Table 1.

Detailed summary of human and animal studies included. All the outcomes noted are significantly different from the control groups applied in every study.

Study	Year	Country	Target Area	Treatment	Probiotics Studied	Summary of Key Findings	Animal/ Human Study	Control
DiMarzio [8]	1999	Italy	Forearm skin	Base cream as vehicle containing S. thermophilus	S. thermophilus extracts	Significantly increased skin stratum corneum ceramide levels	Human	Base cream
DiMarzio [9]	2008	Italy	Forearm skin	Base cream as vehicle containing S. thermophilus	S. thermophilus extracts	Increased skin ceramides Significantly higher hydration values were found Improved the lipid barrier	Human	Base cream
Gan [10]	2002	Canada	Surgical implants	Solutions with biosurfactant from Lactobacillus	L. fermentum RC-14	Significantly inhibited S. aureus infection Inhibited bacteria adherence to surgical implants	Animal	Negative control group treated with PBS only
Atalan [11]	2003	Turkey	Wounds	Mixture of vaseline and kefir	Kefir	Enhanced wound healing	Animal	Mixture with vaseline
Rodriguez [12]	2005	Brasil	Wounds	Kefir gel	Kefir with Leuconostoc spp.; L. lactis, Acetobacter spp., Saccharomyces cerevisae, Kluyveromyces marxianus, and K. lactis	Enhanced wound healing measured by size and histology Improved granulation and neovascularization	Animal	Negative control group treated with 0.9% NaCl Positive control group treated with 5 mg/kg of neomycin–clostebol
Halper [13]	2008	Georgia	Wounds	Subcutaneous injection of lyophilized Lactobacillus supernatant	Lactobacilli	Stimulated inflammatory stage of tissue repair, TNF-a production, and angiogenesis	Animal	Group treated phosphate- buffered saline in 2% methylcellulose
Zahedi [14]	2011	Iran	Wounds	Ointment with 1010–1011 CFU/mL bacteria and eucerin	L. brevis L. plantarum	Significant reduction in inflammation Acceleration of wound healing in wounds treated with Lactobacilli	Animal	Untreated negative control group Group treated with eucerin
Zahedi [14]	2011	Iran	Wounds	Ointment with 1010–1011 CFU/mL bacteria and eucerin	L. brevis	Increased number of myofibroblasts Faster decreased inflammation cells Accelerated wound healing	Animal	Untreated negative control group
David [15]	2011	Nigeria	Surgical skin lesion	Gauze soaked in partially purified enterocin E3	Enterocin E3 from Enterococcus faecalis	Enterocin E3 was effective against S. aureus, Klebsiella pneumoniae, Enterobacter cloaca, Listeria monocytogenes, and Proteus vulgaris	Animal	Group treated with distilled water
Nasrabadi [16]	2011	Iran	Full-thickness wound	Mixture of Lactobacillus culture with eucerin	L. plantarum	Significant reduction in neutrophils, macrophages, and fibroblasts Significant decrease in inflammation Acceleration of re-epithelialization and re-vascularization	Animal	Positive control treated with eucerin Negative control group left untreated
Jones [17]	2012	Canada	Infected wounds	gNO dressings with microbeads containing L. fermentum 7230 and sodium nitrite (30 mM)	L. fermentum	Increased wound closure Histologically improved healing	Animal	Control patches with glucose (10% w/v), NaCl (0·85% w/v) and no sodium nitrite
Heunis [18]	2013	South Africa	Infected wounds	Antimicrobial nanofiber wound dressing	Nisin	Maintained its antistreptococcal activity in vitro for at least 4 days Remained active, even after storage of the formulation at 4 °C for 8 months Significantly reduced the colonization of S. aureus in a murine excisional skin infection model Induced an almost complete wound repair	Animal	Nanofiber wound dressings without nisin
Van Staden [19]	2016	South Africa	Infected wounds	Treatment with 12.5 μL (250 μM) of Amyloliquecidin, clausin, or nisin applied directly onto the wound	Nisin from L. lactis, Clausin, Amyloliquecidin	Significantly reduced the bioluminescence of S. aureus to a level similar to mupirocin treatment Reduced the bacterial load Enhanced wound closure and epithelialization	Animal	Mupirocin-based ointment
