Decellularized bone extracellular matrix and human dental pulp stem cells as a construct for bone regeneration

Abstract

Dental pulp tissue represents a source of mesenchymal stem cells that have a strong differentiation potential towards the osteogenic lineage. The objective of the current study was to examine in vitro osteogenic induction of dental pulp stem cells (DPSCs) cultured on hydrogel scaffolds derived from decellularized bone extracellular matrix (bECM) compared to collagen type I (Col-I), the major component of bone matrix. DPSCs in combination with bECM hydrogels were cultured under three different conditions: basal medium, osteogenic medium and medium supplemented with growth factors (GFs) and cell growth, mineral deposition, gene and protein expression were investigated. The DPSCs/bECM hydrogel constructs cultured in basal medium showed that cells were viable after three weeks and that the expression of runt-related transcription factor 2 (RUNX-2) and bone sialoprotein (BSP) were significantly upregulated in the absence of extra osteogenic inducers compared to Col-I hydrogel scaffolds. In addition, the protein expression levels of BSP and osteocalcin were higher on bECM with respect to Col-I hydrogel scaffolds. Furthermore, DPSCs/bECM hydrogels cultured with osteogenic or GFs supplemented medium displayed a higher upregulation of the osteo-specific markers compared to Col-I hydrogels in identical media. Collectively, our results demonstrate that bECM hydrogels might be considered as suitable scaffolds to support osteogenic differentiation of DPSCs.

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

“…Dental MSC-CM could further provide a valuable tool for liver regeneration. The presence of hepatic lineage proteins 19 Stem Cells International GAS6 in the secretome of dental pulp MSCs, MSCs from the apical papilla, and dental follicle MSCs and different LDL receptor (LRP) proteins in the secretome of dental pulp MSCs and MSCs from the apical papilla reflected their role in controlling lipid metabolism and transport as well as hepatic differentiation. Interestingly, oncostatin M and hepatocyte growth factor receptor, which are important inducers for hepatic lineage differentiation were detected solely in dental follicle MSC secretome [64].…”

“…In the same context, decellularization was introduced as a novel scaffold fabrication technique that depends on maintaining the extracellular matrix with its organization, architecture, and vascular network, thus obtaining a cell-free 3D structure harboring biological signals, affecting the cell behavior and differentiation [17]. Different methods were proposed for such decellularization process, including the employment of detergents, enzymes, and salts combined with some physical means [18], producing a biological scaffold, ready to be seeded by the desired cell type for different tissue engineering purposes [19,20].…”

Oral Mesenchymal Stem/Progenitor Cells: The Immunomodulatory Masters

“…Extracellular matrix (ECM) is also considered a crucial factor to influences oral MSCs by changing its biochemical or physical properties. Compared to collagen type I which is the most commonly purified ECM, decellularized bone extracellular matrix (bECM) hydrogels facilitated a significant upregulation of RUNX-2 and bone sialoprotein (BSP) of DPSCs, indicating their osteogenic differentiation [61]. Physical factors of ECM, such as stiffness, could influence the distribution and morphology of DPSCs and promote their odontogenic and osteogenic differentiation [62].…”

Management of Endodontic and Periodontal Lesions: the Role of Regenerative Dentistry and Biomaterials

“…Recently, the scaffolds' vascularization has been investigated by using a novel approach, called engineered cells without scaffolds (CSE): this technique works to create and provide an adequate environment for graft vascularization. In the CSE technique, the cells are organized in sheets and overlapped to improve the cell density; this is allowed by a better vascularization of the graft, able to ensure greater efficiency of the scaffold during its role to regenerate bone tissue [16].…”