The root is crucial for the physiological function of the tooth, and a healthy root allows an artificial crown to function as required clinically. Tooth crown development has been studied intensively during the last f...The root is crucial for the physiological function of the tooth, and a healthy root allows an artificial crown to function as required clinically. Tooth crown development has been studied intensively during the last few decades, but root development remains not well understood. Here we review the root development processes, including cell fate determination, induction of odontoblast and cementoblast differentiation, interaction of root epithelium and mesenchyme, and other molecular mechanisms. This review summarizes our current understanding of the signaling cascades and mechanisms involved in root development. It also sets the stage for de novo tooth regeneration.展开更多
Three-dimensional(3D)-printed scaffolds have attracted considerable attention in recent years as they provide a suitable environment for bone cell tissue regeneration and can be customized in shape.Among many other ch...Three-dimensional(3D)-printed scaffolds have attracted considerable attention in recent years as they provide a suitable environment for bone cell tissue regeneration and can be customized in shape.Among many other challenges,the material composition and geometric structure have major impacts on the performance of scaffolds.Hydroxyapatite and tricalcium phosphate(HA/TCP),as the major constituents of natural bone and teeth,possess attractive biological properties and are widely used in bone scaffold fabrication.Many fabrication methods have been investigated in attempts to achieve HA/TCP scaffolds with microporous structure enabling cell growth and nutrient transport.However,current 3D printing methods can only achieve the fabrication of HA/TCP scaffolds with certain range of microporous structure.To overcome this challenge,we developed a slurry-based microscale mask image projection stereolithography,allowing us to form a HA/TCP-based photocurable suspension with complex geometry including biomimetic features and hierarchical porosity.Here,the curing performance and physical properties of the HA/TCP suspension were investigated,and a circular movement process for the fabrication of highly viscous HA/TCP suspension was developed.Based on these investigations,the scaffold composition was optimized.We determined that a 30 wt%HA/TCP scaffold with biomimetic hierarchical structure exhibited superior mechanical properties and porosity.Cell proliferation was investigated in vitro,and the surgery was conducted in a nude mouse in vivo model of long bone with cranial neural crest cells and bone marrow mesenchymal stem cells.The results showed our 3D-printed HA/TCP scaffold with biomimetic hierarchical structure is biocompatible and has sufficient mechanical strength for surgery.展开更多
Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells(MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and ...Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells(MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair. Here we show that suture MSCs give rise to osteoprogenitors that show active bone morphogenetic protein(BMP) signalling and depend on BMP-mediated Indian hedgehog(IHH) signalling to balance osteogenesis and osteoclastogenesis activity. IHH signalling and receptor activator of nuclear factor kappa-Β ligand(RANKL) may function synergistically to promote the differentiation and resorption activity of osteoclasts. Loss of Bmpr1a in MSCs leads to downregulation of hedgehog(Hh) signalling and diminished cranial sutures. Significantly, activation of Hh signalling partially restores suture morphology in Bmpr1a mutant mice, suggesting the functional importance of BMP-mediated Hh signalling in regulating suture tissue homeostasis. Furthermore, there is an increased number of CD200+ cells in Bmpr1a mutant mice, which may also contribute to the inhibited osteoclast activity in the sutures of mutant mice. Finally, suture MSCs require BMPmediated Hh signalling during the repair of calvarial bone defects after injury. Collectively, our studies reveal the molecular and cellular mechanisms governing cell–cell interactions within the cranial suture that regulate calvarial bone homeostasis and repair.展开更多
Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavio...Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides (HABPs) previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 (ADP5) was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbiditv associated with tooth loss.展开更多
The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research (NI...The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field.展开更多
Cleft palate represents one of the major groups of congenital birth defects in the human population.Despite recent advancements in medical intervention,babies born with cleft palate often suffer multiple handicaps tha...Cleft palate represents one of the major groups of congenital birth defects in the human population.Despite recent advancements in medical intervention,babies born with cleft palate often suffer multiple handicaps that signifi-cantly compromise the quality of their lives.Investigations of craniofacial development and malformations展开更多
基金supported by grants from the NIDCR, NIH (DE012711 and DE014078) to Yang ChaiNational Natural Science Foundation of China (81170943)+1 种基金Beijing Natural Science Foundation (7122051)Funding for Talents in Beijing (D) (2010D003034000012) to Xiao-Feng Huang
文摘The root is crucial for the physiological function of the tooth, and a healthy root allows an artificial crown to function as required clinically. Tooth crown development has been studied intensively during the last few decades, but root development remains not well understood. Here we review the root development processes, including cell fate determination, induction of odontoblast and cementoblast differentiation, interaction of root epithelium and mesenchyme, and other molecular mechanisms. This review summarizes our current understanding of the signaling cascades and mechanisms involved in root development. It also sets the stage for de novo tooth regeneration.
