Honey- and Propolis-Based Agents in Dental Implantology: A Systematic Review of Antibacterial, Healing, and Osseointegration Effects

Abstract

Honey and propolis, recognized for their antimicrobial, antioxidant, and wound-healing properties, have gained attention as potential adjuncts in dental implantology. This systematic review aimed to assess and summarize existing evidence regarding the antibacterial, healing, and osseointegration effects of honey- and propolis-based agents when used in dental implant therapy, and to evaluate their impact on implant success and survival. A systematic search was conducted in accordance with the PRISMA guidelines across the PubMed, Scopus, Web of Science and Google Scholar databases up to June 2025. Eligible studies included clinical trials, animal experiments, and in vitro investigations that utilized honey or propolis in procedures related to dental implants. Assessed outcomes encompassed implant success, antimicrobial activity, osseointegration, tissue healing, and biocompatibility. Risk of bias was evaluated using appropriate assessment tools, and the results were synthesized descriptively. Fifteen studies were included (3 clinical, 6 animal, and 6 in vitro studies). Honey and propolis demonstrated strong antibacterial activity against Staphylococcus aureus and Staphylococcus mutans, supported bone healing, reduced oxidative stress, and exhibited biocompatibility. Honey-based surface coatings enhanced antibacterial effects and osteogenic responses. Clinical studies have reported improvements in peri-implant parameters with propolis gels and toothpaste; however, the evidence remains limited, and most studies carried a moderate risk of bias. Overall, these agents exhibit promising antibacterial, healing, and osseointegration effects in preclinical research; however, their impact on dental implant outcomes remains uncertain, necessitating more robust clinical trials.

Keywords

honey - propolis - dental implants - osseointegration - implant success

Introduction

Various surface treatments have been developed to enhance the osseointegration and long-term success of dental implants by optimizing surface roughness, improving antibacterial activity, and modulating inflammatory responses. Techniques such as sandblasting, laser etching, anodization, and the incorporation of silver nanoparticles create micro- and nano-scale surface features that increase implant stability and bone–implant contact.[1] [2] [3] Despite these advancements, no single modification can provide all the desirable characteristics needed, such as reliable osseointegration, effective infection control, soft-tissue compatibility, and predictable healing. Consequently, peri-implant complications, including poor stability, infection, osseointegration loss, dehiscence, and bone resorption, remain important concerns for both patients and clinicians.[4] [5] [6] [7]

To achieve an ideal implant surface with enhanced biocompatibility properties, trials were conducted using biological compounds such as honey, propolis, and bee products, which have demonstrated promising outcomes across multiple recent studies. One study investigated the effect of propolis toothpaste on oral microflora in individuals with dental implants, demonstrating improvements in plaque reduction and gingivitis.[8] Another study examined a novel implant coating incorporating propolis-derived flavonoid nanoaggregates to enhance osseointegration in rabbits, showing improved bone adhesion and reduced inflammation compared with controls.[9] An additional study synthesized honey-based silver nanoparticles for use in dental implants, demonstrating antibacterial activity against common oral pathogens.[10] Propolis's ability to inhibit Candida biofilm formation on titanium surfaces suggested its potential as a peri-implantitis treatment[11] and had a positive influence on antioxidant enzyme levels, reducing lipid peroxidation and oxidative stress in rabbits undergoing implant surgery.

Synthetic materials such as hydroxyapatite have been extensively studied and proven effective in enhancing osseointegration.[12] Natural substances, such as propolis and honey, present promising alternatives or adjuncts due to their inherent bioactive antibacterial and anti-inflammatory properties, which reduce the risk of infection and promote a favorable environment for bone healing.[13] [14]

There are several reviews; however, one review concentrated exclusively on propolis, failing to compare its findings with those associated with conventional agents, and offered only a superficial analysis of implant success and survival.[15] Other reviews were predominantly broad or narrative in nature, focusing on natural disinfectants or general oral health conditions rather than specifically addressing implant-related outcomes concerning antibacterial efficacy, healing, or osseointegration. Furthermore, none of these reviews undertook a systematic evaluation of implant success, survival, or potential biases.[16] [17] [18] [19] Therefore, the purpose of the present review was to systematically evaluate the evidence on honey- and propolis-based agents in dental implant therapy, focusing on their biocompatibility, antibacterial activity, anti-inflammatory effects, and ability to enhance soft-tissue and bone healing, and how these factors contribute to osseointegration, implant performance, and patient outcomes across clinical, animal, and in vitro studies.

Methods

Protocol and Registration

This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines[20] and registered in PROSPERO (CRD420251036271). The study objective was to identify, appraise, and summarize the available evidence on the applications and outcomes of honey-based products in relation to dental implant success and survival.

Research Question

A PICO search strategy was used to formulate the review question:

Population (P): Human patients receiving dental implants, in vivo animal models simulating implant procedures, and in vitro models of implant-related conditions; intervention (I): application of honey or honey-derived products (e.g., raw honey, propolis, honey-based nanoparticles, or coatings) during or after implant placement; comparison (C): placebo, untreated control, or other treatments such as chlorhexidine or saline; outcomes (O): dental implant success or survival, antibacterial activity, osseointegration, bone and soft tissue healing, and biocompatibility. “Implant survival” refers to the implant simply remaining in the mouth without being lost or removed, regardless of the condition of the surrounding tissues. In contrast, “implant success” uses stricter clinical criteria, typically including absence of pain, infection, mobility, peri-implant bone loss beyond accepted thresholds, and healthy soft-tissue conditions. Thus, survival measures whether the implant is still present, while success evaluates its overall functional and biological health.

