Dental pulp is a highly specialized mesenchymal tissue that has a limited regeneration capacity due to anatomical arrangement and postmitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that has demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article reviews the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and provides insightful information to readers about the different aspects involved in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The findings collected in this literature review show that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable goal and the next decade will certainly be an exciting time for dental and craniofacial research.

Tissue engineering is an interdisciplinary field that combines the principles of engineering, material and biological sciences toward the development of therapeutic strategies and biological substitutes that restore, maintain, replace or improve biological functions. The association of biomaterials, stem cells, growth and differentiation factors have yielded the development of new treatment opportunities in most of the biomedical areas, including Dentistry. The objective of this paper is to present the principles underlying tissue engineering and the current scenario, the challenges and the perspectives of this area in Dentistry. Significance The growth of tissue engineering as a research field have provided a novel set of therapeutic strategies for biomedical applications. The emerging knowledge arisen from studies in the dental area may translate into new methods for caring or improving the alternatives used to treat patients in the daily clinic.

Objectives The clinical translation of stem cell-based Regenerative Endodontics demands further development of suitable injectable scaffolds. Puramatrix™ is a defined, self-assembling peptide hydrogel which instantaneously polymerizes under normal physiological conditions. Here, we assessed the compatibility of Puramatrix™ with dental pulp stem cell (DPSC) growth and differentiation. Methods DPSC cells were grown in 0.05 to 0.25% Puramatrix™. Cell viability was measured colorimetrically using the WST-1 assay. Cell morphology was observed in 3-D modeling using confocal microscopy. In addition, we used the human tooth slice model with Puramatrix™ to verify DPSC differentiation into odontoblast-like cells, as measured by expression of DSPP and DMP-1. Results DPSC survived and proliferated in Puramatrix™ for at least three weeks in culture. Confocal microscopy revealed that cells seeded in Puramatrix™ presented morphological features of healthy cells, and some cells exhibited cytoplasmic elongations. Notably, after 21 days in tooth slices containing Puramatrix™, DPSC cells expressed DMP-1 and DSPP, putative markers of odontoblastic differentiation. Significance Collectively, these data suggest that self-assembling peptide hydrogels might be useful injectable scaffolds for stem cell-based Regenerative Endodontics.

Substances dissolved from the adhesive system tested were cytotoxic for human dental pulp fibroblasts in culture, whilst substances leached from calcium hydroxide were biocompatible.

After aggression to the dental pulp, some cells produce cytokines in order to start and control the inflammatory process. Among these cytokines, interleukin-1 beta (IL-1ß) and interleukin-8 (IL-8) emerge as important ones. Objective: The purpose of this study was to analyze the location, distribution and concentration of these cytokines in healthy and inflamed dental pulps. Material and methods: Twenty pulps, obtained from healthy third molars (n=10) and from pulpectomies (n=10) were used for the study, with half of each group used for immunohistochemistry and half for protein extraction and ELISA assays. Fibroblasts obtained from healthy dental pulps, stimulated or not by Escherichia coli lipopolysaccharide (LPS), in order to simulate aggression on the cell cultures, were also used and analyzed by ELISA for IL-1ß and IL-8 as complementary information. Data obtained from immunohistochemistry were qualitatively analyzed. Data obtained from ELISA assays (tissue and cells) were statistically treated by the t-test (p<0.05). Results: Immunohistochemically, it was observed that inflamed pulps were strongly stained for both cytokines in inflammatory cells, while healthy pulps were not immunolabeled. ELISA from tissues quantitatively confirmed the higher presence of both cytokines. Additionally, cultured pulp fibroblasts stimulated by LPS also produce more cytokines than the control cells. Conclusions: It may be concluded that inflamed pulps present higher amounts of IL-1ß and IL-8 than healthy pulps and that pulp fibroblasts stimulated by bacterial LPS produce higher levels of IL-1ß and IL-8 than the control group.

It was concluded that individuals with SB have higher levels of urinary catecholamines.

Poly(D,L-lactide acid, PDLLA) has been researched for scaffolds in bone regeneration. However, its hydrophobocity and smooth surface impedes its interaction with biological fluid and cell adhesion. To alter the surface characteristics, different surface modification techniques have been developed to facilitate biological application. The present study compared two different routes to produce PDLLA/superhydrophilic vertically aligned carbon nanotubes:nanohydroxyapatite (PDLLA/VACNT-O:nHAp) scaffolds. For this, we used electrodeposition and immersion in simulated body fluid (SBF). Characterization by goniometry, scanning electron microscopy, X-ray diffraction, and infrared spectroscopy confirmed the polymer modifications, the in vitro bioactivity, and biomineralization. Differential scanning calorimetry and thermal gravimetric analyses showed that the inclusion of VACNT-O:nHA probably acts as a nucleating agent increasing the crystallization rate in the neat PDLLA without structural alteration. Our results showed the formation of a dense nHAp layer on all scaffolds after 14 days of immersion in SBF solution; the most intense carbonated nHAp peaks observed in the PDLLA/VACNT-O:nHAp samples suggest higher calcium precipitation compared to the PDLLA control. Both cell viability and alkaline phosphatase assays showed favorable results, because no cytotoxic effects were present and all produced scaffolds were able to induce detectable mineralization. Bone defects were used to evaluate the bone regeneration; the confocal Raman and histological results confirmed high potential for bone applications. In vivo study showed that the PDLLA/VACNT-O:nHAp scaffolds mimicked the immature bone and induced bone remodeling. These findings indicate surface improvement and the applicability of this new nanobiomaterial for bone regenerative medicine.

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