Non-Cochrane · intervention · PM41494731
Bioactive molecule delivery platforms in regenerative endodontic therapy: A systematic review and meta-analysis.
Kaur Kanwalpreet, Binduhayyim Rayan Ibrahim H, Saini Ravinder S, et al. · Cell transplantation · 2026 · PubMed · doi:10.1177/09636897251407385
Findings
19 findings
| Population | ||||
|---|---|---|---|---|
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Cell viability (24-72 h) Laboratory and animal experiments · Model stratum IV/EV; I2 58% | SMD 0.48 [0.32, 0.63] Low Downgraded: risk of bias, imprecision, inconsistency, indirectness 22 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Mineralization (alizarin/calcein) Laboratory and animal experiments · Sensitivity analysis excluding non-endodontic or off-target tissue models; Model stratum IV/EV; I2 58% | SMD 0.33 [0.15, 0.5] GRADE not reported 12 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Vascularization/angiogenesis markers Laboratory and animal experiments · Model stratum IV/Animal; I2 49% | SMD 0.31 [0.08, 0.53] Very low Downgraded: risk of bias, imprecision, inconsistency, indirectness 7 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Adverse events/toxicology Laboratory and animal experiments · Model stratum Animal; I2 21% | RR 0.92 [0.68, 1.25] GRADE not reported 6 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Overall pooled (primary regenerative composite) Laboratory and animal experiments · Model stratum All applicable; I2 59% | SMD 0.41 [0.29, 0.53] GRADE not reported 47 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Alkaline phosphatase (ALP) activity Laboratory and animal experiments · Sensitivity analysis excluding non-endodontic or off-target tissue models; Model stratum IV/EV; I2 55% | SMD 0.4 [0.24, 0.56] GRADE not reported 16 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Cell viability (24-72 h) Laboratory and animal experiments · Sensitivity analysis excluding non-endodontic or off-target tissue models; Model stratum IV/EV; I2 52% | SMD 0.45 [0.3, 0.6] GRADE not reported 20 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Antimicrobial outcomes (log10 CFU reduction) Laboratory and animal experiments · Sensitivity analysis excluding non-endodontic or off-target tissue models; Model stratum IV/EV; I2 53% | MD -0.75 [-1.02, -0.48] GRADE not reported 17 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Histologic regeneration Laboratory and animal experiments · Sensitivity analysis excluding non-endodontic or off-target tissue models; Model stratum Animal; I2 38% | RR 1.58 [1.16, 2.16] GRADE not reported 8 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Vascularization/angiogenesis markers Laboratory and animal experiments · Sensitivity analysis excluding non-endodontic or off-target tissue models; Model stratum IV/Animal; I2 45% | SMD 0.29 [0.07, 0.51] GRADE not reported 6 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Adverse events/toxicology Laboratory and animal experiments · Sensitivity analysis excluding non-endodontic or off-target tissue models; Model stratum Animal; I2 18% | RR 0.89 [0.66, 1.22] GRADE not reported 5 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Overall pooled (primary regenerative composite) Laboratory and animal experiments · Sensitivity analysis excluding non-endodontic or off-target tissue models; Model stratum All applicable; I2 54% | SMD 0.39 [0.28, 0.51] GRADE not reported 41 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Alkaline phosphatase (ALP) activity Laboratory and animal experiments · Model stratum IV/EV; I2 61% | SMD 0.42 [0.25, 0.58] Low Downgraded: risk of bias, imprecision, inconsistency, indirectness 18 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Antimicrobial outcomes (log10 CFU reduction) Laboratory and animal experiments · Model stratum IV/EV; I2 57% | MD -0.78 [-1.05, -0.51] GRADE not reported 20 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Mineralization (alizarin/calcein) Laboratory and animal experiments · Model stratum IV/EV; I2 64% | SMD 0.36 [0.18, 0.54] Very low Downgraded: risk of bias, imprecision, inconsistency, indirectness 14 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Intracanal delivery platform (hydrogel, nanogel, polymeric nanoparticle, liposome, mesoporous silica) loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Histologic regeneration Laboratory and animal experiments · Model stratum Animal; I2 42% | RR 1.62 [1.18, 2.23] Low Downgraded: risk of bias, imprecision, inconsistency 9 studies |