The research question was “Do honey- and propolis-based agents enhance antibacterial activity, promote healing, and improve osseointegration and implant success compared with placebo or conventional treatments in clinical, animal, and in vitro models of dental implant therapy?”

Eligibility Criteria

Based on this systematic review focusing on the effects of honey and propolis in dental implantology, the following eligibility criteria were applied:

• Study design: Randomized clinical trials, in vivo animal studies, and in vitro experimental studies. However, reviews, commentaries, case reports, or non-original research were excluded.

• Type of intervention: Use of honey, propolis, or honey-derived formulations (e.g., nanoparticles, surface coatings) applied in the context of dental implant placement or peri-implant tissue healing.

• Control group requirements: Studies that compared the intervention to placebo, no treatment, or conventional therapies such as chlorhexidine.

• Clinical and experimental outcome measures: Implant success or survival, antibacterial activity, osseointegration, soft- and hard-tissue healing, oxidative stress response, and biocompatibility.

• Type of publication: Peer-reviewed articles published in English.

Information Sources and Search Strategy

A comprehensive web-based literature search was conducted to identify relevant studies. Databases searched included PubMed, Scopus, Web of Science, and Google Scholar covering literature up to June 2025. Keywords and combinations included the following: “honey,” “propolis,” “dental implants,” “osseointegration,” “antibacterial,” and “bioactive coatings.” Reference lists of included studies were also manually screened to identify any additional eligible records.

Study Selection

Search results were managed using Endnote 20.4.1, with duplicates removed prior to screening. Two independent reviewers screened titles and abstracts, followed by full-text assessments of potentially eligible studies. Discrepancies were resolved through discussion with a third reviewer. Additional studies were identified by manually searching databases and screening references of relevant articles to ensure comprehensive coverage.

Data Extraction

Data were extracted independently by two reviewers using a standardized data extraction form. Information collected included study type, sample size, study purpose, outcome measures, intervention type, comparators, and conclusions. Disagreements were resolved through discussion or consultation with a third reviewer.

Risk of Bias Assessment

The risk of bias for included studies was assessed using tools appropriate for each study type:

• Randomized clinical trials: The Cochrane ROB2 tool.[21]

• Animal studies: A modified version of the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist.[22] Each “yes” response received a score of 1, whereas “no” or “unclear” responses were assigned a score of 0. Based on total scores (out of 10), studies were categorized as high risk (0–3), medium risk (4–6), or low risk (7–10).

• In vitro studies: A modified version of the CONSORT checklist for reporting laboratory studies.

Two reviewers independently conducted the risk of bias assessments, with consensus achieved through discussion.

Data Synthesis

Due to the heterogeneity in study designs, interventions, and outcome measures, a meta-analysis was not feasible. Instead, a descriptive synthesis was performed. The included studies were categorized based on their primary focus, such as antimicrobial efficacy, osseointegration, biocompatibility, and clinical outcomes. Key findings were tabulated for comparative evaluation.

Results

Study Selection

The systematic review began with a web search that found 627 records. After excluding 413 duplicates, 214 unique records were screened, resulting in 197 rejections for not meeting the inclusion criteria. An additional record was found from the 17 records requested for full text, totaling 17. Ultimately, 15 records were included in the analysis,[2] [8] [9] [10] [11] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] while three were excluded for focusing on honey-based products unrelated to implant outcomes,[33] examined the antibacterial efficacy of Hubballi propolis but did not study prepared samples, such as in vitro implants,[34] and studied the antibacterial effectiveness of propolis on orthopedic screws, not dental implants.[35] This process is shown in [Fig. 1].

Fig. 1 PRISMA flow diagram illustrating the study selection process for the systematic review.

Risk of Bias Assessment

The risk of bias was evaluated using the ROB2 tool for clinical randomized trials, indicating that two studies displayed a low risk of bias,[26] [27] while one study showed a moderate risk of bias[8] ([Fig. 2]). Additionally, the CAMARADES tool evaluation for in vivo studies found that all six studies[2] [9] [11] [23] [31] [32] demonstrated a moderate risk of bias ([Table 1]). Furthermore, following the modified CONSORT checklist, all six studies[10] [24] [25] [28] [29] [30] demonstrated a moderate risk of bias ([Table 2]).

Table 1 Quality assessment of the included in vivo studies using the collaborative approach to meta-analysis and review of animal data from experimental studies (CAMARADES) tool (released in 2004)

CAMARADES tool	Aydin et al[23]	Somsanith et al[11]	Krasnikov et al[9]	Abdulla et al[2]	Abdulla et al[31]	Al-Molla et al[32]
1. Sample size calculation	0	0	0	0	0	0
2. Random allocation to treatment or control	0	0	0	1	1	0
3. Blinded implant/insertion of scaffold	0	0	0	0	0	0
4. Blinded assessment of outcome	0	0	0	0	0	0
5. Appropriate animal defect model	1	1	1	1	1	1
6. Administer anesthetics to the animal model as needed during the study	1	1	1	1	1	1
7. Statement of control of temperature	0	1	1	0	0	0
8. Compliance with animal welfare regulations	1	1	1	1	1	1
9. Peer-reviewed publication	1	1	1	1	1	1
10. Statement of potential conflict of interest	0	1	0	1	1	1
Score	4	6	5	6	6	5
Quality	Moderate risk	Moderate risk	Moderate risk	Moderate risk	Moderate risk	Moderate risk

Table 2 Quality assessment of the in vitro studies using the modified CONSORT tool for in vitro studies

