The Role of Growth Factor Delivery Systems on Cellular Activities of Dental Stem Cells: A Systematic Review (Part II)

Objective: The current systematic review aims to provide the available ex vivo evidence evaluating the biological interactions of dental stem cells (DSCs) and growth factor delivery systems. Methods: Following the Preferred Reporting Items for a Systematic Reviews and Meta-Analyses (PRISMA) guidelines, systematic search was conducted in the electronic databases (PubMed/Medline, Scopus, Web of Science, and Google Scholar) up to January 2022. Studies evaluating the biological interactions of DSCs and growth factor delivery systems were included. The outcome measures were cell cytocompatibility, mineralization, and differentiation. Results: Sixteen studies were selected for the qualitative synthesis. The following growth factor delivery systems exhibit adequate cytocompatibility, enhanced mineralization, and osteo/odontoblast differentiation potential of DSCs: 1) Fibroblast growth factor (FGF-2)-loaded-microsphere and silk fibroin, 2) Bone morphogenic protein-2 (BMP-2)-loaded-microsphere and mesoporous calcium silicate scaffold, 3) Transforming growth factor Beta 1 (TGF-ß1)-loaded-microsphere, glass ionomer cement (GIC), Bio-GIC and liposome, 4) TGF-ß1-loaded-nanoparticles/scaffold, 5) Vascular endothelial growth factor (VEGF)-loaded-fiber and hydrogel, 6) TGF-ß1/VEGF-loaded-nanocrystalline calcium sulfate/hydroxyapatite/calcium sulfate, 7) Epidermal growth factor-loaded- nanosphere, 8) Stem cell factor/DSCs-loaded-hydrogel and Silk fibroin, 9) VEGF/BMP-2/DSCs-loaded-Three-dimensional matrix, 10) VEGF/DSCs-loaded-microsphere/hydrogel, and 11) BMP-2/DSCs and VEGF/DSCs-loaded-Collagen matrices. The included delivery systems showed viability, except for Bio-GIC on day 3. The choice of specific growth factors and delivery systems (i.e., BMP-2-loaded-microsphere and VEGF-loaded-hydrogel) resulted in a greater gene expression. Conclusions: This study, with low-level evidence obtained from ex vivo studies, suggests that growth factor delivery systems induce cell proliferation, mineralization, and differentiation toward a therapeutic potential in regenerative endodontics.