Stem cells extracted from developing tissues possibly exhibit not only unique but also superior traits against their developed counterparts. Indeed, stem cells from the apical papilla (SCAP); a unique group of dental stem cells related to developing roots have been shown to be a promising tool for regenerative endodontic procedures and regeneration in general. Studies have characterized the phenotypic traits as well as other regenerative potentials of these cells. Specific sub-populations have been highlighted as well as their neurogenic and angiogenic properties. Nevertheless, in light of the previously discussed features and potential applications of SCAP, there is still much to understand and a lot of information to unravel. The current review will discuss the role of specific markers for detection of different functional populations of SCAP; including CD146 and STRO-1, as well as their true multilineage differentiation potential. In particular, the role of the secretome in association with paracrine signaling in inflammatory microenvironments is also tackled. Additionally, the role of SCAP both in vitro and in vivo during regenerative approaches and in response to different growth factors and biologic scaffolds is highlighted. Finally, this review will shed light on current knowledge regarding the clinical translational potential of SCAP and elucidate possible areas for future research applications.

Magnesium (Mg)-based biomaterials hold considerable promise for applications in regenerative medicine. However, the degradation of Mg needs to be reduced to control toxicity caused by its rapid natural corrosion. In the process of developing new Mg alloys with various surface modifications, an efficient assessment of the relevant properties is essential. In the present study, a WE43 Mg alloy with a plasma electrolytic oxidation (PEO)-generated surface was investigated. Surface microstructure, hydrogen gas evolution in immersion tests and cytocompatibility were assessed. In addition, a novel in vitro immunological test using primary human lymphocytes was introduced. On PEO-treated WE43, a larger number of pores and microcracks, as well as increased roughness, were observed compared to untreated WE43. Hydrogen gas evolution after two weeks was reduced by 40.7% through PEO treatment, indicating a significantly reduced corrosion rate. In contrast to untreated WE43, PEO-treated WE43 exhibited excellent cytocompatibility. After incubation for three days, untreated WE43 killed over 90% of lymphocytes while more than 80% of the cells were still vital after incubation with the PEO-treated WE43. PEO-treated WE43 slightly stimulated the activation, proliferation and toxin (perforin and granzyme B) expression of CD8⁺ T cells. This study demonstrates that the combined assessment of corrosion, cytocompatibility and immunological effects on primary human lymphocytes provide a comprehensive and effective procedure for characterizing Mg variants with tailorable degradation and other features. PEO-treated WE43 is a promising candidate for further development as a degradable biomaterial.

Background/Aim: With the demographic change and associated chronic bone loss, the need for cytocompatible bone replacement materials arise in modern medicine. The aim of this in vitro study was to investigate the cytocompatibility of eleven different bone substitute materials and membranes. Materials and Methods: Seven bone substitute materials and four membranes were assessed in vitro. The specimens were tested based on their interaction with MC3T3 pre-osteoblasts, through the utilization of viability, proliferation, and cytotoxicity assays. Cell vitality was evaluated using live-dead staining. Results: Although we found minor differences in cytocompatibility among the assessed materials, all tested materials can be considered as cytocompatible with a viability of more than 70% of the negative control, which indicates the non-toxic range as defined in current, international standards (DIN EN ISO 10993-5:2009, German Institute for Standardization, Berlin, Germany). Direct live-dead staining assays confirmed satisfactory cytocompatibility of all tested membranes. Conclusion: All examined bone substitute materials and membranes were found to be cytocompatible. In order to assess whether the observed minor differences can impact regenerative processes, further in vivo studies need to be conducted.

Objective: Despite numerous existing treatments for keloids, the responses in the clinic have been disappointing, due to either low efficacy or side effects. Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for fibrotic diseases using mesenchymal stem cells; however, no research has yet been reported to scientifically investigate the effect of human dental pulp stem cells (HDPSCs) on the treatment of keloids. The objective is to provide an experimental basis for the application of stem cells in the treatment of keloids. Methods: Human normal fibroblasts (HNFs) and human keloid fibroblasts (HKFs) were cultured alone and in combination with HDPSCs using a transwell cell-contact-independent cell culture system. The effects of HDPSCs on HKFs were tested using a CCK-8 assay, live/dead staining assay, quantitative polymerase chain reaction, Western blot and immunofluorescence microscopy. Results: HDPSCs did not inhibit the proliferation nor the apoptosis of HKFs and HNFs. HDPSCs did, however, inhibit their migration. Furthermore, HDPSCs significantly decreased the expression of profibrotic genes (CTGF, TGF-β1 and TGF-β2) in HKFs and KNFs (p < 0.05), except for CTGF in HNFs. Moreover, HDPSCs suppressed the extracellular matrix (ECM) synthesis in HKFs, as indicated by the decreased expression of collagen I as well as the low levels of hydroxyproline in the cell culture supernatant (p < 0.05). Conclusions: The co-culture of HDPSCs inhibits the migration of HKFs and the expression of pro-fibrotic genes, while promoting the expression of anti-fibrotic genes. HDPSCs’ co-culture also inhibits the synthesis of the extracellular matrix by HKFs, whereas it does not affect the proliferation and apoptosis of HKFs. Therefore, it can be concluded that HDPSCs can themselves be used as a tool for restraining/hindering the initiation or progression of fibrotic tissue.

In an effort to generate titanium surfaces for implants with improved osseointegration, we used direct laser interference patterning (DLIP) to modify the surface of pure titanium grade 4 of four different structures. We assessed in vitro cytoxicity and cell attachment, as well as the viability and proliferation of cells cultured directly on the surfaces. Attachment of the cells to the modified surfaces was comparably good compared to that of cells on grit-blasted and acid-etched reference titanium surfaces. In concordance with this, viability and proliferation of the cells directly cultured on the specimens were similar on all the titanium surfaces, regardless of the laser modification, indicating good cytocompatibility.