Study	Abstract	Introduction		Methodology (intervention, outcomes, sample size, randomization, blinding, and statistical method)						Results	Discussion		“Funding has no influence” was reported	Total
Item	1	2a	2b	3	4	5	6	7	8	9	10	11	12
Kakaa et al[24]	Yes	Yes	Yes	Yes	Yes	No	No	No	Yes	Yes	Yes	No	Yes	9
Martorano-Fernandes et al[25]	Yes	Yes	No	Yes	Yes	No	No	No	Yes	Yes	Yes	No	Yes	8
Son et al[28]	Yes	Yes	No	Yes	Yes	No	No	No	Yes	Yes	Yes	No	Yes	8
SanaUllah et al[29]	Yes	Yes	No	Yes	Yes	No	No	No	Yes	Yes	Yes	No	Yes	8
Udduttula et al[30]	Yes	Yes	No	Yes	Yes	No	No	No	Yes	Yes	Yes	Yes	Yes	9
Zahid et al[10]	Yes	Yes	No	Yes	Yes	No	No	No	Yes	Yes	Yes	No	Yes	8

Fig. 2 Risk of bias assessment of included randomized controlled trials.

Characteristics of Included Studies

A total of 15 studies[2] [8] [9] [10] [11] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] were included in this review, comprising diverse experimental designs such as clinical randomized trials,[8] [26] [27] animal studies,[2] [9] [11] [23] [31] [32] and in vitro studies.[10] [24] [25] [28] [29] [30] The primary focus of the studies was the evaluation of propolis and other natural compounds as bioactive agents in dental implants and related applications.

Key interventions included propolis-containing toothpaste, propolis-loaded titanium nanotubes, honey-mediated zirconia, and hybrid coatings incorporating flavonoid nanoaggregates or silver nanoparticles. Comparators ranged from conventional treatments (e.g., chlorhexidine gels and standard titanium implants) to controls lacking active ingredients. Outcomes assessed varied widely and included oxidative stress markers, antibacterial activity, osseointegration metrics, and soft tissue healing. The characteristics of the included studies are shown in [Table 3].

