Mineral trioxide aggregate (MTA) is a highly biocompatible calcium silicate-based cement (CSC) that demonstrates positive clinical outcomes in endodontic procedures [1], [2]. MTA was the first CSC used in endodontics, and since then, various types of MTA have been developed [3]. MTA is used as pulp capping as an alternative to Ca(OH)2, as it induces dentin development and reduces pulp inflammation [4], [5]. Moreover, MTA possesses several advantageous physical properties compared to Ca(OH)2, such as improved sealing, reduced solubility, and greater structural stability [2]. Therefore, MTA has recently been defined as the new gold standard in several endodontic procedures [6]. However, MTA still presents several drawbacks, including challenging handling, extended setting time, poor adhesion to hard dental tissues, and potential for discoloration of the crown [7], [8], [9]. Improving these CSCs’ physiochemical properties and enhancing apatite precipitation bioactivity have driven new-generation CSCs [10], [11].

Indeed, a modern CSC known as Biodentine™️ (BD: Septodont, Saint-Maur des Fosses, France) was introduced in 2009 to improve some of the disadvantages aforementioned [12]. BD exhibited a shorter setting time and significantly reduced discoloration compared to conventional MTA, due to the absence of bismuth oxide and the additive of CaCl2 acting as an accelerator and regulated the setting reaction [13], [14]. However, BD still presents challenges in handling, does not adhere well to hard dental tissues, and its long-term in vivo effectiveness as a pulp-capping treatment remains uncertain [9].

In a recent study, it has been proposed that MTA containing phosphorylated pullulan (PPL) does not present some of the typical issues of CSCs, particularly the lack of adhesion to hard dental tissues, along with the difficult handling properties [15]. Pullulan (PL) is a polymer derived from the fermentation of black yeast [16]. As a potential biomaterial, pullulan offers several advantages due to its non-toxic nature and the availability of hydroxyl groups within the pyranose rings for substitution with phosphate groups [17], [18]. Therefore, phosphorylated pullulan (PPL) has been expected as a carrier for growth factors for bone tissue engineering, where its strong chemical bond that forms between the phosphate groups and hydroxyl group contributes to adhesion with hard tissue [19]. Some studies have already demonstrated that MTA containing PPL (MTA-PPL) exhibits favorable bioactivities, including an excellent healing response in pulp tissue and the ability to induce complete mineral tissue formation when used as a direct pulp capping material [9], [20], [21].

On the other hand, inorganic polyphosphate (polyP) is composed solely of a chain of phosphate groups connected by high-energy bonds. Perhaps interestingly, this compound is present in every organism and plays roles in a multitude of cellular processes, including phosphate storage, blood coagulation, and pathogenicity [22]. PolyP has been identified in human osteoblasts and is known to have several beneficial effects on bone tissue [23]. It also positively influences apoptosis and the mineralization process [24]. Furthermore, PolyP promotes intracellular calcification, the maturation of bone-related immature cells, and contributes to bone tissue deposition by osteoblasts; it induces alkaline phosphatase (ALP) activity, as well as upregulates the gene expression of osteocalcin and osteopontin [25]. PolyP present enhanced antibacterial properties and dentin-inductive properties, depending on its molecular size (chain length). PolyP is classified into long-chain (polyPL), medium-chain (polyPM), and short-chain (polyPS). It has been advocated that polyPM enhances fibroblast growth factor (FGF) function, accelerates tissue regeneration and bone regeneration, and inhibits bone resorption by osteoclasts, whereas polyPL showed similar activity as polyPM but act as a more efficient inhibitor of bone resorption and inducible nitric oxide, NO, synthase (iNOS) expression [26]. Moreover, polyPS has been demonstrated to be highly effective in preventing staining of the tooth surface and suppressing its demineralization by binding to the tooth surface [27]. Therefore, polyPS has most potential to strongly adhere to hydroxyapatite (HAp) compared with the other polyP with different chain lengths [28].

This laboratory study aimed to evaluate the solubility, pH, calcium ion release, initial and final setting times, and HAp deposition bioactivity of various MTA cements doped with poly-PS or PPL compared to two commercial cements (MTA and BD). The hypothesis being tested in this study was that the incorporation of polyPS or PPL in an MTA cement would enhance its physicochemical and apatite precipitation behavior.