article-title":"Checklist for Successful Wound Healing Outcomes","volume":"33","author":"Hess","year":"2020","journal-title":"Adv. Ski. Wound Care"},{"key":"ref_41","first-page":"265","article-title":"The effect of Lactobacillus brevis isolated from Iranian traditional cheese on cutaneous wound healing in rats","volume":"5","author":"Zahedi","year":"2011","journal-title":"J. Cell Anim. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1097\/01.ASW.0000428952.00149.77","article-title":"The Effect of a Hydrocolloid Dressing Containing Ceramide-2 on Split-Thickness Wounds in a Laser-Induced Erosion Model","volume":"26","author":"Tsuchiya","year":"2013","journal-title":"Adv. Ski. Wound Care"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/s12602-010-9047-2","article-title":"A Comparative Study Between the Antibacterial Effect of Nisin and Nisin-Loaded Chitosan\/Alginate Nanoparticles on the Growth of Staphylococcus aureus in Raw and Pasteurized Milk Samples","volume":"2","author":"Zohri","year":"2010","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.3389\/fmicb.2016.01385","article-title":"Nanotechnology: A Valuable Strategy to Improve Bacteriocin Formulations","volume":"7","author":"Fahim","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S129","DOI":"10.1093\/cid\/civ085","article-title":"Risk and Safety of Probiotics","volume":"60","author":"Doron","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1517\/14740338.2014.872627","article-title":"A systematic review of the safety of probiotics","volume":"13","author":"Didari","year":"2013","journal-title":"Expert Opin. Drug Saf."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4265\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:36:28Z","timestamp":1760168188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,26]]},"references-count":46,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["nu13124265"],"URL":"https:\/\/doi.org\/10.3390\/nu13124265","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,26]]}}}