Regenerative medicine is an innovative field of medicine that is also developing in dental and maxillofacial sciences. Dental-derived mesenchymal stem cells (D-dMSC) are an intriguing milestone of the regenerative medicine, with regard to their potential of differentiating into osteogenic, adipogenic, and chondrogenic lineages. Healing occurs when the regenerated tissue has been integrated into the neighboring host tissue and the differentiation process has been thoroughly performed. Complete healing might be achieved by establishing novel strategies of using scaffolds in combination with pretreated and/or untreated mesenchymal stem cells in the presence of selective differentiation factors.

In regenerative medicine, the stem cells secretome, in particular for mesenchymal stem/stromal cells, is increasingly considered as a main promoter of the beneficial effects of stem cell transplantation. Bioengineered/biomimetic scaffolds, engineered peptide, and protein materials provide the advantages of a biological matrix with the control of a synthetic polymer. They could be considered a merger of the two, retaining the bioactivity of harvested protein materials, like collagen and fibrin, with the control and tunability of synthetic, chemically defined materials, such as poly(ethylene glycol) (PEG) and poly(lactic-co-glycolic acid) (PLGA).

Following this approach, peptide-loaded tHA (tHA/pep) particles blended with scaffolds provide a temporary mechanical and vascular support for tissue regeneration while tissue in-growth is being formed. However, much still needs to be elucidated, in order to be able to create efficient and safe bioartificial substitutes for clinical use.

In this special issue, we invite worldwide researchers as well as the clinicians confident in the translational regenerative medicine to submit their most interesting overviews, reviews, and original papers describing the good, the bad, and the ugly of D-dMSC interactions with scaffolds and biomaterials, including investigation on the potential of mesenchymal stem cell secretome and its manipulation, for the development of regenerative medicine approaches.

Potential topics include but are not limited to the following:

• Mesenchymal stem cells in translational research and therapeutic strategies towards tissue regeneration and wound healing
• Growth factors effects on mesenchymal stem cells
• Mesenchymal stem cells delivery/routes
• The importance of three-dimensional cell culture models (e.g., hydrogels) for understanding cell-ECM interactions in most tissue types
• Use of stem cells secretome or its components in immunomodulatory strategies, to promote tissue repair/regeneration
• Extracellular matrix and bioactive molecules
• Stem cells based on bioscaffold tissue models
• Impact of biomaterials structure and composition on stem cell behavior and differentiation
• Computational models investigating the mechanobiology of D-dMSC and their interactions with scaffolds for tissue engineering

Clinical research on application of D-dMSC and their cross talk with engineered peptide and protein materials, including bioengineered/biomimetic scaffolds, secretome, feasibility, and “proof-of-concept” studies, new methodological paradigms that challenge current thinking in clinical research, and development of clinical-grade D-dMSC in matrix remodeling under good manufacturing practice protocols/conditions as an essential step towards clinical application and other similar studies are warmly welcome topics.