Currently, there is much discussion regarding the biomineralization/mineralization/remineralization process in dental tissues, as there has been an increase in the development of novel bioinspired materials aimed at restoring the mineral loss of damaged dental structures. These materials are capable of partially reproducing mineral formation by mimicking biomolecular functionality or stabilizing mineral phases involved in the mineralization process [1].

Certain peptides have been designed to self-assemble into hierarchical structures and possess high affinity for inorganic molecules, allowing them to directly control the morphology, size, and composition of mineralized materials [2]. Since their discovery in 1989 [3], self-assembling peptides have been used in various applications, ranging from surfactant materials to wound healing in regenerative medicine [3,4].

The self-assembling P11–4 peptide (Ace-QQRFEWEFEQQ-NH2), is bioinspired in the amelogenin telopeptide at the C-terminal, and involves 11 amino acids capable of forming antiparallel β-sheet structures under specific triggers [5]. In dentistry, this peptide has been investigated for its application in enamel remineralization, in a non-classical way, also known as biomimetic remineralization [6]. Its use has been studied in the treatment of initial caries on enamel [7] and in promoting remineralization of dentin when its use has promoted the remineralization of the dentin-like caries affected on dentin/resin interface [8]. Previous research has also shown that dentin conditioned with P11–4 is a potent inhibitor of the proteolytic activity of collagen fibrils and is able to enhance the collagen thickness of dentin [9]. With regard to the association of this peptide with cells, recent evidence has shown its success in periodontal regeneration [10], its ability to induce cell migration and mineral deposition of odontoblast-like cells (MDPC-23) similarly to DMP1 [11], and its ability to increase the in vivo osteo-regeneration after 8 weeks [12].

The use of mesenchymal stem cells (MSCs) for regenerative purposes are extensively explored, often in combination with cell-responsive materials. That way, stem cells from the apical papilla (SCAPs) have been a promising source for tissue engineering since their discovery by Sonoyama et al. in 2006 [13]. These cells, also known as “pad-like tissue”, can be easily extracted from the immature root of third molars (Fig. 1A-B). In addition, recent findings suggest superior plasticity and potency compared to those of Dental Pulp Stem Cells (DPSCs)[14]. Moreover, they demonstrate higher mineralization capacity [15] and can be differentiated into an odontoblastic lineage [16].

In order to induce mineral deposition by cells, the peptide must be able to induce cell migration and differentiation, as well. During this process, mesenchymal stem cells undergo a transformation from a non-specific state, to a morphologically and functionally specific state, ultimately resulting in the production of extracellular matrix and formation of mineral nodules. In the field of dentistry, the mineralization process induced by the peptide may have potential therapeutic applications as a replacement for calcium hydroxide in tooth repair, such as in pulp capping, with the long-term goal of promoting tooth regeneration [11].

This is a well-designed study that aims to fill an important gap in the literature regarding the use of P11–4 as a mineralization inducer of SCAPs. The hypothesis of the study is that P11–4 at low concentrations (less than 100 µg/ml) will induce osteogenic differentiation of SCAPs and mineral deposition without causing a cytotoxic effect. The study uses quantitative real-time polymerase chain reaction (qPCR) to analyze the expression of three osteogenic genes (RUNX2, ALP, and OCN) and alizarin red staining to assess mineral deposition over a period of 30 days. Overall, the study has the potential to contribute to the development of new strategies for tooth repair and regeneration.