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November 22, 2023

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Researchers develop 'game-changing' dental implant technology

by University of California, Los Angeles

A team of UCLA School of Dentistry researchers led by Takahiro Ogawa, D.D.S., Ph.D., has culminated a decade of dental implant research with the development of a cutting-edge technology that ensures near-perfect osseointegration, faster healing times, and significantly reduced complications for patients.

A device blasting one minute of ultraviolet (UV) light treatment on titanium implants —done chairside immediately prior to an implant procedure—has recently come to market and holds opportunities for applications beyond dentistry.

"We have entered a new era in dental implantology," said Dr. Ogawa. "This UV technology not only enhances the effectiveness of dental implants but also improves the quality of life for patients. The possibilities are limitless, and I am incredibly excited about the potential impact on oral and overall health."

Dr. Ogawa and colleagues in the Weintraub Center for Reconstructive Biotechnology team identified a key obstacle in the advancement of dental implant science, which had stagnated for three decades: A layer of hydrocarbons naturally deposited on implant surfaces called titanium pellicle, hindering the integration process. This is also associated with significant post-op complications, with peri-implantitis (gum disease around implants) occurring in 35%–40% of patients.

In response, the team developed a method to remove these hydrocarbons via UV light, which took 48 hours in early trials. Researchers gradually reduced UV treatment times to 12 minutes, but performing the procedure chair-side just before implant surgery only became feasible with their one-minute hydrocarbon removal breakthrough in late 2022. The process is chronicled in an article published in the Journal of Functional Biomaterials , authored by Dr. Ogawa and his team.

The impact of this technology is profound. UV-treated implants exhibit nearly 100% bone integration, doubling their anchoring capability and reducing bacterial susceptibility by 60% compared to untreated control implants. This means faster healing, lower risk of complications, and increased suitability for a larger portion of the patient population, including aging patients, smokers, and those with diabetes and osteoporosis among other conditions.

A follow-up journal article in which Dr. Ogawa is the primary author, published Oct. 29 in Cells , demonstrates how one-minute UV treatment induces unprecedented action of gingival (gum) cells to seal the implants, limiting bacterial invasion and reducing incidents of peri-implantitis.

"Our goal is to eradicate peri-implantitis," said Dr. Ogawa.

Additionally, the technology allows for more versatile occlusion, eliminating the need for smaller implant crowns and reducing the number of required bridge implants.

Dr. Ogawa is energized by the potential use of UV-treated implants in the broader medical world.

"Orthopedic implants like hip joint reconstruction and spine fixation show a high incidence of revision surgery and complications. I believe UV-treated implants will help mitigate them," he said.

Toshikatsu Suzumura et al, Vacuum Ultraviolet (VUV) Light Photofunctionalization to Induce Human Oral Fibroblast Transmigration on Zirconia, Cells (2023). DOI: 10.3390/cells12212542

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• World J Stem Cells
• v.15(3); 2023 Mar 26
• PMC10052340

Clinical trials using dental stem cells: 2022 update

Wen-peng song.

Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

Lu-Yuan Jin

Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China

Meng-Di Zhu

Deng-sheng xia.

Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China. nc.ude.umcc.liam@aixsd

Supported by the National Natural Science Foundation of China, No. 82071073 and No. 82270951 .

Corresponding author: Deng-Sheng Xia, DDS, Assistant Professor, Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, No. 4 Tiantan Xili, Dongcheng District, Beijing 100050, China. nc.ude.umcc.liam@aixsd

For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.

Core Tip: Since dental pulp stem cells were first isolated and identified in 2000, a variety of dental stem cells (DSCs) have been reported. DSCs have shown satisfactory clinical effects in the treatment of a variety of diseases and have great potential for clinical application. This paper will summarize DSC-based clinical trials and put forward the current limitations and perspectives to accelerate and extend the clinical application of DSCs.

