A Customized Self-Assembling Peptide Hydrogel-Wrapped Stem Cell Factor Targeting Pulp Regeneration Rich in Vascular-Like Structures

Abstract

Pulp regeneration is to replace the inflamed/necrotic pulp tissue with regenerated pulp-like tissue to rejuvenate the teeth. Self-assembling peptide hydrogels RADA16-I (Ac-(RADA16-I) 4 -CONH 2 ) can provide a three-dimensional environment for cells. The stem cell factor (SCF) plays a crucial role in homing stem cells. Combining these advantages, our study investigated the effects of SCF-RADA16-I on adhesion, proliferation, and migration of human dental pulp stem cells (DPSCs) and the angiogenesis of human umbilical vein endothelial cells (HUVECs). The β-sheet and grid structure were observed by circular dichroism (CD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Cytoskeleton staining, living cell staining, cell viability, cell migration, angiogenesis, and western blot assays were performed, and the results indicated that all the SCF groups were superior to the corresponding non-SCF groups in cell adhesion, proliferation, migration, and angiogenesis. RADA16-I provided a three-dimensional environment for DPSCs. Besides, the SCF promoted HUVECs to form more vascular-like structures and release more vascular endothelial growth factor A. In summary, the SCF-loaded RADA16-I scaffold improved adhesion, proliferation, and migration of DPSCs and the formation of more vascular-like structures of HUVECs. SCF-RADA16-I holds promise for guided pulp regeneration, and it can potentially be applied widely in tissue engineering and translational medicine in the future.

Angiogenesis in Regenerative Dentistry: Are We Far Enough for Therapy?

“…The most known multipotent cell is the mesenchymal stem cells (MSCs). MSCs are described as promoters, enhancers, and playmakers in dental regenerative medicine [ 10 ]. The MSCs are able to differentiate into various tissues: adipose tissue, bone, cartilage, or muscles [ 19 , 20 , 21 , 22 ].…”

“…Endodontic angiogenesis is crucial to the long-term survival of regenerated pulp. The regeneration of pulp tissue rich in vascular-like structures is essential for restoring tooth vitality, process sustained by different injectable peptide scaffold wrapping the stem cell factor, that permit pulp regeneration rich in vascular-like structures [ 10 ].…”

Hydrogels and Dentin–Pulp Complex Regeneration: From the Benchtop to Clinical Translation

“…For dentin–pulp complex regeneration, hydrogels act as carriers of stem/progenitor cells with odontogenic potential, such as DPSCs [ 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ], odontoblasts-like cells [ 68 , 69 , 70 ], HUVECs [ 64 , 71 ], SCAP [ 72 , 73 ], SHED [ 66 , 74 , 75 , 76 ], BMMSCs [ 66 , 77 , 78 , 79 , 80 ], PDLSCs [ 66 ], endothelial cells [ 78 ] and primary dental pulp cells [ 81 ]. They can also act as carriers for the local delivery of antibiotics, such as clindamycin [ 82 ] and bioactive molecules, aiming to promote tissue regeneration, such as VEGF [ 20 , 61 , 83 ], FGF [ 20 , 83 , 84 , 85 ], BMP [ 65 ], TGF-β1 [ 20 , 86 ], stem cell factor [ 87 ], dentonin sequence [ 88 ] and RGD cell-binding motifs [ 56 , 89 ]. Once implanted in site, being biodegradable, hydrogels allow the release of bioactive molecules that influence the surrounding environment [ 90 , 91 ] ( Figure 3 ).…”

“…Self-assembling RADA16-I peptide hydrogels can be modified by the addition of bioactive molecules to enhance dentin–pulp complex regeneration [ 87 , 88 ]. Self-assembling peptide hydrogel RADA16-I, incorporated with stem cell factor and loaded with DPSCs and HUVECs, was effective in promoting cell adhesion, proliferation, migration and angiogenesis in vitro [ 87 ].…”

“…Self-assembling RADA16-I peptide hydrogels can be modified by the addition of bioactive molecules to enhance dentin–pulp complex regeneration [ 87 , 88 ]. Self-assembling peptide hydrogel RADA16-I, incorporated with stem cell factor and loaded with DPSCs and HUVECs, was effective in promoting cell adhesion, proliferation, migration and angiogenesis in vitro [ 87 ]. Injectable self-assembled peptide hydrogel modified through the incorporation of dentonin sequence, a bioactive component of ECM phospho-glycoprotein, was biocompatible and supported DPSCs proliferation and mineralization in vitro [ 88 ].…”