Zhu [20]	2017	China	Two strains of bacteria (S. aureus, and Bacillus subtilis)	Mixture with 50 mL sodium acetate buffer solution, 1.0 g hydroxypropyl chitosan, 1.1 g nisin, 0.25 g of Microbial transglutaminase powder	Nisin	Antibacterial activity against S. aureus Antibacterial properties against gram-positive bacteria Improved moisture absorption Promoted cell growth Good antioxidant activity	Animal	Hydroxypropyl chitosan blank control sample
Fu [21]	2017	China	Mandibular Fracture	Injection containing bacteriocin	Bacteriocin isolated from L. plantarum ATCC 8014	Bacteriocin could significantly reduce the formation of biofilms and inflammation factor	Animal	Group injected with 1 mL sterile saline solution
Fu [22]	2018	China	Mandibular fracture	Injection containing bacteriocin	Bacteriocin from L. rhamnosus L34	Serum levels of TNF-a and CRP were significantly lower than in controls Significantly reduced the formation of biofilms and inflammation of mandible fractures after internal fixation	Animal	Group injected with 1 mL sterile saline solution
Ong [23]	2019	Malaysia	Full thickness wound	A 10% (v/w) formulated ointment containing 50 μL of the protein-rich fraction from L. plantarum USM8613 with 500 mg of soft yellow paraffin	L. plantarum	Inhibited S. aureus growth Enhanced cytokines and chemokines, wound contraction, keratinocyte migration	Animal	Placebo-treated control group
Xu [24]	2019	China	Infected femoral Fracture with Internal Fixation	Injection with tea polyphenols and bacteriocins	Bacteriocin from L. plantarum ST8SH	Effectively controlled S. aureus infection	Animal	Negative control treated with saline
Mouritzen [25]	2019	Denmark	Wounds	Mixture of 25 μg/mL Nisin A, 100 ng/mL LPS, or a combination of Nisin A and LPS and incubated at 37 °C, 5% CO2	Nisin A from L. lactis and lipopolysaccharide	Dampened the effect of lipopolysaccharide and proinflammatory cytokines	Animal	Positive control were cells treated with free amino acids in the same mole-ratio as in Nisin A Negative control left untreated
Liu [7]	2020	China	S. aureus infected wound	PEG-PCL-MP1 formula	MP1 from S. hominis S34-1	Reduced S. aureus local and systemic infection	Animal	Negative control group MRSA- infected/PEG-PCL
Cheleuitte-Nieves [26]	2020	France	Infected cranial implant margins with MRSA	Liquid lysostaphin (5 mg/mL; total 3 mL/dose) applied topically	Bacteriocin lysostaphin	Decrease MRSA infection short-term, with no resistance discovered	Animal	Systemic administration of antibiotics
Qiao [27]	2020	China	Wounds	Treatment with PBS, 1 × MIC BMP32r (27.6 mg/L) Or 2 × MIC BMP32r (55.2 mg/L)	BMP32r from E. coli	Promoted wound healing by killing the multidrug-resistant S. aureus	Animal	Negative control group left untreated
Ovchinnikov [28]	2020	Norway	Wounds	Mixture containing 5 mg/mL garvicin KS, 5 mg/mL Penicillin G, and 0.1 mg/mL MP1 in 5% hydroxypropyl cellulose	Bacteriocin garvicin KS and MP1	Efficient in eradicating the MRSA from treated wounds Effective against gram-positive pathogens, such as coagulase-negative staphylococci and E. faecalis	Animal	Group treated with Fucidin cream
Nam [29]	2021	Korea	Wounds	100 µL of heat-killed Lc. chungangensis CAU 1447 combined with a eucerin ointment	L. chungangensis CAU 1447	Beneficial effects on wound healing	Animal	Negative control group left untreated Positive control group treated with 100 µL PBS)/wound area/day
Ovchinnikov [30]	2021	Norway	Wounds	MP1 (10 µg/mL) in base cream	MP1	Synergistic effects against MRSA Efficiently removed the pathogen from infection sites Prevented its recurrence and resistance development	Animal	Negative control left untreated Positive control treated with fucidin cream

Abbreviations: Enterocin E3, Enterococcus faecalis E3; L. Lactis, Lactobacillus Lactis; L. Brevis, Lactobacillus brevis; L. Plantarum, Lactobacillus plantarum; L. fermentum, Lactobacillus fermentum; L. Rhamnosus, Lactobacillus rhamnosus; MP1, Τhiopeptide bacteriocin micrococcin P1; PBS, phosphate-buffered saline; BMP32r, Bacteriocin BMP32r; E. coli, Escherichia coli; MRSA, Persistent methicillin-resistant S. aureus; PEG-PCL, glycol and polycaprolactone; Lc. Chungangensis, Lactococcus chungangensis.