INTRODUCTION

Mesenchymal stem cells (MSCs) are a population of unspecialized cells characterized by the properties of self-renewal and multidirectional differentiation[ 1 , 2 ]. Currently, MSCs are currently being explored for the treatment of many diseases, such as cardiovascular disease, neurodegenerative diseases, dental diseases, and metabolic diseases[ 1 ].

Dental SCs (DSCs) were reported to have similar features to MSCs[ 3 ]. Since dental pulp SCs (DPSCs) were first successfully isolated from the extracted third molar in 2000[ 4 ], multiple DSC types have been harvested from mature and immature teeth and their surrounding tissues, including periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAP), stem cells from exfoliated deciduous teeth (SHED), gingiva-derived mesenchymal SCs (GMSCs), and dental follicle progenitor cells (DFPCs)[ 5 - 7 ] (Figure ​ (Figure1). 1 ). DSCs develop from the neural crest and express both stem cell markers and neural markers[ 8 , 9 ]. It was reported that DSCs have the potential for multipotent differentiation into osteogenic, chondrogenic, adipogenic, neurogenic, odontogenic, dentinogenic cells, and so on[ 10 ]. In addition to their self-renewal and differentiation properties, DSCs have also been reported to be involved in secretion, immunomodulation, and tumor processes[ 3 , 11 ]. Based on the characteristics of DSCs, many clinical articles and clinical trials have used DSCs in tissue regeneration and the treatment of various diseases, such as pulpitis, periapical lesions, and periodontitis[ 12 ].

Tissue origin, harvest, characteristics, and clinical application potential of the various populations of dental stem cells. Dental pulp stem cells and stem cells from exfoliated deciduous teeth can be isolated from the inner dental pulp of permanent teeth and deciduous exfoliated teeth, respectively. Stem cells from apical papilla can be extracted from the apical papilla; periodontal ligament stem cells can be harvested from the periodontal ligament; and dietary fiber supplementation combinations can be derived from the dental follicle. Gingiva-derived mesenchymal stem cells can be extracted from gingiva. Citation: Sharpe PT. Dental mesenchymal stem cells. Development 2016; 143: 2273-2280[ 139 ]. Copyright ©The Authors 2016. Published by The Company of Biologists Ltd. The authors have obtained the permission for figure using from the Company of Biologists Ltd ( Supplementary material ).

In this study, the current status of clinical articles and clinical trials using DSCs in the treatment of various diseases and conditions are reviewed. In addition, current limitations and perspectives, including harvesting DSCs from inflamed tissue, applying DSC-conditioned medium (CM) and DSC-derived extracellular vesicles (EVs), and expanding-free strategies, are also discussed.

CHARACTERISTICS OF DSCS

Based on their various sources, DSCs are divided into DPSCs, SHED, PDLSCs, SCAP, GMSCs, and DFPSCs (Figure ​ (Figure1). 1 ). DSCs are known to express not only mesenchymal and embryonic stem cell markers (such as CD44, STRO-1, and Nanog) but also neuronal markers because they originate from embryonic neural crests[ 8 , 9 ] (Table ​ (Table1). 1 ). However, they do not express CD34, CD45, or CD11b, which are defined as hematopoietic markers[ 7 ].

Characteristics of different types of dental stem cells

ALP: Alkaline phosphatase; CD: Cluster of differentiation; CNPase: 2’,3’-cyclic nucleotide 3’-phosphodiesterase; GAD: Glutamic acid decarboxylase; GFAP: Glial fibrillary acidic protein; MAP-2: Microtubule associated protein 2; NeuN: Neuronal nuclei; NFM: Neurofilament medium chain; NGFR: Nerve growth factor receptor; NSE: Neuron-specific enolase; OCT: Octamer-binding transcription factor; PAX-6: Paired Box 6; PSA-NCAM: Polysialylated neural cell adhesion molecule; REX-1: RNA exonuclease 1 homolog; SOX: Sex determining region Y-box; SSEA: Stage-specific embryonic antigen; TH: Tyrosine hydroxylase; SHED: Stem cells from exfoliated deciduous teeth.