Table 3 Characteristics of included studies

Study	Sample	Purpose of the study	Outcome measures	Intervention type of h P/concentration/mode of treatment	Comparator/s	Conclusion
Morawiec et al[8]; single-blind, two-group parallel clinical study	16 human patients	The study aimed to explore the impact of a propolis-containing hygiene agent on oral health parameters, oral microflora, and periodontal health in implant-supported prosthodontics	- Oral hygiene index (OHI, debris component) -API scores -Gingival bleeding -oral microbiota spectrum	Propolis-containing toothpaste (3%)	A negative control without an active ingredient (placebo toothpaste)	The study suggested that propolis-containing toothpaste could be a natural alternative to medicinal mouthwashes for periodontal problems caused by implants, but more research is needed to provide conclusive evidence.
Aydin et al[23]; in vivo	24 New Zealand white rabbits were divided into three groups	Evaluated the antioxidant effect of propolis on oxidative stress and bone repair after implant surgery	- Malondialdehyde levels - Antioxidant enzyme activity) - Vitamin D levels	- Local group Propolis solution (dissolved in dimethyl sulfoxide and diluted with saline) was applied to slots before placing the implants. - Systemic group Propolis solution was administered daily to rabbits by oral gavage after implantation	Control group Only the dental implant was placed in the prepared slot	Propolis diminishes oxidative stress and accelerates bone repair after implantation, particularly when used systemically
Somsanith et al[11]; in vitro and in vivo	- In vitro: MC3T3-E1 osteoblast-like cells. - In vivo: 20 male Sprague-Dawley rats were separated into two groups (10 each) to receive TNT or propolis-loaded TNT (PL-TNT-Ti) implants	The study evaluated the effect of TiO2 nanotubes (TNT) loaded with propolis on osseointegration and bone repair in dental implants	- Bone mineral density (xE—001 g/cm2) - New bone volume (mm3) -The microcomputed tomographic (µ-CT) analysis	Dental implants with propolis-loaded TNT (PL-TNT-Ti implants) TNT (TiO2 nanotubes) loaded with propolis (PL-TNT-Ti) dental implant	TNT implants without propolis	Propolis-loaded TNT implants improve osseointegration and bone regeneration while lowering inflammation. This modification to titanium dental implants shows potential for increasing implant durability and success rates
Kakaa et al[24]; in vitro	Pure titanium discs (1 cm2) and artificial saliva	The goal of this investigation was to determine how fluoride and propolis extract affected the corrosion behavior of commercially pure titanium (cp-Ti grade 2) in artificial saliva	Corrosion behavior of commercially pure titanium (cp-Ti grade 2) in artificial saliva	Propolis extract with different concentrations	Fluoride with different concentrations	Propolis in media elevated the metal's corrosion resistance
Martorano-Fernandes et al[25]; in vitro	Commercially pure titanium discs (1.3 × 0.2 cm) and artificial saliva	Brazilian red propolis was tested for its ability to suppress C. albicans (ATCC 90028) mono-species biofilms and co-culture biofilms of C. albicans (ATCC 90028) and C. glabrata (ATCC 2001) that were grown on titanium surfaces	Cell viability analysis: - Inhibition of biofilm formation. - Biofilm surface roughness	0.12% chlorhexidine and 3% red propolis extract	Sterile saline solution (growth control)	Brazilian red propolis has antifungal properties against Candida biofilms, making it a promising treatment for peri-implantitis
Priyadarshini et al[26]; randomized, controlled, pilot clinical study	20 participants, divided into two groups of 10 participants each	The study's goal was to examine the efficacy of two distinct oral therapeutic gels, Blue M gel (oxygen-enriched gel, sodium perborate, honey, and xylitol oxygen molecules [O2]) and hexigel (1% chlorhexidine gel), on soft tissue healing following dental implant for a period of 1 wk	Early wound healing index (EHS) after dental implant insertion	10 patients using Blue M gel (oxygen-enriched gel). The active ingredients such as sodium perborate, honey, and xylitol oxygen molecules (O2)	10 patients using Hexigel (1% chlorhexidine gel)	The study concluded that, while the oxygen-enriched blue M gel showed promise, chlorhexidine gel remains the gold standard for encouraging soft tissue healing after dental implant insertion, despite no statistically significant differences between the two groups
González-Serrano et al[27]; a randomized, double- blind study	Forty-six patients	To evaluate the efficiency of a gel containing propolis extract, nanovitamins C and E, as a complement to mechanical debridement for the management of the peri-implant region	The primary outcome is resolution of peri-implant mucositis (PM) with no bleeding on probing (BOP). Secondary outcomes: -Reduced clinical parameters: - Plaque index (PI). -Bleeding during probing (BOP) - Probing depth (PD) - Modified bleeding index (mBI). - Mucosal redness (MR) - The width of keratinized tissue (KT) - Reduced microbiological parameters: - Total bacterial count	Gel containing 2% propolis extract, 0.2% nanovitamin C, and 0.2% nanovitamin E	Placebo gel with similar appearance, taste, and consistency, but without the active components	After a month, the test gel showed improved antibacterial and Peri-implant mucositis effects than the control group
Son et al[28]; in vitro	Propolis-embedded zeolite nanocomposites, PLA/PCL polymer pellets, and dental implants fabricated from these materials	This study explored the potential of propolis-embedded zeolite nanocomposites for use in dental implants	- Sustained release - Antibacterial activity - Cytotoxicity - Overall efficacy	Propolis-embedded zeolite nanocomposites powder	Chlorhexidine (CHX) powder and empty zeolite nanocomposites	Dental implants with propolis-embedded zeolite nanocomposites have antibacterial qualities and low toxicity, making them ideal for dental and orthopedic applications due to their biocompatibility
SanaUllah et al[29]; in vitro	NR	To synthesize honey-mediated zirconia using a microwave-assisted sol–gel method and evaluate its suitability for bone implant applications	Mechanical properties, biocompatibility, biodegradation behavior, antibacterial activity, and antioxidant potential, ultimately assessing its suitability for use as a bone implant substitute	Honey-mediated zirconia nano-powders	Zirconia nanofibers powder	Honey-mediated zirconia exhibits strong antioxidant activity. Thus, honey-mediated zirconia can be successfully used for bone implants
Krasnikov et al[9]; in vivo and in vitro	In vivo 8 rabbit In vitro 10 samples Fibroblast	The study's goal is to examine the osseointegration capabilities of a polymer composite thermooxidized coating modified with flavonoid nanoaggregates, which are biocompatible and capable of rapidly bioresorbing in vivo without producing toxic compounds or causing unfavorable body reactions	1) Biointegration properties of the experimental implants, such as body temperature, animal behavior, limb support ability, compression response, and the presence of swelling/exudate 2) Hematological markers such as leukocyte numbers and C-reactive protein serve as indicators of the inflammatory response to implants	Rabbits were implanted with multilayer films of titanium dioxide, polyaziridine-ammonium, and flavonoid nanoaggregates combined with propolis	Rabbits were implanted with titanium dioxide-coated implants	In vitro cell culture and in vivo animal tests show that a biodegradable implant covering comprising 1.25 mg/mL propolis and no more than 0.0001% polymer, modified with flavonoid nanoaggregates and halogen hydrate ions, is non-toxic and biocompatible. The coating did not hinder cell adhesion or proliferation, nor did it have any deleterious impact on the animals' blood or metabolic markers
Udduttula et al[30]; in vitro	NR	The goal of this study was to create multilayered coatings of jellyfish-derived collagen and hyaluronic acid (HA) on titanium alloy (Ti64) substrates, and to incorporate the antibacterial agent methylglyoxal (MGO) from Manuka honey into the coatings to improve their anti-infection efficacy	- Antibacterial activity against E. coli and S. epidermidis bacteria was assessed by planktonic and biofilm quantification, live/dead staining, and SEM analysis. - The cytocompatibility of MGO-loaded HA/J-COLL coatings was assessed using metabolic activity, live/dead staining, cytoskeleton staining, and SEM analysis on L929 fibroblast cells. - The osteogenic differentiation of Y201 immortalized human mesenchymal stem cells (hMSCs) on the MGO-loaded HA/J-COLL coatings	Antibacterial agent-methylglyoxal from Manuka honey was incorporated into layer-by-layer collagen and hyaluronic acid (HA) coatings on Ti64 alloy substrates.	- Titanium alloy (Ti64) samples were coated with comparable layer-by-layer assemblies of jellyfish-derived collagen and HA, but did not contain methylglyoxal - Uncoated 3-aminopropyl triethoxysilane-Ti64 substrates were also used for comparison to determine baseline parameters	The methylglyoxal-loaded hyaluronic acid/jellyfish-derived collagen coatings on Ti64 alloy substrates created in this study can perform as an effective antibacterial coating while simultaneously promoting bone formation, making them a suitable choice for orthopedic implants and bone tissue engineering applications
Abdulla et al[2]; in vivo	72 implants placed in 24 dogs	The study aimed to determine the effect of several surface treatments (sandblasting, sandblasting plus acid etching, Er, Cr:YSGG laser, and propolis coating) on the osseointegration of titanium dental implants in dogs, both with and without occlusal loading. 180 d	1) Radiographic evaluation of osseointegration. 2) Histological evaluation of osseointegration and bone remodeling 3) Bone cell count (osteoblasts, osteocytes, and osteoclasts) The implants were examined at three periods following installation: • Group I: 14 days (unloaded implants) • Group II: 90 days (unloaded implants) • Group III requires 180 days (loaded implants)	Propolis coating	- Sandblasting and acid etching (SLActive) group - Sandblasting using aluminum oxide (Al2O3) group - Er and Cr: YSGG laser therapy group	The various surface treatments for dental implants, including sandblasting, sandblasting plus acid etching, Er, Cr:YSGG laser, and propolis coating, had a substantial impact on osseointegration and bone remodeling. The sandblasting and propolis coating groups had the best bone response and maturation, particularly under delayed loading conditions
Abdulla et al[31]; in vivo	16 dogs, 48 titanium implants	Evaluated implant stability (ISQ) and serum cortisol levels during stress and surface treatments	- Implant stability quotient (ISQ): Measured at baseline (time of implant installation), 14 days, and 90 days using the Easy Check device. - Serum cortisol levels: Used as a biomarker for stress, measured at baseline and periodically up to 90 days, using an ELISA kit. Secondary outcomes - Body weight changes: Recorded every 15 days - Bone remodeling and healing: Indirectly evaluated through changes in ISQ and observations of bone integration	Propolis coating. The test and control groups were further divided into two subgroups: Group I: Non-stressed group (n = 8 dogs). Group II: Stressed group (n = 8 dogs)	- Sandblasting and acid etching (SLActive) group - Sandblasting using aluminum oxide (Al2O3) group - Er and Cr:YSGG laser therapy group	Surface treatment determines the ISQ and stress effects. Sandblasting provided the greatest results
Zahid et al[10]; in vitro	- Freshly prepared AgNO3 (1 mM) was added to a 15-mL honey solution in a different volumetric ratio	The research effort intended to improve the surface properties of metallic materials, specifically titanium implants, in order to increase mechanical stability and clinical osseointegration	Bacterial biofilm suppression and bone tissue integration	Honey-based silver nanoparticles (HNY-AgNPs)	- Mesoporous silica nanoparticles - HNY-Ag Mesoporous silica nanoparticles hybrid	The findings suggest that HNY-AgNPs-MSN hybrid implants could serve as an effective design for advanced dental implants, enhancing antibacterial properties and potentially improving clinical outcomes
Al-Molla et al[32]; in vivo	Pure titanium implants were implanted in the tibias of 40 rabbits	Examined the expression of osteocalcin (OC) and type I collagen as markers of bone formation in propolis-coated and uncoated implants over 1, 2, 4, and 6-wk intervals	Histological and immunohistochemical examinations for OC and type I collagen expression	Rabbits implanted with pure titanium implants coated with propolis protein	Rabbits implanted with pure titanium implants uncoated with propolis protein	Implants coated with propolis greatly enhanced osseointegration

