Bioprinting Hydrogels for Dentin Pulp Regeneration and Disinfection

Oral and maxillofacial complications pose challenges due to issues like lack of material biocompatibility and invasive treatments. One common example is the endodontic treatment, where the infected pulp is removed. Bacteria and their byproducts that interact with host tissues in the dental pulpal and periradicular regions are the primary cause of endodontic pathosis. The elimination of microorganisms from the root canal system (RCS) is essential for effective endodontic therapy. This process can leave the tooth brittle in the long-term. Because they can promote, in a biologically based framework, the continuation of root development and apical closure, regenerative endodontic therapies (RETs) in necrotic immature teeth have drawn a lot of interest recently. Getting a sufficient disinfection of the root canal system is a must for success in RETs since bacterial persistence in root canals in such instances considerably impede healing and root maturation. Moreover, additive manufacturing can facilitate the development of hydrogels that can regenerate lost dentin pulp, restoring tooth strength and longevity and achieve sustainable drug release. This research aimed to identify a scaffold, which possesses optimal degradability, chemical, mechanical, cytocompatible features, that can deliver antibiotics or induce stem cell differentiation for regenerative endodontic treatment while maintaining durability. For this purpose, methacrylated Pluronic polymers were chosen due to their well researched drug releasing capabilities, as well as their potential injectability, stemming from their reverse thermo-responsive nature.<br/>Initially, the studies focused on F127-DMA and F88-DMA hydrogels and their crosslinking efficiency with two photoinitiators (Irgacure- 651 and 2959). Different assays, such as mechanical properties characterization by rheology, swelling ratio, crosslinking efficiency and drug release analysis, were conducted. Crosslinking was mediated by UV lamp and by 3D printer (BioX 3D Bioprinter) where the durability of the constructs was researched. Irgacure 2959 showed superiority both in terms of crosslinking efficiency (~16% difference) and mechanical stiffness. Comparing both Pluronics, the data collected showed that F88 had a higher swelling ratio than F127. Elastic modulus measurements confirmed that F127 was inherently stronger, and its cross-linking efficiency was superior due to its lower swelling ratio. Aiming at imparting degradability, the Pluronic were end capped with L-Lactide prior to methacrylation and similar studies were conducted throughout prolonged time incubated in aqueous medium at 37 degrees. The lactide-containing matrixed exhibited elevated swelling until full degradation after several weeks, demonstrating the rapid degradability. Furthermore, aiming at exploring drug release capabilities, release profiles of Clindamycin, Metronidazole and Ciprofloxacine (Triple paste antibiotic) were researched.<br/>In conclusion, while F127's stiffness and effective crosslinking make it a promising candidate in terms of mechanical features and F88’s hydrophilic properties and favorable degradation profile also make it a favorable option in regards to hydrophilic affinity and mass loss, further research is required to assess the biocompatibility of photoinitiators and their concentrations in terms of cell viability. Thus, further studies will be conducted on the hydrogels’ bio-printability, cell viability, cytotoxicity, antibacterial efficiency of drugs added and osteogenic differentiation or the ability of stem cells to differentiate into bone cells. The gels developed will present multiple potential endodontic applications: it could be placed on the top of the pulp cavity to induce dentin regeneration or disinfect the canal area. Thus, these hydrogels will ultimately pave the way for more potent dental treatment approaches.