Similar to mesenchymal stem cells, DSCs showed the ability of self-renewal and multidirectional differentiation, such as osteogenic, chondrogenic, adipogenic, neurogenic, odontogenic, dentinogenic, cementogenic, and myogenic differentiation[ 13 - 16 ] (Table ​ (Table1). 1 ). In addition, even in the undifferentiated state, DSCs were able to secrete several angiogenic and neurotrophic factors, including vascular endothelial growth factor (VEGF), ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), glia-derived neurotrophic factor (GDNF), and β-nerve growth factor (β-NGF), to promote angiogenesis and tissue regeneration[ 17 , 18 ].

In addition, the immunomodulatory features of DSCs have also been the focus of a number of studies. First, it was reported that DSCs, like mesenchymal stem cells, faintly express the MHC class II antigen HLA-DR and maintain low immunogenicity[ 19 - 21 ]. Second, local tissue regeneration and inflammation could be influenced by the secretome of DSCs (including the production of inflammatory and anti-inflammatory cytokines and the regulation of immune cells), which is also regulated by the local inflammatory microenvironment[ 21 - 24 ]. Finally, the inflammatory microenvironment could impact the behaviors of DSCs, such as proliferation potential, migration, homing, and differentiation[ 22 ].

Based on the characteristics of DSCs, they have been widely studied in regenerative medicine and tissue engineering and have shown an amazing therapeutic effect on oral-facial, neurologic, corneal, cardiovascular, hepatic, diabetic, renal, muscular, tenogenic, dystrophic and autoimmune conditions in both animal and human models[ 21 , 25 - 27 ]. For example, the proliferation, paracrine effect, and multidirectional differentiation potential of DSCs support the application of DSCs in regenerative medicine ( e.g. , dental pulp and bone tissue regeneration)[ 28 , 29 ]. The anti-inflammatory, immunomodulatory, and immunoevasive properties of DSCs also help in the treatment of plaque psoriasis[ 30 ] (Figure ​ (Figure1). 1 ). DSC-based therapies have broad prospects for clinical application.

It is worth noting that the naming of mesenchymal stem cells and mesenchymal stromal cells remains controversial. Based on the position paper issued by The International Society for Cell & Gene Therapy (ISCT) Mesenchymal Stromal Cell (ISCT MSC) in 2005, mesenchymal stem cells are not equivalent or interchangeable with mesenchymal stromal cells[ 31 ]. Mesenchymal stem cells refer to progenitor cell populations with obvious self-renewal and differentiation functions, while mesenchymal stromal cells refer to large populations with significant secretion, immune regulation, and homing properties[ 32 - 34 ]. As we have just summarized, dental stem cells share some of the characteristics of both mesenchymal stem cells and mesenchymal stromal cells, and more consensus articles may be needed to further define the naming of dental stem cells.

DSC-BASED CLINICAL TRIALS FROM PUBLISHED ARTICLES

Pulpitis and pulp necrosis.

Four studies were reported to treat pulp necrosis or irreversible pulpitis using autologous DPSCs or SHED, including a randomized controlled trial (RCT), two case series, and a case report[ 28 , 35 - 37 ] (Table ​ (Table2). 2 ). Xuan et al [ 28 ] applied SHED in the treatment of pulp necrosis caused by trauma and observed dental pulp tissue regeneration at 12 mo and 24 mo after transplantation. Meanwhile, the results also showed increased dental root length and decreased apical foramen width compared with traditional apexification treatment. Two case series reported by Nakashima et al [ 35 , 37 ] indicated that DPSCs transplanted with granulocyte colony-stimulating factor and gelatin sponges could increase pulp sensitivity and mineralization and recover the signal intensity (SI) of regenerated pulp tissue on MRI examination. Meza et al [ 36 ] transplanted DPSCs and leukocyte platelet-rich fibrin (L-PRF) harvested from autologous inflamed dental pulp and blood, respectively, to the root canal of irreversible pulpitis teeth and observed dentin bridge formation and a response to the cold test and electric pulp test.

