Carious lesions are bacteria-caused destructions of the mineralised dental tissues,marked by the simultaneous activation of immune responses and regenerative events within the soft dental pulp tissue.While major molec...Carious lesions are bacteria-caused destructions of the mineralised dental tissues,marked by the simultaneous activation of immune responses and regenerative events within the soft dental pulp tissue.While major molecular players in tooth decay have been uncovered during the past years,a detailed map of the molecular and cellular landscape of the diseased pulp is still missing.In this study we used single-cell RNA sequencing analysis,supplemented with immunostaining,to generate a comprehensive single-cell atlas of the pulp of carious human teeth.Our data demonstrated modifications in the various cell clusters within the pulp of carious teeth,such as immune cells,mesenchymal stem cells(MSC)and fibroblasts,when compared to the pulp of healthy human teeth.Active immune response in the carious pulp tissue is accompanied by specific changes in the fibroblast and MSC clusters.These changes include the upregulation of genes encoding extracellular matrix(ECM)components,including COL1A1 and Fibronectin(FN1),and the enrichment of the fibroblast cluster with myofibroblasts.The incremental changes in the ECM composition of carious pulp tissues were further confirmed by immunostaining analyses.Assessment of the Fibronectin fibres under mechanical strain conditions showed a significant tension reduction in carious pulp tissues,compared to the healthy ones.The present data demonstrate molecular,cellular and biomechanical alterations in the pulp of human carious teeth,indicative of extensive ECM remodelling,reminiscent of fibrosis observed in other organs.This comprehensive atlas of carious human teeth can facilitate future studies of dental pathologies and enable comparative analyses across diseased organs.展开更多
Calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an impro...Calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an improved degradation is essential to match the tissue regeneration, especially in younger patients who are still growing. We demonstrate that a combination of CPC with mesoporous bioactive glass (MBG) particles led to an enhanced degradation in vitro and in a critical alveolar cleft defect in rats. Additionally, to support new bone formation the MBG was functionalized with hypoxia conditioned medium (HCM) derived from rat bone marrow stromal cells. HCM-functionalized scaffolds showed an improved cell proliferation and the highest formation of new bone volume. This highly flexible material system together with the drug delivery capacity is adaptable to patient specific needs and has great potential for clinical translation.展开更多
文摘Carious lesions are bacteria-caused destructions of the mineralised dental tissues,marked by the simultaneous activation of immune responses and regenerative events within the soft dental pulp tissue.While major molecular players in tooth decay have been uncovered during the past years,a detailed map of the molecular and cellular landscape of the diseased pulp is still missing.In this study we used single-cell RNA sequencing analysis,supplemented with immunostaining,to generate a comprehensive single-cell atlas of the pulp of carious human teeth.Our data demonstrated modifications in the various cell clusters within the pulp of carious teeth,such as immune cells,mesenchymal stem cells(MSC)and fibroblasts,when compared to the pulp of healthy human teeth.Active immune response in the carious pulp tissue is accompanied by specific changes in the fibroblast and MSC clusters.These changes include the upregulation of genes encoding extracellular matrix(ECM)components,including COL1A1 and Fibronectin(FN1),and the enrichment of the fibroblast cluster with myofibroblasts.The incremental changes in the ECM composition of carious pulp tissues were further confirmed by immunostaining analyses.Assessment of the Fibronectin fibres under mechanical strain conditions showed a significant tension reduction in carious pulp tissues,compared to the healthy ones.The present data demonstrate molecular,cellular and biomechanical alterations in the pulp of human carious teeth,indicative of extensive ECM remodelling,reminiscent of fibrosis observed in other organs.This comprehensive atlas of carious human teeth can facilitate future studies of dental pathologies and enable comparative analyses across diseased organs.
基金This work was founded by the“AO Trauma Deutschland Nachwuchsf¨orderung”(PK)as well as the German Research Foundation(DFGproject no.449121904)(AL,MG).
文摘Calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an improved degradation is essential to match the tissue regeneration, especially in younger patients who are still growing. We demonstrate that a combination of CPC with mesoporous bioactive glass (MBG) particles led to an enhanced degradation in vitro and in a critical alveolar cleft defect in rats. Additionally, to support new bone formation the MBG was functionalized with hypoxia conditioned medium (HCM) derived from rat bone marrow stromal cells. HCM-functionalized scaffolds showed an improved cell proliferation and the highest formation of new bone volume. This highly flexible material system together with the drug delivery capacity is adaptable to patient specific needs and has great potential for clinical translation.
