Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis:therapeutic potential for endogenous pulp regeneration

Pulp loss is accompanied by the functional impairment of defense,sensory,and nutrition supply.The approach based on endogenous stem cells is a potential strategy for pulp regeneration.However,endogenous stem cell sources,exogenous regenerative signals,and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells.Therefore,the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration.In in vitro study,we investigated the effects of Wnt3a,transforming growth factor-beta 1,and bone morphogenetic protein 7(BMP7)on human dental pulp stem cells(h-DPSCs)and human umbilical vein endothelial cells.2D and 3D culture systems based on collagen gel,matrigel,and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs.In in vivo study,an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7.We concluded that BMP7promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation.Collagen gel maintained the cell adhesion,cell spreading,and cell viability of h-DPSCs in 2D or 3D culture.The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo.The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.

Tooth regeneration: a revolution in stomatology and evolution in regenerative medicine

A tooth is a complex biological organ and consists of multiple tissues including the enamel, dentin, cementum and pulp. Tooth loss is the most common organ failure. Can a tooth be regenerated？ Can adult stem cells be orchestrated to regenerate tooth structures such as the enamel, dentin, cementum and dental pulp, or even an entire tooth？ If not, what are the therapeutically viable sources of stem cells for tooth regeneration？ Do stem cells necessarily need to be taken out of the body, and manipulated ex vivo before they are transplanted for tooth regeneration？ How can regenerated teeth be economically competitive with dental implants？ Would it be possible to make regenerated teeth affordable by a large segment of the population worldwide？ This review article explores existing and visionary approaches that address some of the above-mentioned questions. Tooth regeneration represents a revolution in stomatology as a shift in the paradigm from repair to regeneration： repair is by metal or artificial materials whereas regeneration is by biological restoration. Tooth regeneration is an extension of the concepts in the broad field of regenerative medicine to restore a tissue defect to its original form and function by biological substitutes.

Dental pulp stem cells and BonelikeVR for bone regeneration in ovine model

Development of synthetic bone substitutes has arisen as a major research interest in the need to find an alternative to autologous bone grafts.Using an ovine model,the present pre-clinical study presents a synthetic bone graft(BonelikeVR)in combination with a cellular system as an alternative for the regeneration of non-critical defects.The association of biomaterials and cell-based therapies is a promising strategy for bone tissue engineering.Mesenchymal stem cells(MSCs)from human dental pulp have demonstrated both in vitro and in vivo to interact with diverse biomaterial systems and promote mineral deposition,aiming at the reconstruction of osseous defects.Moreover,these cells can be found and isolated from many species.Non-critical bone defects were treated with BonelikeVR with or without MSCs obtained from the human dental pulp.Results showed that BonelikeVR and MSCs treated defects showed improved bone regeneration compared with the defects treated with BonelikeVR alone.Also,it was observed that the biomaterial matrix was reabsorbed and gradually replaced by new bone during the healing process.We therefore propose this combination as an efficient binomial strategy that promotes bone growth and vascularization in non-critical bone defects.

Cells and material-based strategies for regenerative endodontics

The carious process leads to inflammation of pulp tissue.Current care options include root canal treatment or apexification.These procedures,however,result in the loss of tooth vitality,sensitivity,and healing.Pulp capping and dental pulp regeneration are continually evolving techniques to regenerate pulp tissue,avoiding necrosis and loss of vitality.Many studies have successfully employed stem/progenitor cell populations,revascularization approaches,scaffolds or material-based strategies for pulp regeneration.Here we outline advantages and disadvantages of different methods and techniques which are currently being used in the field of regenerative endodontics.We also summarize recent findings on efficacious peptide-based materials which target the dental niche..