3.1.2. Dentin Formation

Dentin regeneration is most often related to a treatment of the dentin-pulp complex. Since pulp vitality is essential for tooth homeostasis and stability, strategies to maintain this vitality are highly desirable. Presently, pulp capping is the main therapy maintaining the pulp vitality but is frequently accompanied by irreversible pulp inflammation and reinfections [16]. Thus, innovative approaches and biomaterials for the regeneration of the pulp–dentin complex are highly desirable.

In classical endodontic therapy via apexification, the pulp space is initially cleared and sealed with calcium hydroxide or MTA to induce a hard-tissue formation at the apical area that is used as a barrier for a permanent root filling material. Since this procedure does not promote further root development, root canal walls remain thin and fragile, leading to teeth that are prone to further issues [135]. To overcome these limitations, regenerative endodontic therapies including revascularization are being developed. Here, bleeding is induced to fill the endodontic canal and form an autologous blood clot that serves as a sca ffold homing matrix proteins, (stem) cells, and growth factors, which consequently leads to the regeneration of the pulp–dentin complex due to root development, apical closure, and maintenance of the tooth vitality [17,136]. However, due to the presence of mesenchymal stem cells in the infiltrating blood, the generated tissue is more bone-like mixed with connective tissue instead of the desired pulp–dentin complex [137].

Recently, Mandakhbayar and colleagues used strontium-free and strontium-containing nanobioactive glass cement in a pulp capping approach to evaluate their potential to regenerate the pulp–dentin complex in vitro and in vivo [138]. The nanobiocement based on mesoporous calcium silicate nanobioactive glasses showed a fast release of Ca-, Sr-, and Si-ions, which are known for their bioactive properties in hard-tissue regeneration; promoted the odontogenesis of DPSCs in vitro; and showed promising results in vivo, especially for Sr-containing biomaterials [138]. Boron-modified bioactive glass nanoparticles were embedded in an organic matrix of cellulose acetate, oxidized pullulan, and gelatin by Moonesi-Rad and associates to build a dentin-like construct by freeze-drying and subsequent mold pressing [139]. The composite material induced the enhanced deposition of a calcium phosphate layer after immersion in simulated body fluid. Moreover, cell culture studies using DPSCs indicated the promotive e ffects of boron-modified bioactive glasses on attachment, migration, and odontogenic di fferentiation [139]. In a classical ternary system comprising an injectable collagen sca ffold, DPSCs, and growth factors, Pankajakshan and coworkers evaluated the e ffect of mechanical properties of the collagen matrix [140]. Via concentric injection, the authors created a sca ffold with an inner section of lower sti ffness, which is covered with an outer section of higher sti ffness to mimic

the mechanical properties of the natural pulp–dentin complex. Additionally, they loaded the softer sca ffold material with proangiogenetic vascular endothelial growth factor (VEGF) and the sti ffer sca ffold material with BMP2 to enhance the site-specific endothelial or odontogenetic di fferentiation of DPSCs, respectively. The results show that the sti ffness of the materials regulates the direction of DPSCs di fferentiation. This e ffect is further enhanced by the loading of the collagen matrices with VEGF or BMP2, respectively [140].