Abbreviations: API, approximal plaque index; EHS, early wound healing index; HNY-AgNPs, honey-based silver nanoparticles; ISQ, implant stability quotient; OC, osteocalcin; OHI, oral hygiene index; NR, not reported; BOP, bleeding on probing; PI, plaque index; PD, probing depth; PLA/PCL, poly(L-lactide)/poly(ε-caprolactone); PL-TNT-Ti, propolis-loaded TNT Ti implants; SEM, scanning electron microscope; TNT, TiO₂ nanotubes.

Main Findings and Descriptive Analysis of Studies

Antibacterial and Antifungal Efficacy

Multiple studies demonstrated the potent antimicrobial properties of propolis and honey-based interventions.[8] [10] [25] [27] [28] [29] [30] Brazilian red propolis effectively inhibited Candida biofilms on titanium surfaces, while honey-based silver nanoparticles exhibited strong antibacterial activity against Staphylococcus aureus and Streptococcus mutans.[10] [25]

Osseointegration, Bone Healing, and Biocompatibility

Studies evaluating propolis-modified titanium implants reported enhanced bone remodeling and mineral density. Propolis-loaded TiO₂ nanotubes significantly improved new bone growth and reduced inflammation, while honey-mediated zirconia demonstrated unique mechanical properties suitable for osseointegration.[11] [23]

Advanced coatings incorporating propolis or honey derivatives enhanced implant stability and resisted bacterial colonization.[9] [30] Layer-by-layer coatings with Manuka honey's antibacterial agent methylglyoxal (MGO) supported both antibacterial activity and osteogenic differentiation.[30] Coated titanium implants with propolis showed earlier bone formation, mineralization, and maturation compared with controls. Osteoblast cells on these implants exhibited positive reactions for osteocalcin (OC) and type I collagen, indicating that the addition of biological materials enhanced bone formation and maturation.[32]

Propolis solutions reduced oxidative stress and promoted antioxidant activity in both local and systemic applications. Biocompatibility assessments revealed minimal cytotoxicity and effective osteoblast proliferation, making these interventions promising for clinical use.[23]

Survival and Success Rates and Other Clinical Outcomes

In clinical trials, propolis-containing gels and toothpastes have shown improvements in parameters such as plaque indices, gingival bleeding, and the resolution of peri-implant mucositis.[26] [27] Chlorhexidine gel has remained the gold standard for soft tissue healing, but oxygen-enriched alternatives have shown potential.[26]

Propolis-based implant modifications improved bone density, new bone formation, and reduced inflammation, indicating stronger early integration.[11] [32] Animal studies also showed superior osseointegration, enhanced bone maturation, and higher ISQ values, particularly under delayed loading.[2] [31] These outcomes collectively suggest a positive influence on long-term implant success.

More detailed findings are summarized in [Table 4].