Dental stem cell-based clinical trials from published articles

BMD: Bone mineral density; CAL: Clinical attachment level; CCT: Controlled clinical trials; COVID-19: Coronavirus disease 2019; DBBM: Deproteinized bovine bone mineral; GR: Gingival recession; G-CSF: Granulocyte colony stimulating factor; HA/TCP: Hydroxyapatite/tricalcium phosphate; IIEF: International index of erectile function; L-PRF: Leukocyte-platelet rich fibrin; MIST: Minimally invasive surgical technique; MRI: Magnetic resonance imaging; PD: Probing depth; PDL: Periodontal ligament; PDLPs: Periodontal ligament progenitor cells; PPD: Periodontal probing depth; PRF: Platelet rich fibrin; PRP: Platelet-rich plasma; PEG-PLGA: Poly (lactide-co glycolide)-polyethylene glycol; RCT: Random clinical trial; rh-BMP: Recombinant human bone morphogenetic protein; SI: Signal intensity; SVF: Stromal vascular fraction: TCP: Tricalcium phosphate; TM: Tooth mobility; VEGF: Vascular endothelial growth factor; SHED-CM: Stem cells from exfoliated deciduous teeth conditioned medium.

Periapical lesions

In a case report and two case series, SCAP/SHED combined with a polyethylene glycol polylactic-polyglycolic acid (PEG-PLGA) scaffold and SHED combined with bioglass were used for the treatment of periapical lesions[ 38 - 40 ] (Table ​ (Table2). 2 ). Periapical tissue healing was found in the follow-up examinations of all three studies. It was reported a positive response in the test of dental pulp activity after SHED transplantation, suggesting the regeneration of pulp or pulp-like tissue, which does not occur in traditional root canal therapy[ 39 , 40 ].

Periodontal intrabony defects

There are two RCTs, a controlled clinical trial (CCT), three case series, and two case reports of DSC-based treatment for periodontal intrabony defects[ 29 , 41 - 46 ] (Table ​ (Table2). 2 ). The RCT of Ferrarotti et al [ 41 ] indicated that pulp micrografts applied with collagen sponges could significantly reduce PD and CAL and promote the regeneration of bone defects when compared with collagen sponges alone. Three case series and a case report using pulp micrografts/DPSCs and collagen sponges also reported similar results of periodontal benefits[ 46 - 49 ]. It was reported a novel approach using periodontal ligament soft tissue, gelatin sponges, and cementum scrapings, which reduced the CAL and PD of periodontitis teeth in their case report[ 45 ].

Although two case series demonstrated the periodontal benefits of PDLPs and PDL-derived cell sheets[ 43 , 44 ], significant differences in periodontal indices (including PD and CAL) were not observed between the test groups and control groups in the other two CCTs that applied PDLSC and PDLSC sheets[ 29 , 42 ]. Several factors might have contributed to the lack of significant differences in the outcomes, such as satisfactory scaffold material properties and small sample sizes. In these four studies, β-TCP, HA/TCP, and deproteinized bovine bone mineral (Bio-oss ® ) were applied as scaffold materials. Although some studies reported abilities to provide support for PDLSCs on osteogenic differentiation of these scaffolds in vitro and in vivo [ 50 - 53 ], only using these scaffolds also achieved great clinical benefits in the treatment of periodontitis[ 54 - 56 ]. The excellent performance of the scaffold may have overshadowed the contribution by PDLSCs. More clinical studies at multiple centers with different amounts and types of DSCs, more follow-up time points, and larger sample sizes are necessary, and the results of such studies would be meaningful.

