There has been an increase in research interest and application of treated dentin matrix (TDM) in vital pulp therapy (VPT) in recent years. TDM has excellent biocompatibility and contains transforming growth factor-β, bone morphogenetic protein 2, and other odontogenesis/osteogenesis-related proteins and factors that promote odontogenic differentiation of dental stem cells. TDM-based products, ranging from powders and pastes to injectable composite gels and gel scaffolds, have gained increasing consensus for their ability to induce dentin-like tissue regeneration. Animal and clinical studies found that TDM has significant advantages over traditional pulp capping materials, as it can form well-organized layers of odontoblast-like cells and uniform dentinal tubule structures. Future challenges of TDM in VPT application are primarily focused on improving mechanical properties and addressing potential immune rejection issues with heterologous material use. Additionally, further studies should be conducted on the odontogenetic pathway mechanism of TDM and the immune regulatory capabilities of xenogeneic dentin matrix materials. Utilizing TDM to construct tissue engineering scaffolds for VPT presents a promising strategy. This article reviews the structure and biological properties of TDM and related materials, thoroughly examines their progresses in the field of VPT, and discusses their current challenges as well as future research directions.

Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive reactive oxygen species (ROS) expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS. In this study, xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H₂O₂)-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and superoxide dismutase 1 (SOD1) knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft. It showed that RSG pretreatment significantly reduced the adverse effects of H₂O₂ on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency, maximumly maintaining the xenograft function. We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress (OS) microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.