Table 4 Main findings of included studies

Study	Main findings
Morawiec et al[8]	• OHID index medians: Propolis toothpaste (3%)—0.2, control—0.08 (no significant differences) • Approximal Plaque Index: Greater reduction in propolis group, achieving “optimal hygiene” (87.5%) • Bleeding index: No significant differences • Taste and smell: Control preferred • Propolis toothpaste: Improved oral health, reduced gingivitis, potential adjunct for periodontal risk
Aydin et al[23]	• Superoxide dismutase activity: Higher in propolis groups (0.4196 U/g local, 0.4205 U/g systemic) vs. control (0.4034 U/g), no significant difference • Catalase level: Significantly higher in systemic group (1.8633 k/g) vs. control (0.4390 k/g) • Malondialdehyde levels: Significantly lower in propolis groups (16.2883 nmol/mg local, 15.9766 nmol/mg systemic) vs. control (26.0676 nmol/mg) (p < 0.05) • Reduced glutathione levels: Higher in propolis groups (181.0928 U/g local, 383.6860 U/g systemic) vs. control (151.6390 U/g) (p < 0.05) • Vitamin D levels: Significantly increased in both propolis groups (p < 0.05)
Somsanith et al[11]	• Bone mineral density: Higher in PL-TNT-Ti (11.2 g/cm2) vs. TNT (9.7 g/cm2) at 4-wk follow-up • New bone volume: Increased in PL-TNT-Ti (12.26 mm3) vs. TNT (9.67 mm3) • Inflammatory cytokines: IL-1β and TNF-α decreased around PL-TNT-Ti, indicating reduced inflammation • Bone morphogenetic proteins: Higher BMP-2 and BMP-7 expression around PL-TNT-Ti, suggesting enhanced osteogenic differentiation • Propolis-loaded TiO2 nanotubes: Promoted osseointegration, reduced inflammation in dental implants
Kakaa et al[24]	• Corrosion behavior of commercially pure titanium (cp-Ti) grade 2 evaluated in artificial saliva with fluoride ions and propolis extract as inhibitors • Fluoride increased corrosion current density (Icorr) from 0.33 to 7.69 µA/cm2 • Propolis extract (1 mg/mL) reduced Icorr to 0.48 µA/cm2, achieving 93.75% inhibition efficiency • SEM analysis: Effective coverage and adhesion of propolis on titanium surfaces • Propolis adsorption followed the Langmuir isotherm, confirming enhanced corrosion resistance in fluoride environments
Martorano-Fernandes et al[25]; in vitro	• Brazilian red propolis inhibited mono-species and co-culture biofilms of Candida albicans and Candida glabrata on titanium surfaces • Chlorhexidine (0.12%) and red propolis (3%) reduced cell viability and metabolic activity of mono-species biofilms (p < 0.05) • In co-culture biofilms, chlorhexidine showed the highest inhibition, while red propolis reduced metabolic activity less effectively • Surface roughness measurements: Both treatments significantly reduced biofilm presence vs. control • Brazilian red propolis: Promising alternative for peri-implantitis treatment due to antifungal properties
Priyadarshini et al[26]	• Mean EHS scores on day 1: Blue M gel (4.30 ± 2.3), Chlorhexidine (6.0 ± 1.9) • Mean EHS scores on day 7: Blue M gel (7.0 ± 2.3), chlorhexidine (8.1 ± 2.1) • No statistically significant differences between groups on either day (p = 0.272, p = 0.245) • Chlorhexidine gel showed higher mean EHS scores, confirming its role as the gold standard for soft tissue healing after dental implant surgery
González-Serrano et al[27]	• Complete resolution of peri-implant mucositis: 26.1% of patients, 25% of implants in test group vs. 0% in control (p = 0.02) • Clinical parameter reductions in the test group: • PI: ↓ 27.85% (p = 0.03) • BOP: ↓ 27.78% (p = 0.04) • Modified bleeding index: 0.56 → 0.13 (p = .002) • PD: ↓ 0.85 mm (p = 0.027) • Width of keratinized tissue: ↑ 0.51 mm (p = 0.05) • Tannerella forsythia significantly reduced (p = 0.02), Porphyromonas gingivalis decreased (p = 0.05) • No adverse effects reported, confirming the test gel's efficacy and safety
Son et al[28]	• Propolis-embedded zeolite nanocomposites released propolis continuously for 1 mo • PLA/PCL pellets showed longer sustained release • Nanocomposite powder exhibited significant antibacterial activity against Candida albicans, similar to chlorhexidine • Eluted propolis solution from PLA/PCL pellets remained effective against Streptococcus mutans and Streptococcus sobrinus • PLA/PCL-based dental implants with nanocomposites showed negligible cytotoxicity, confirming biocompatibility • Nanocomposites identified as promising candidates for infection prevention in dental implants
SanaUllah et al[29]	• Pure tetragonal zirconia formed at 100 and 200 W, stabilized by honey • Zirconia nanofibers: High hardness (∼1,510 HV), fracture toughness (∼28.80 MPa·m1/2) • Dielectric constant: ∼73, increasing to 82.5 at higher temperatures • Biodegradation: Minimal weight loss after 26 wk, indicating strong bone-bonding bioactivity • Antibacterial activity: Highest inhibition zone against E. coli ∼33 mm • Honey-mediated zirconia: Promising for bone implants due to enhanced mechanical and antioxidant properties
Krasnikov et al[9]	• Implants with 1.25 mg/mL propolis and low polymer concentration exhibited good biointegration without toxicity • High fibroblast adhesion and proliferation at effective concentrations; higher concentrations inhibited cell growth • In vivo results: Significant cellular adhesion and bone tissue integration after 30 d • Hematological analysis: No acute inflammatory responses, biochemical stability maintained • Normal levels of calcium, phosphorus, and liver enzymes • No significant health differences in rabbits post-implantation • Favorable properties for dental implants
Udduttula et al[30]	• Layer-by-layer coatings of collagen-hyaluronic acid with methylglyoxal from Manuka honey showed effective antibacterial properties and cytocompatibility • Methylglyoxal incorporated into multilayer coatings on Ti64 substrates, with controlled release over 21 d • Significant inhibition of E. coli and S. epidermidis • In vitro: No adverse effects on L929 fibroblast metabolic activity, increased cell proliferation • Promoted differentiation of Y201 mesenchymal stem cells, reduced biofilm formation • Methylglyoxal-loaded hyaluronic acid/collagen coatings enhance antibacterial performance and support bone regeneration in implants
Abdulla et al[2]	• Significant new bone formation along implant surfaces, with smooth osseointegration in 68 implants (radiographic analysis) • Histological findings: Uniform bone growth with many osteoblasts after 14 d • At 90 d: increased bone ingrowth, new bone maturation, particularly in sandblasting and propolis groups • At 180 d: notable differences in remodeling among treatment groups, with remarkable changes in the propolis coating group • Surface modifications, especially propolis coating, significantly impacted osseointegration
Abdulla et al[31]	• Non-stressed group: Sandblasting yielded the highest ISQ (88) at 90 d, while sandblasting with acid etching had the lowest (82.6) at 14 d • Stressed group: Sandblasting had the highest ISQ (88.3), laser treatment had the lowest (72) • Stressed group: Significantly higher serum cortisol levels (195.33 ng/mL) compared to the non-stressed group (143.10 ng/mL) at 90 d • Non-stressed group gained weight, stressed group showed significant weight loss, indicating stress effects on implant stability • Findings highlight the importance of surface modifications and stress management in optimizing osseointegration
Zahid et al[10]	• Honey-based silver nanoparticles (HNY-AgNPs) synthesized with a surface plasmon resonance peak at 413 nm • HNY-AgNPs: Average size 144 nm, polydispersity index (PDI) 0.319, indicating good colloidal stability • FTIR analysis confirmed silver nanoparticle stabilization by honey • Antibacterial tests: HNY-AgNPs are effective against Staphylococcus aureus and Streptococcus mutans • HNY-AgNPs-MSN hybrid implants: Potential for advanced dental implants, enhancing antibacterial properties and improving clinical outcomes
Al-Molla et al[32]	• Propolis-coated implants exhibited significant bone formation with thick trabeculae, indicating enhanced osseointegration • Weak positive OC expression was observed in both propolis-coated and uncoated implants, suggesting stabilization in bone formation • Negative type I collagen expression was noted in propolis-coated implants, while uncoated implants showed weak positive expression in osteoblasts • Propolis coating facilitated earlier bone mineralization and maturation compared to uncoated implants