Bone defects caused by other conditions

In addition to periodontal intrabony defects, DSCs were also used for the treatment of post-extraction sockets, mandibular osteoradionecrosis, bone defects after ameloblastoma resection, and sinus lifting[ 57 - 61 ] (Table ​ (Table2). 2 ). Two split-mouth RCTs reported by Barbier et al [ 57 ] and Cubuk et al [ 62 ] did not find significant differences in BD or interdental septum height between the pulp micrograft + scaffold (collagen matrix/L-PRF) group and the scaffold (collagen matrix/L-PRF) group after implantation into post-extraction sockets. However, in another split-mouth CCT designed for regenerating post-extraction sockets, DPSCs combined with collagen sponges promoted the rate of mineralization, the levels of cortical bone, and the expression of bone morphogenetic protein-2 (BMP-2) and VEGF when compared with collagen sponge treatment alone[ 58 ]. Tanikawa et al [ 63 ] reported a historical control study comparing the effects of SHED, rhBMP, and iliac crest bone grafts in treating cleft lip and palate. The SHED group showed similar satisfactory performance in bone healing compared with iliac crest bone grafts and a higher bone filling percentage compared with the rhBMP group at the 6-mo follow-up[ 63 ].

Two case reports indicated that DPSCs combined with TCP could increase the bone regeneration of bone defects caused by osteoradionecrosis and ameloblastoma[ 59 , 60 ]. A case report by Brunelli et al [ 61 ] demonstrated that pulp micrografts + collagen sponges increased the BD in newly formed bone when applied for sinus lifting.

Other conditions

Koga et al [ 64 ] reported a case series that applied SHED conditioned medium (SHED-CM) to treat erectile dysfunction. In this study, the international index of erectile function (IIEF-5), which is clinically used to screen for erectile function and to assess treatment efficacy, was increased after SHED-CM injection into the corpus cavernosum of erectile dysfunction patients[ 64 ]. A case report indicated that SHED intravenous administrations could decrease the scale of unified Huntington’s disease rating, which is designed to assess clinical performance and capacity in patients with Huntington’s disease[ 65 , 66 ]. Meanwhile, the patient with Huntington’s disease also suffered from preexisting pulmonary nodules, and SHED injection did not result in long-term tropism or homing for the patient’s lung adenocarcinoma[ 65 ]. In a case report by Wang et al [ 30 ], GMSCs were used to treat plaque psoriasis via bolus injection, and they observed fully cleared psoriatic lesions without recurrence.

Three clinical study protocols using DSCs have been published in recent years, including the treatment of acute ischemic stroke, chronic disability after stroke, and COVID-19[ 67 - 69 ].

DSC-BASED CLINICAL TRIALS FROM CLINICAL DATABASES

ClinicalTrials.gov ( https://clinicaltrials.gov/ ) and the International Clinical Trials Registry Platform (ICTRP, https://trialsearch.who.int/ ) were screened for DSC-based clinical trials.

To date, there have been 21 clinical trials registered on ClinicalTrials.gov evaluating the use of DSCs in treating periodontitis (33.3%, 7/21), post-extraction sockets (4.8%, 1/21), edentulous alveolar ridge (4.8%, 1/21), cleft lip and palate (9.5%, 2/21), knee osteoarthritis (4.8%, 1/21), dental pulp necrosis (4.8%, 1/21), liver cirrhosis (4.8%, 1/21), type 1 diabetes (4.8%, 1/21), acute ischemic stroke (4.8%, 1/21), Huntington’s disease (14.3%, 3/21), and COVID-19 (9.5%, 2/21) (Table ​ (Table3). 3 ). In addition to the 6 studies reported in ClinicalTrials.gov, 7 clinical trials were registered on the ICTRP using DSCs in the treatment of periodontitis (57.1%, 4/7), wrinkles (28.6%, 2/7), and hair loss (14.3%, 1/7) (Table ​ (Table4). 4 ). In all, 28 clinical trials were registered on these two platforms.

