Lithiated porous silicon nanowires stimulate periodontal regeneration.

Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/ß-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/ß-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.

Oral stem cells, decoding and mapping the resident cells populations.

The teeth and their supporting tissues provide an easily accessible source of oral stem cells. These different stem cell populations have been extensively studied for their properties, such as high plasticity and clonogenicity, expressing stem cell markers and potency for multilineage differentiation in vitro. Such cells with stem cell properties have been derived and characterised from the dental pulp tissue, the apical papilla region of roots in development, as well as the supporting tissue of periodontal ligament that anchors the tooth within the alveolar socket and the soft gingival tissue. Studying the dental pulp stem cell populations in a continuously growing mouse incisor model, as a traceable in vivo model, enables the researchers to study the properties, origin and behaviour of mesenchymal stem cells. On the other side, the oral mucosa with its remarkable scarless wound healing phenotype, offers a model to study a well-coordinated system of healing because of coordinated actions between epithelial, mesenchymal and immune cells populations. Although described as homogeneous cell populations following their in vitro expansion, the increasing application of approaches that allow tracing of individual cells over time, along with single-cell RNA-sequencing, reveal that different oral stem cells are indeed diverse populations and there is a highly organised map of cell populations according to their location in resident tissues, elucidating diverse stem cell niches within the oral tissues. This review covers the current knowledge of diverse oral stem cells, focusing on the new approaches in studying these cells. These approaches "decode" and "map" the resident cells populations of diverse oral tissues and contribute to a better understanding of the "stem cells niche architecture and interactions. Considering the high accessibility and simplicity in obtaining these diverse stem cells, the new findings offer potential in development of translational tissue engineering approaches and innovative therapeutic solutions.

Future horizons: embedding the evolving science of regenerative dentistry in a modern, sustainable dental curriculum.

Regenerative dentistry is an emerging field promising to revolutionise the way we approach and perform clinical therapies. This multidisciplinary field, integrating cellular biology, material science and tissue engineering, aims to restore and maintain biological vitality unlike conventional dental therapies, providing a new approach in achieving sustainability within dentistry. Although this emerging field in dentistry seems futuristic and a distant reality, it is closer than we perceive it, as rapid scientific advances contribute to novel technologies. In this opinion piece we share our views on the emerging field and the need of embedding the scientific knowledge and sustainability within the dental curriculum. We critically discuss challenges and quests ahead of our dental profession facing the future.

COVID 19 and Dental Education: Transitioning from a Well-established Synchronous Format and Face to Face Teaching to an Asynchronous Format of Dental Clinical Teaching and Learning.

The Covid-19 pandemic made it necessary to adopt and establish complete or partial online delivery of our clinical teaching and learning. We developed an alternative approach with a combination of Problem based Learning asynchronous fora and Teacher-facilitated synchronous online discussions. Our aim is to share our educational practice and highlight the requirements and constraints, advantages and challenges of such an approach. It allowed a more student-centred experience, but clinical simulation and face-to-face patient care remain necessary. The Covid-19 pandemic has changed the landscape of dental education for the foreseeable future, with a reduced number of patients in dental clinics. Further study is therefore necessary to understand the lived experience of students and teachers to the adopted online teaching and learning approach.

Stem Cells in Tooth Development, Growth, Repair, and Regeneration.

Human teeth contain stem cells in all their mesenchymal-derived tissues, which include the pulp, periodontal ligament, and developing roots, in addition to the support tissues such as the alveolar bone. The precise roles of these cells remain poorly understood and most likely involve tissue repair mechanisms but their relative ease of harvesting makes teeth a valuable potential source of mesenchymal stem cells (MSCs) for therapeutic use. These dental MSC populations all appear to have the same developmental origins, being derived from cranial neural crest cells, a population of embryonic stem cells with multipotential properties. In rodents, the incisor teeth grow continuously throughout life, a feature that requires populations of continuously active mesenchymal and epithelial stem cells. The discrete locations of these stem cells in the incisor have rendered them amenable for study and much is being learnt about the general properties of these stem cells for the incisor as a model system. The incisor MSCs appear to be a heterogeneous population consisting of cells from different neural crest-derived tissues. The epithelial stem cells can be traced directly back in development to a Sox10(+) population present at the time of tooth initiation. In this review, we describe the basic biology of dental stem cells, their functions, and potential clinical uses.

PKA regulatory subunit expression in tooth development.

Protein kinase A (PKA) plays critical roles in many biological processes including cell proliferation, cell differentiation, cellular metabolism and gene regulation. Mutation in PKA regulatory subunit, PRKAR1A has previously been identified in odontogenic myxomas, but it is unclear whether PKA is involved in tooth development. The aim of the present study was to assess the expression of alpha isoforms of PKA regulatory subunit (Prkar1a and Prkar2a) in mouse and human odontogenesis by in situ hybridization. PRKAR1A and PRKAR2A mRNA transcription was further confirmed in a human deciduous germ by qRT-PCR. Mouse Prkar1a and human PRKAR2A exhibited a dynamic spatio-temporal expression in tooth development, whereas neither human PRKAR1A nor mouse Prkar2a showed their expression in odontogenesis. These isoforms thus showed different expression pattern between human and mouse tooth germs.

In-vitro regulation of odontogenic gene expression in human embryonic tooth cells and SHED cells.

The bud-to-cap stage transition during early tooth development is a time when the tooth-inducing potential becomes restricted to the mesenchyme. Several key genes, expressed in the mesenchyme at this stage, are an absolute requirement for the progression of tooth development. These include the transcription factors Msx1 and Pax9. The inductive potential of tooth mesenchyme cells is a key requisite for whole-tooth bioengineering and thus identification of cells that can retain this property following expansion in culture is an important as yet unresolved, goal. We show here that in-vitro culture of embryonic human tooth mesenchyme cells and SHED cells express low levels of PAX9 and MSX1 and that these levels can be significantly upregulated by activation of different signalling pathways. Such in-vitro manipulation may thus offer a simple way of maintaining/restoring/inducing the odontogenic-inducing capacity in mesenchymal cells.

Stem cell-based biological tooth repair and regeneration.

Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem cells in other parts of the tooth, such as the periodontal ligament and growing roots, play more dynamic roles in tooth function and development. Dental stem cells can be obtained with ease, making them an attractive source of autologous stem cells for use in restoring vital pulp tissue removed because of infection, in regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. As dental stem cells share properties with mesenchymal stem cells, there is also considerable interest in their wider potential to treat disorders involving mesenchymal (or indeed non-mesenchymal) cell derivatives, such as in Parkinson's disease.