Abbreviations: API, approximal plaque index; EHS, early wound healing index; HNY-AgNPs, honey-based silver nanoparticles; ISQ, implant stability quotient; OC, osteocalcin; OHI, oral hygiene index; NR, not reported; BOP, bleeding on probing; PI, plaque index; PD, probing depth; PLA/PCL, poly(L-lactide)/poly(ε-caprolactone); PL-TNT-Ti, propolis-loaded TNT Ti implants; SEM, scanning electron microscope; TNT, TiO₂ nanotubes.

Discussion

Multiple surface-modification strategies and biological additives show promise for improving dental implant performance. This review assessed innovative approaches using honey- and propolis-derived components, which demonstrate strong potential for enhancing osseointegration and implant management. Propolis consistently reduces inflammation, improves osseointegration, and provides antibacterial and antioxidant effects essential for healing and infection control. Honey-based formulations—especially Manuka honey and nanoparticle systems—also enhance antibacterial activity and support osseointegration. Additional materials, such as flavonoid nanoaggregates, further enhance biocompatibility without compromising toxicity, thereby contributing to long-term implant stability. Comparative treatments, such as sandblasting, offer strong osseointegration outcomes, while silver nanoparticles provide superior antibacterial performance.

Propolis has proven to be an effective biomaterial with versatile applications, serving as an anti-inflammatory agent that significantly reduces inflammation, as demonstrated in implant coating studies.[2] [11] Propolis-containing toothpaste improves oral health and reduces gingivitis,[8] while its combination with calcium hydroxide shows anti-inflammatory and regenerative effects.[36] Yellow propolis–modified cements also support favorable healing responses,[37] and propolis with bovine bone graft enhances socket healing after tooth extraction by modulating osteogenic markers,[38] supporting its value as a bioactive adjunct in restorative and implant-related procedures. It presents a natural alternative for managing periodontal problems in implant-supported prosthodontics. Systemic administration showed superior results, and local applications of propolis significantly reduced oxidative stress and enhanced bone repair in implant surgeries.[23] Propolis with nano vitamin C and E gels significantly improved peri-implant mucositis management and reduced pathogenic bacterial levels.[27]

Titanium implants modified with propolis-loaded nanotubes promoted better osseointegration and reduced inflammation than plain titanium implants by promoting bone growth and minimizing inflammation. These findings were consistent across in vitro and in vivo assessments.[11] Furthermore, propolis improved the corrosion resistance and enhanced the durability of titanium implants in artificial fluoride-rich saliva, enhancing their longevity in oral environments.[24] In addition, Brazilian red propolis has antibacterial and antifungal effectiveness and effectively inhibits Candida biofilms and oral pathogens, offering a potentially suitable alternative for treating peri-implantitis.[25]

