Angiogenesis, the formation of new blood vessels, is a fundamental process in both physiological repair mechanisms and pathological conditions, including cancer and chronic inflammation. Hydrogels are commonly used as in vitro models to mimic the extracellular matrix (ECM) and support endothelial cell behavior during angiogenesis. Mesenchymal stem cells further augment cell and tissue growth and are therefore widely used in regenerative medicine. Here we examined the combination of distinct hydrogel types—fibrin, collagen, and human platelet lysate (HPL)—on the formation of capillaries in a co-culture system containing human umbilical vein endothelial cells (HUVECs) and bone marrow-derived mesenchymal stem cells (BM-MSCs). The mechanical properties and structural changes of the hydrogels were characterized through scanning electron microscopy (SEM) and nanoindentation over 10 days. Fibrin and HPL gels sustained complex network formations, with HPL gels promoting even vascular tube formation of up to 10-fold capillary caliber. Collagen gels supported negligible angiogenesis. Our results suggest that HPL gels in combination with MSC-EC co-culture may be employed to obtain robust vascularization in tissue engineering. This study provides a comparative analysis of fibrin, collagen, and HPL hydrogels, focusing on their ability to support angiogenesis under identical conditions. Our findings demonstrate the superior performance of HPL gels in promoting robust vascular structures, highlighting their potential as a versatile tool for in vitro angiogenesis modeling.

The potential of stem cells, for example upper periodontal ligament stem cells from the maxilla (u-PDLSC) and from the mandible (l-PDLSC), adipose-derived mesenchymal stem cells (AD-MSC), and bone marrow-derived mesenchymal stem cells (BM-MSC), with respect to periodontal remodeling and orthodontic treatment is of great importance. In this work, we focus on the comprehensive adaptability of different stem cell types to mechanical forces with the aim to better understanding cell behavior and to refine a new mechanistic approach to investigate periodontal remodeling. We comprehensively analyze stem cells and observe distinct morphological and proliferation changes under compression in dependence on stem cell type. The cell signaling of extracellular signal-regulated kinase (ERK) and protein kinase B, also called AKT, and their respective phosphorylation shows diverse responses to compression. Additionally, vascular endothelial growth factor and hepatocyte growth factor secretion were reduced under mechanical stress in all cell types, with cell-specific variations. Osteoprotegerin secretion was reduced under compression, particularly in u-PDLSC. At least, diverse soluble receptors of NF-kB-ligand secretion patterns among cell types under pressure were observed, providing crucial insights into bone metabolism. These findings offer a deeper understanding of the behavior of mesenchymal stem cells under mechanical stimuli, highlighting their roles in bone remodeling, wound healing, and tissue regeneration in orthodontic and regenerative medicine contexts. Our results underscore the potential of u-PDLSC, l-PDLSC, and AD-MSC in periodontal regeneration, with AD-MSC showing notable resilience under compression, indicating its promising role for further investigation for orthodontic research. While these findings are encouraging, further research is essential to fully comprehend the mechanism of stem cell-based periodontal therapies.

Orthodontic treatments are concomitant with mechanical forces and thereby cause teeth movements. The applied forces are transmitted to the tooth root and the periodontal ligaments which is compressed on one side and tensed up on the other side. Indeed, strong forces can lead to tooth root resorption and the crown-to-tooth ratio is reduced with the potential for significant clinical impact. The cementum, which covers the tooth root, is a thin mineralized tissue of the periodontium that connects the periodontal ligament with the tooth and is build up by cementoblasts. The impact of tension and compression on these cells is investigated in several in vivo and in vitro studies demonstrating differences in protein expression and signaling pathways. In summary, osteogenic marker changes indicate that cyclic tensile forces support whereas static tension inhibits cementogenesis. Furthermore, cementogenesis experiences the same protein expression changes in static conditions as static tension, but cyclic compression leads to the exact opposite of cyclic tension. Consistent with marker expression changes, the singaling pathways of Wnt/ß-catenin and RANKL/OPG show that tissue compression leads to cementum degradation and tension forces to cementogenesis. However, the cementum, and in particular its cementoblasts, remain a research area which should be explored in more detail to understand the underlying mechanism of bone resorption and remodeling after orthodontic treatments.