Dental stem cell-based clinical trials registered at clinicaltrials.gov

DBBM: Deproteinized bovine bone mineral; GFs: Gingival fibroblast; PRF: Platelet-rich fibrin; TCP: Tricalcium phosphate; DPSCs: Dental pulp stem cells; SHED: Stem cells from exfoliated deciduous teeth.

Dental stem cell-based clinical trials registered on the International Clinical Trials Registry Platform

DPSCs: Dental pulp stem cells; SHED-CM: Stem cells from exfoliated deciduous teeth conditioned medium.

Several registered clinical trials applied two stages in one work. The most frequently appearing trial phases were phase 1 (42.9%, 12/28), followed by phase 2 (25%, 7/28), Phase 3 (7.1%, 2/28), and Phase 0 (3.6%, 1/28). There were 10 trials (35.7%) in which the phase design was not applied or not selected. One clinical trial reported the outcomes both on the registry platform and in a published article[ 63 ] ( {"type":"clinical-trial","attrs":{"text":"NCT01932164","term_id":"NCT01932164"}} NCT01932164 ), and the published articles of seven trials stated the registered ID[ 29 , 42 , 62 , 63 , 67 , 69 - 71 ], while other trials did not publish any data.

Consistent with the literature, the proportion of clinical trials using DSCs to treat periodontitis was the highest. Eleven registered clinical trials researched the effect of DSCs on periodontitis (39.3%, 11/28). In these trials, various amounts, types, and injection times of DSCs and different application modes (such as DSCs, micrografts, cell sheet pellets, and cell sheet fragments) were applied. In addition, several scaffolds were used in combination with DSCs, including collagen sponges, deproteinized bovine bone minerals, β-TCP scaffolds, and hydroxyapatite-collagen scaffolds.

SAFETY ISSUES REGARDING DSC-BASED THERAPY

Although encouraging treatment effects on diseases have been achieved, the safety issues of stem cell-based therapy remain controversial, especially in long-term follow-up[ 72 ]. At present, the limitations of stem cell-based therapy are mainly focused on non-directional differentiation, accelerating tumor progression.

In addition, uncontrolled non-directional differentiation may have a great impact on the safety of stem cell transplantation. Breitbach et al [ 73 ] found that the encapsulated structures in the infarcted areas contained calcifications and/or ossifications in myocardial infarction mice after MSC injection. In another study, unselected bone marrow cells injected directly induced significant intramyocardial calcification in acutely infarcted myocardium[ 74 ].

Similar to the regeneration of damaged tissue, tumors exert chemotactic effects on MSCs, affecting their recruitment to tumor sites[ 75 - 77 ]. Current studies have shown that MSCs have bidirectional, anti-cancer and pro-cancer, regulatory effects, which raises safety concerns for clinical application. On the one hand, MSCs are the major component of the tumor microenvironment and can be reprogrammed to the pro-tumorigenic phenotype by the tumor[ 78 ]. MSCs have been revealed to participate in the initiation, development, progression, and metastasis of multiple cancers[ 79 ]. The pro-cancer effect of stem cells may be achieved by secreting molecules that affect the phenotype of tumor cells, promoting tumor angiogenesis, cancer-associated fibroblast differentiation, cell-to-cell contact, or cell engulfment[ 76 ]. In recent studies, DPSCs and their conditioned medium were reported to promote the proliferation and carcinogenic properties of prostate cancer, oral cancer, breast cancer, and melanoma cells in vitro [ 80 - 82 ].

