Objectives: Vital pulp therapy (VPT) is shifting from traditional materials toward regenerative strategies that modulate inflammation and stimulate angiogenesis. This review evaluates scaffold-based, scaffold-free, and cell-laden approaches targeting immunomodulatory and angiogenic responses in dental pulp regeneration.
Materials and methods: systematic search up to April 2025 in PubMed, Embase, and Scopus identified in vivo studies assessing VPT outcomes. Included interventions were direct pulp capping or pulpotomy using bioactive scaffolds, biomolecules, or stem cell-laden matrices. Outcomes included histologic or molecular markers of immunomodulation and angiogenesis. Risk of bias was assessed using the SYRCLE tool.
Results: Twenty-six studies met the inclusion criteria. Scaffold-based delivery of Resolvin E1/lipoxin A4, Nell-1, and Nell-1/BMP-2 suppressed key inflammatory mediators and promoted M2 macrophage polarization. Angiogenesis was enhanced by cell-laden scaffolds containing dental pulp stem cells, bone marrow mesenchymal stem cells, or endothelial cells, leading to consistent pulp-like tissue regeneration. However, most studies had short follow-ups, high or unclear bias risk, and methodological heterogeneity, precluding meta-analysis. Interpretation of these findings should be undertaken with caution due to substantial heterogeneity in study design, outcome assessment methods, and evaluation time points.
Conclusions: Biomolecule-loaded and stem cell-laden scaffolds show preliminary promise in modulating inflammation and promoting vascularization in animal models of VPT. However, evidence remains limited by short-term outcomes and inconsistent methods.
Clinical relevance: Scaffold-based delivery of Resolvin E1, Lipoxin A4, or Nell-1/BMP-2, and stem cell-laden matrices (e.g., DPSCs, BMSCs) may enhance immunomodulation and angiogenesis in preclinical VPT. These strategies could support pulp-like tissue regeneration, but standardized outcome measures and validation in large-animal models are needed before clinical application.
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