| Dental pulp stem cells (in vitro) | Growth factor loaded scaffold (sustained delivery) | Growth factor in solution | Alkaline phosphatase (ALP) activity 7 days · Laboratory and animal experiments | Pooled standardized mean difference indicated significantly higher ALP induction with sustained delivery (P < 0.01); numeric estimate not reported GRADE not reported 3 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Aquasome delivery platform loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Regenerative endpoints (viability, ALP, mineralization, histology, vascularization) Laboratory and animal experiments | No experimental study using aquasomes in a dental model was found No studies found 0 studies |
| Tooth or pulp models (dental pulp stem cells, SCAP, tooth slices, animal teeth) in vitro, ex vivo or in animals | Vesosome delivery platform loaded with a bioactive payload | Blank scaffold, scaffold-free procedure (blood clot) or solution delivery | Regenerative endpoints (viability, ALP, mineralization, histology, vascularization) Laboratory and animal experiments | No experimental study using vesosomes in a dental model was found No studies found 0 studies |
Included primary studies 28
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Ahmadi 2021 G-CSF augments the neuroprotective effect of conditioned medium of dental pulp stem cells against hypoxic neural injury in SH-SY5Y cells. PMID:35432810 | 2021 | this review only | not stated | not extracted yet |
| Asheghi 2025 Chitosan nanogels enriched with granulocyte-macrophage colony-stimulating growth factor promote odontoblastic differentiation in human… PMID:40597938 | 2025 | this review only | not stated | not extracted yet |
| Bottino 2013 Bioactive Nanofibrous Scaffolds for Regenerative Endodontics DOI:10.1177/0022034513505770 | 2013 | this review only | not stated | not extracted yet |
| Bottino 2013 Bioactive nanofibrous scaffolds for regenerative endodontics. PMID:24056225 | 2013 | this review only | not stated | not extracted yet |
| Caballero-Flores 2021 Development and characterization of a new chitosan-based scaffold associated with gelatin, microparticulate dentin and genipin for… DOI:10.1016/j.dental.2021.03.016 | 2021 | this review only | not stated | not extracted yet |
| Caballero-Flores 2021 Development and characterization of a new chitosan-based scaffold associated with gelatin, microparticulate dentin and genipin for… PMID:33867170 | 2021 | this review only | not stated | not extracted yet |
| Elnawam 2024 Preparation and characterization of bovine dental pulp-derived extracellular matrix hydrogel for regenerative endodontic applications: an… PMID:39448989 | 2024 | this review only | not stated | not extracted yet |
| Galler 2012 A Customized Self-Assembling Peptide Hydrogel for Dental Pulp Tissue Engineering DOI:10.1089/ten.tea.2011.0222 | 2012 | this review only | not stated | not extracted yet |
| Galler 2012 A customized self-assembling peptide hydrogel for dental pulp tissue engineering. PMID:21827280 | 2012 | this review only | not stated | not extracted yet |
| Gonciarz 2025 Chitosan-based formulations for therapeutic applications. A recent overview. PMID:40629425 | 2025 | this review only | not stated | not extracted yet |
| Ji 2021 Preparation of bioactive glass nanoparticles with highly and evenly doped calcium ions by reactive flash nanoprecipitation. PMID:33891166 | 2021 | this review only | not stated | not extracted yet |
| Kamocki 2015 Dental pulp stem cell responses to novel antibiotic‐containing scaffolds for regenerative endodontics DOI:10.1111/iej.12414 | 2014 | this review only | not stated | not extracted yet |
| Kamocki 2015 Dental pulp stem cell responses to novel antibiotic-containing scaffolds for regenerative endodontics. PMID:25425048 | 2015 | this review only | not stated | not extracted yet |
| Kashi 2012 Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method. PMID:22275837 | 2012 | this review only | not stated | not extracted yet |