On the other hand, there is also evidence that MSCs can inhibit the growth of a variety of tumors, including breast cancer, Kaposi’s sarcoma, hepatoma, glioma, and melanoma[ 76 , 83 - 85 ]. DPSCs and their conditioned medium also showed a suppressive effect on the development and migration of colorectal cancer cells through mitogen-activated protein kinase pathways[ 86 ]. In fact, there are few reports of primary pulp malignancies[ 87 ]. In a genome-wide RNA-seq study, phosphatase and tensin homolog (PTEN) expression in DPSCs was higher than that in BMSCs[ 88 ]. PTEN, a phosphatase, can metabolize phosphatidylinositol 3,4,5-triphosphate and directly oppose the activation of the oncogenic PI3K/AKT/mTOR signaling network[ 89 ]. At present, the regulatory effects of stem cells on cancer are still controversial, and the difference in results may be related to cell lines, cell doses, animal models, cancer types, treatment duration time, and other factors.

In conclusion, no adverse events were reported in the published clinical articles or clinical trials using DSCs, which suggested the safety of DSC-based therapy. However, based on current concerns about the safety of stem cell therapy, more in vivo studies on the safety of DSC-based therapies are of great significance.

CURRENT LIMITATIONS AND PERSPECTIVES

Harvesting dscs from inflamed tissue.

Most studies applied stem cells extracted from healthy dental tissue for treatment, but additional surgery (such as third molar extraction) might increase patient suffering. Harvesting stem cells from inflamed dental tissue could be an alternative method, although stem cell abilities might be affected[ 36 , 90 , 91 ].

Several studies have researched the different biological properties of DPSCs derived from normal and inflamed pulps (iDPSCs), and the results are still in dispute[ 92 - 98 ]. In some studies, DPSCs showed better self-renewal ability[ 92 , 93 ] and multidirectional differentiation capacities than iDPSCs[ 92 ], while in other studies, no significant difference was observed[ 94 , 95 , 98 ]. A study by Nie et al [ 97 ] indicated that DPSCs showed higher colony-forming, proliferative, and osteo/dentinogenesis abilities, while iDPSCs demonstrated enhanced chondrogenesis, neurogenesis, angiogenesis, and adipogenesis capacities. Park et al [ 96 ] reported that iDPSCs appear to have higher osteogenic differentiation potential and lower neurogenic differentiation potential than DPSCs.

Differences in inflammation levels may explain the discrepancy in the biological properties of DPSCs and iDPSCs in various studies. Intense and rapid inflammatory stimulation irreversibly initiates pulp necrosis, while low insult levels of inflammation are able to cause reversible pulpitis and promote dentine regeneration[ 99 ]. DPSCs are a suitable source of stem cells for pulp nerve regeneration because of their neuronal differentiation potential. It was reported that acute inflammation with a high level of proinflammatory cytokines could reduce neural precursor cell (NPC) survival and inhibit the neuronal differentiation of NPCs, while chronic inflammation expressed a potentially neuroprotective phenotype and supported neuronal differentiation[ 100 ]. Meanwhile, age, sex, tooth position, and sample size are also confounding factors affecting the function of DPSCs, which should be considered in subsequent studies and clinical practice.

DSC-CM and DSC-EVs

The culture medium collected from cells in culture is known as CM. CM is applied as an alternative therapy for tissue regeneration, which is a less ethical issue because it uses cells indirectly. Koga et al [ 64 ] applied SHED-CM in the treatment of erectile dysfunction, which is the only record of its clinical use to the best of our knowledge.

DSC-CM contains a variety of cytokines associated with vascular and nerve tissue regeneration, such as VEGF, BDNF, β-NGF, GDNF and neurotrophin-3 (NT-3)[ 101 , 102 ]. To date, DSC-CM has been reported to have the potential to promote bone regeneration[ 103 ], periodontal regeneration[ 104 ], angiogenesis[ 105 ], pulp regeneration[ 106 ], and nerve protection/regeneration[ 105 , 107 - 109 ] with great possibilities for clinical application.