Propolis-embedded zeolite nanocomposite materials demonstrated vigorous antibacterial activity and low toxicity, making them ideal for implant production.[28] Recently, Abdulla et al highlighted the efficacy of propolis-coated implants in enhancing osseointegration and bone remodeling, particularly under delayed loading conditions.[2] In contrast to some studies, such as those on propolis-containing gels, which noted that clinical results for peri-implant mucositis depend heavily on concentrations and adjunctive therapies.[27]

Honey, particularly Manuka honey, offers unique advantages as antibacterial efficacy, especially Manuka honey's methylglyoxal (MGO) content incorporated into layer-by-layer coatings of biomolecules (e.g., hyaluronic acid and collagen) loaded with Manuka honey for titanium alloys, which have antibacterial properties and proven effective against Escherichia coli, S. mutans, and other pathogens while supporting tissue regeneration. These coatings demonstrated superior osteogenic potential compared to basic polymer-based materials.[10] Honey-mediated zirconia nanofibers showed potential for bone implant applications due to antioxidant activity and mechanical properties, which improve osseointegration.[29] Additionally, honey-based coatings have high cytocompatibility and promote cell proliferation and osteogenic differentiation, making them ideal for both soft tissue healing and bone integration.[30] However, honey formulations may require precise optimization of concentrations to avoid cytotoxicity or biofilm resistance, and the potential for improving the surface properties of titanium implants and honey-based silver nanoparticles (AgNPs) hybrid implants showed excellent antibacterial activity; while effective, they can be limited by cytotoxicity at higher concentrations compared with natural alternatives.[10]

Other innovative biomaterials provide distinct benefits and complement honey and propolis applications as coatings containing flavonoid nano-aggregates combined with titanium implants, enhancing biointegration without adverse biological reactions.[9] They share similarities with propolis in reducing inflammatory cytokines and promoting cell adhesion.

Chlorhexidine (CHX) gel outperformed oxygen-enriched blue-M gel and is considered a gold standard for soft tissue healing and biofilm management after implant placement. However, the differences were not statistically significant.[26] However, long-term use raises concerns about resistance and cytotoxicity compared with natural alternatives like propolis and honey.

The 15 studies included in this evaluation revealed that many investigations were conducted, particularly on animal and in vitro experiments,[8] [11] [23] and they had small sample sizes, which limited the statistical power of their results, reducing confidence in the generalizability of their findings. Although several other clinical studies[26] [27] showed better bias control than laboratory and animal studies, they had short follow-up periods. This limits the ability to assess long-term outcomes, particularly for osseointegration and implant stability. While animal studies were informative for preliminary testing,[31] it often lacked details about randomization, blinding, and allocation concealment. Studies should provide detailed methodologies to improve reproducibility and credibility, including randomization techniques, allocation concealment, and statistical analyses.

Laboratory and in vitro studies demonstrated promising results but lacked clinical validation, raising questions about their applicability in real-world settings.[25] [28] The present study revealed that both clinical and animal studies need larger sample sizes to enhance the reliability of their conclusions and reduce variability. Animal and laboratory studies should consistently use randomization and blinding to minimize detection and performance biases. Studies should extend follow-up periods to assess the durability of interventions, particularly for osseointegration and soft tissue healing, and in vitro studies demonstrating efficacy should progress to clinical settings to evaluate real-world outcomes.

Strengths of Evidence, Limitations, and Recommendations

The overall strength of the evidence is assessed as moderate, reflecting variability in study design, methodological rigor, and sample size. Among the three randomized clinical trials, two exhibited a low risk of bias, while one displayed a moderate risk. All in vivo and in vitro studies indicated a moderate risk of bias, primarily attributable to limitations in blinding, allocation procedures, and reporting transparency. The small sample sizes across nearly all studies further diminish statistical power and constrain generalizability. Additionally, short follow-up periods, the absence of sample size calculations and blinding in all in vivo and in vitro studies, and the lack of randomization in the in vitro experiments contribute to these limitations. Furthermore, the generalizability of the findings is restricted. Consequently, future investigations should prioritize the inclusion of a greater number of clinical trials and real-world clinical studies. Additional research with larger sample sizes is essential to ascertain long-term effects and address organoleptic concerns. By addressing these limitations, future research can provide more robust evidence to inform clinical decision-making in implantology.

Conclusion

This systematic review found that honey- and propolis-based agents demonstrate antibacterial, healing, and osseointegration-enhancing effects across in vitro and animal studies. Propolis generally showed stronger anti-inflammatory and osseointegration-related outcomes, while honey exhibited notable antibacterial activity. However, the current evidence is predominantly preclinical, and limited clinical data prevent drawing firm conclusions about their effectiveness in improving dental implant success or survival. Well-designed comparative clinical studies are needed to clarify their therapeutic potential and to determine their appropriate applications in dental implant therapy.

Conflict of Interest

None declared.

Acknowledgments

We would like to express our gratitude to the Department of Clinical Science, College of Dentistry, Ajman University, Ajman, UAE, for their support in covering the publication fee for this manuscript.

Authors' Contributions

A.Y.A., G.A.A., R.S.A.: Data curation, methodology, visualization, writing and reviewing the original draft, writing and reviewing, formal analysis, and supervision.

G.A.A., Y.S.R.: Conceptualization, data curation, methodology, project administration, formal analysis, writing and reviewing, and supervision.

Y.S.R., H.O.A, S.A.W., S.A.E., M.H.S.: Data resources, methodology, visualization, writing, and reviewing primary draft.

Data Availability Statement

The data will be available upon request from the authors.

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Publication History

Article published online:
23 January 2026