| Momose 2016 Collagen Hydrogel Scaffold and Fibroblast Growth Factor-2 Accelerate Periodontal Healing of Class II Furcation Defects in Dog. PMID:27583044 | 2016 | this review only | not stated | not extracted yet |
| Murray 2018 Platelet-Rich Plasma and Platelet-Rich Fibrin Can Induce Apical Closure More Frequently Than Blood-Clot Revascularization for the… PMID:30364277 | 2018 | this review only | not stated | not extracted yet |
| Ruparel 2012 Direct Effect of Intracanal Medicaments on Survival of Stem Cells of the Apical Papilla DOI:10.1016/j.joen.2012.06.018 | 2012 | this review only | not stated | not extracted yet |
| Ruparel 2012 Direct effect of intracanal medicaments on survival of stem cells of the apical papilla. PMID:22980180 | 2012 | this review only | not stated | not extracted yet |
| Shrestha 2015 Temporal-controlled Dexamethasone Releasing Chitosan Nanoparticle System Enhances Odontogenic Differentiation of Stem Cells from Apical… DOI:10.1016/j.joen.2015.03.024 | 2015 | this review only | not stated | not extracted yet |
| Shrestha 2015 Temporal-controlled Dexamethasone Releasing Chitosan Nanoparticle System Enhances Odontogenic Differentiation of Stem Cells from Apical… PMID:25956605 | 2015 | this review only | not stated | not extracted yet |
| Sinjari 2019 Curcumin/Liposome Nanotechnology as Delivery Platform for Anti-inflammatory Activities via NFkB/ERK/pERK Pathway in Human Dental Pulp… DOI:10.3389/fphys.2019.00633 | 2019 | this review only | not stated | not extracted yet |
| Talaat 2024 Regenerative potential of mesoporous silica nanoparticles scaffold on dental pulp and root maturation in immature dog's teeth: a… PMID:39026199 | 2024 | this review only | not stated | not extracted yet |
| Watcharadulyarat 2023 PEG-PLGA nanoparticles for encapsulating ciprofloxacin. PMID:36609594 | 2023 | this review only | not stated | not extracted yet |
| Wu 2019 Evaluation of Chitosan Hydrogel for Sustained Delivery of VEGF for Odontogenic Differentiation of Dental Pulp Stem Cells. PMID:31949434 | 2019 | this review only | not stated | not extracted yet |
| Yan 2021 Potential apply of hydrogel-carried chlorhexidine and metronidazole in root canal disinfection DOI:10.4012/dmj.2020-299 | 2021 | this review only | not stated | not extracted yet |
| Yan 2021 Potential apply of hydrogel-carried chlorhexidine and metronidazole in root canal disinfection. PMID:33883328 | 2021 | this review only | not stated | not extracted yet |
| Zhang 2020 Alginate/laponite hydrogel microspheres co-encapsulating dental pulp stem cells and VEGF for endodontic regeneration DOI:10.1016/j.actbio.2020.07.012 | 2020 | this review only | not stated | not extracted yet |
| Zhang 2020 Alginate/laponite hydrogel microspheres co-encapsulating dental pulp stem cells and VEGF for endodontic regeneration. PMID:32663663 | 2020 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Tooth or pulp models in vitro, ex vivo or animal; RET or dental pulp regeneration | 47 studies (32 in vitro/ex vivo, 10 animal, 5 clinical/clinical ex vivo) (n=47) |
| Intervention | Defined intracanal delivery platform with a bioactive payload (hydrogel, nanogel, nanoparticle, liposome, mesoporous silica) | Hydrogels, nanogels, polymeric nanoparticles, liposomes, aquasomes, vesosomes, mesoporous silica nanoparticles |
| Comparison | Blank scaffold, scaffold-free procedure (blood clot), or solution delivery | Blank scaffold, blood clot, solution delivery or free drug |
| Outcomes | Regenerative endpoints: viability, ALP activity, mineralization, histology, vascularization, functional readouts; antimicrobial endpoints; adverse events | Cell viability, ALP activity, mineralization, histologic regeneration, vascularization, antimicrobial effect, adverse events |
| Study designs | In vitro, ex vivo, animal and clinical studies | In vitro, ex vivo, animal and clinical studies (n=47) |
| Timing | Not specified | Not specified |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: N/A · NRSI: Partial Yes | NRSI: Partial Yes · RCT: N/A | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: N/A · NRSI: No | NRSI: No · RCT: N/A | no |
| 12Impact of risk of bias on the pooled results | No | No | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | No | Yes | no |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |