Understanding dentinogenesis and pulp regeneration during physiological and pathological conditions represents a real challenge in the provision of a suitable treatment that ideally leads to the induction of the pulp regenerative potential. This paper focusses on the early steps of dentin–pulp regeneration that appear to be critical after pulp capping procedures. Different models are described in this paper where the interactions between different cell types in vitro illustrate their role in maintaining pulpal homeostasis. After traumatic injuries, the cells modify the local pulpal microenvironment by secreting growth factors that orchestrate and induce the processes required for dentin–pulp regeneration. Applying dental materials onto the injured pulp modifies this local microenvironment and affects the potential for pulpal regeneration. The paper also describes the added value of developing an entire human tooth culture model for understanding these early steps and discusses the interest of its use in evaluating newly developed pulp capping materials through the example of BiodentineTM, developed as a dentin substitute. The growth factors sustained release simulating the local microenvironment is also discussed. Simulating the pulp local environment with a continuous growth factors release is also a basic requirement for establishing future pulp tissue engineering.