基金supported by the Alfred E.Mann Institute at University of Southern California as a grant to Yang Chai and Yong Chenthe support of National Science Foundation(NSF)grants 1151191 and 1335476the Core Center of Excellence in Nano Imaging(CNI)at USC for the use of microscopic measuring equipment.
文摘Three-dimensional(3D)-printed scaffolds have attracted considerable attention in recent years as they provide a suitable environment for bone cell tissue regeneration and can be customized in shape.Among many other challenges,the material composition and geometric structure have major impacts on the performance of scaffolds.Hydroxyapatite and tricalcium phosphate(HA/TCP),as the major constituents of natural bone and teeth,possess attractive biological properties and are widely used in bone scaffold fabrication.Many fabrication methods have been investigated in attempts to achieve HA/TCP scaffolds with microporous structure enabling cell growth and nutrient transport.However,current 3D printing methods can only achieve the fabrication of HA/TCP scaffolds with certain range of microporous structure.To overcome this challenge,we developed a slurry-based microscale mask image projection stereolithography,allowing us to form a HA/TCP-based photocurable suspension with complex geometry including biomimetic features and hierarchical porosity.Here,the curing performance and physical properties of the HA/TCP suspension were investigated,and a circular movement process for the fabrication of highly viscous HA/TCP suspension was developed.Based on these investigations,the scaffold composition was optimized.We determined that a 30 wt%HA/TCP scaffold with biomimetic hierarchical structure exhibited superior mechanical properties and porosity.Cell proliferation was investigated in vitro,and the surgery was conducted in a nude mouse in vivo model of long bone with cranial neural crest cells and bone marrow mesenchymal stem cells.The results showed our 3D-printed HA/TCP scaffold with biomimetic hierarchical structure is biocompatible and has sufficient mechanical strength for surgery.
基金supported by grants from the National Institute of Dental and Craniofacial Research, NIH (supported by R01 DE026339)
文摘Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells(MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair. Here we show that suture MSCs give rise to osteoprogenitors that show active bone morphogenetic protein(BMP) signalling and depend on BMP-mediated Indian hedgehog(IHH) signalling to balance osteogenesis and osteoclastogenesis activity. IHH signalling and receptor activator of nuclear factor kappa-Β ligand(RANKL) may function synergistically to promote the differentiation and resorption activity of osteoclasts. Loss of Bmpr1a in MSCs leads to downregulation of hedgehog(Hh) signalling and diminished cranial sutures. Significantly, activation of Hh signalling partially restores suture morphology in Bmpr1a mutant mice, suggesting the functional importance of BMP-mediated Hh signalling in regulating suture tissue homeostasis. Furthermore, there is an increased number of CD200+ cells in Bmpr1a mutant mice, which may also contribute to the inhibited osteoclast activity in the sutures of mutant mice. Finally, suture MSCs require BMPmediated Hh signalling during the repair of calvarial bone defects after injury. Collectively, our studies reveal the molecular and cellular mechanisms governing cell–cell interactions within the cranial suture that regulate calvarial bone homeostasis and repair.
基金The research was mainly supported by NSF-MRSEC (DMR# 0520567) at the University of Washington (MG, MH, HF, RS, EEO, CT and MS)by NIH,National Institute of Dental and Craniofacial Research grant DE13045 (MLS)+2 种基金grant DE15109 to MJS (The studies described here were completed while MJS was at the University of Washington)JAH was supported by the University of Washington, Warren G. Magnuson Scholars Awardthe NIH,National Institute of Dental and Craniofacial Research Ruth L. Kirschstein Individual pre-doctoral dental scientist fellowship, 5F30DE01752
文摘Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides (HABPs) previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 (ADP5) was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbiditv associated with tooth loss.
文摘The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field.
基金Supported by the National Institute of Dental and Craniofacial Research, NIH(DE014078, DE012711 and DE017007)March of Dimes Birth Defects Foundation
文摘Cleft palate represents one of the major groups of congenital birth defects in the human population.Despite recent advancements in medical intervention,babies born with cleft palate often suffer multiple handicaps that signifi-cantly compromise the quality of their lives.Investigations of craniofacial development and malformations