BACKGROUND: Loss of the dental and paradental tissues resulting from trauma, caries or from systemic diseasesconsidered as one of the most significant and frequent clinical problem to the healthcare professionals. Great attempts havebeen implemented to recreate functionally, healthy dental and paradental tissues in order to substitute dead and diseasedtissues resulting from secondary trauma of car accidents, congenital malformations of cleft lip and palate or due to acquireddiseases such as cancer and periodontal involvements.METHOD: An extensive literature search has been done on PubMed database from 2010 to 2019 about the challenges ofengineering a biomimetic tooth (BioTooth) regarding basic biology of the tooth and its supporting structures, strategies,and different techniques of obtaining biological substitutes for dental tissue engineering. RESULTS: It has been found that great challenges need to be considered before engineering biomimetic individual parts of thetooth such as enamel, dentin-pulp complex and periodontium. In addition, two approaches have been adopted to engineer aBioTooth.The first one was to engineer a BioTooth as an individual unit and the other was to engineer a BioToothwith its supporting structures. CONCLUSION Engineering of BioTooth with its supporting structures thought to be in the future will replace the traditionaland conventional treatment modalities in the field of dentistry. To accomplish this goal, different cell lines and growthfactors with a variety of scaffolds at the nano-scale level are now in use. Recent researches in this area of interest arededicated for this objective, both in vivo and in vitro. Despite progress in this field, there are still many challenges ahead andneed to be overcome, many of which related to the basic tooth biology and its supporting structures and some others related tothe sophisticated techniques isolating cells, fabricating the needed scaffolds and obtaining the signaling molecules.

BACKGROUND: Loss of the dental and paradental tissues resulting from trauma, caries or from systemic diseasesconsidered as one of the most significant and frequent clinical problem to the healthcare professionals. Great attempts havebeen implemented to recreate functionally, healthy dental and paradental tissues in order to substitute dead and diseasedtissues resulting from secondary trauma of car accidents, congenital malformations of cleft lip and palate or due to acquireddiseases such as cancer and periodontal involvements.METHOD: An extensive literature search has been done on PubMed database from 2010 to 2019 about the challenges ofengineering a biomimetic tooth (BioTooth) regarding basic biology of the tooth and its supporting structures, strategies,and different techniques of obtaining biological substitutes for dental tissue engineering. RESULTS: It has been found that great challenges need to be considered before engineering biomimetic individual parts of thetooth such as enamel, dentin-pulp complex and periodontium. In addition, two approaches have been adopted to engineer aBioTooth.The first one was to engineer a BioTooth as an individual unit and the other was to engineer a BioToothwith its supporting structures. CONCLUSION Engineering of BioTooth with its supporting structures thought to be in the future will replace the traditionaland conventional treatment modalities in the field of dentistry. To accomplish this goal, different cell lines and growthfactors with a variety of scaffolds at the nano-scale level are now in use. Recent researches in this area of interest arededicated for this objective, both in vivo and in vitro. Despite progress in this field, there are still many challenges ahead andneed to be overcome, many of which related to the basic tooth biology and its supporting structures and some others related tothe sophisticated techniques isolating cells, fabricating the needed scaffolds and obtaining the signaling molecules.

BACKGROUND: Dentin is a permeable tubular composite and complex structure, and in weight, it is composed of 20% organic matrix, 10% water, and 70% hydroxyapatite crystalline matrix. Demineralization of dentin with gradient concentrations of ethylene diamine tetraacetic acid, 0.6 N hydrochloric acid, or 2% nitric acid removes a major part of the crystalline apatite and maintains a majority of collagen type I and non-collagenous proteins, which creates an osteoinductive scaffold containing numerous matrix elements and growth factors. Therefore, demineralized dentin should be considered as an excellent naturally-derived bioactive material to enhance dental and alveolar bone tissues regeneration.METHOD: The PubMed and Midline databases were searched in October 2021 for the relevant articles on treated dentin matrix (TDM)/demineralized dentin matrix (DDM) and their potential roles in tissue regeneration. RESULTS: Several studies with different study designs evaluating the effect of TDM/DDM on dental and bone tissues regeneration were found. TDM/DDM was obtained from human or animal sources and processed in different forms (particles, liquid extract, hydrogel, and paste) and different shapes (sheets, slices, disc-shaped, root-shaped, and barrier membranes), with variable sizes measured in micrometers or millimeters, demineralized with different protocols regarding the concentration of demineralizing agents and exposure time, and then sterilized and preserved with different techniques.In the act of biomimetic acellular material, TDM/DDM was used for the regeneration of the dentin-pulp complex through direct pulp capping technique, and it was found to possess the ability to activate the odontogenic differentiation of stem cells resident in the pulp tissues and induce reparative dentin formation. TDM/DDM was also considered for alveolar ridge and maxillary sinus floor augmentations, socket preservation, furcation perforation repair, guided bone, and bioroot regenerations as well as bone and cartilage healing. CONCLUSION To our knowledge, there are no standard procedures to adopt a specific form for a specific purpose; therefore, future studies are required to come up with a well-characterized TDM/DDM for each specific application. Likely as decellularized dermal matrix and prospectively, if the TDM/DDM is supplied in proper consistency, forms, and in different sizes with good biological properties, it can be used efficiently instead of some widely-used regenerative biomaterials.

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023.The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogenactivated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp–like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.