In addition, DSC-CM showed satisfactory anti-inflammatory and immunoregulatory effects. Several in vivo studies based on various animal models reported that intravenous injection or intranasal administration of SHED-CM improved liver fibrosis[ 110 ], acute liver failure[ 111 ], acute lung injury[ 112 ], Alzheimer’s disease, temporomandibular joint osteoarthritis[ 113 ], Sjögren’s syndrome[ 114 ], and rheumatoid arthritis[ 115 ] by exerting anti-inflammatory effects. Meanwhile, studies have also reported the effect of SHED-CM on promoting Treg cell differentiation[ 114 ] and M2-like macrophage induction[ 111 , 112 ], as well as inhibiting Th17 cell differentiation[ 114 ] and inflammatory macrophage activation[ 116 ].

In addition to DSC-CM, DSC-EVs harvested from cell-culture medium have also been deeply studied in recent years. Multiple studies have indicated the promotion effect of DSC-EVs on jawbone and calvarial bone regeneration[ 117 , 118 ], angiogenesis and cutaneous wound healing in vivo [ 119 , 120 ]. Li et al [ 121 ] also reported that DSC-EVs could alleviate cerebral ischemia-reperfusion by suppressing the inflammatory response, which is related to the inhibition of the HMGB1/TLR4/MyD88/NF-κB pathway.

The poor survival rate of implanted DSCs and host immunogenic reactions are the main drawbacks of applying DSCs directly. In some comparative studies, stem cell-derived CM showed similar and even better treatment effects on acute lung injury, Parkinsonism, and type 1 diabetes than the direct use of stem cells[ 112 , 122 , 123 ]. DSC-CM and its components (such as EVs) provide several key advantages over cell-based applications, including avoiding the risk of host immunogenic reactions, cost-effectiveness, long-term storage capacity, and simpler evaluation of safety and efficacy[ 104 , 124 ]. Accumulating evidence indicates the great potential of DSC-CM/DSC-EV-based treatment in clinical applications.

Expanding-free strategy

Despite encouraging results of differentiation and tissue regeneration, DSCs still require rigorous cell-expanding procedures to obtain a sufficient number of cells for treatment, which is costly with great technique sensitivity, often taking tens of days. The ex vivo expansion of stem cells often reduces their self-renewal and proliferation abilities[ 125 ]. Direct mechanical digestion or tissue transplantation are promising solutions to these limitations.

In recent years, using mechanical disaggregation of dental tissues instead of cell-expending procedures was successful for harvesting autologous pulp micrografts rich in progenitor cells[ 41 , 126 ]. In 2016, Monti et al [ 126 ] indicated that DSCs harvested by mechanical digestion (Rigenera ® system, HBW, Turin, Italy) were fully comparable to stem cells obtained after enzymatic digestion. In this study, mechanical digestion-obtained DPSCs showed osteogenic, adipogenic, and chondrogenic differentiation abilities in vitro and were able to increase the regeneration of post-extraction sockets in vivo when applied with the collagen sponge[ 126 ].

Pulp micrografts harvested by mechanical digestion were also applied in the treatment of sinus lifting, post-extraction sockets, and periodontal intrabony defects[ 46 , 47 , 49 , 57 , 61 , 62 ]. One clinical trial using pulp micrografts was also designed for periodontitis management ( {"type":"clinical-trial","attrs":{"text":"NCT03386877","term_id":"NCT03386877"}} NCT03386877 ), but the outcome was not reported. Different systems of mechanical disaggregation were applied in these studies, including BD Medimachine (BD Biosciences San Jose, CA, United States)[ 62 ], the Rigenera ® system (HBW, Turin, Italy)[ 46 , 57 , 61 ], and the Medimachine System (Consul TS, Orbassano, Italy)[ 47 , 49 ]. In brief, dental pulp is first collected from extracted teeth and then sent to the mechanical disaggregation system to obtain pulp micrografts. After filtration or without filtration, pulp micrografts are combined with the scaffold for transplantation.

In addition, Vandana et al [ 125 ] described a novel approach using stem cell assistance in the periodontal regeneration technique (SAI-PRT), which contained periodontal ligament soft tissue gelatin sponge scaffolds and cementum scrapings. In their research, SAI-PRT successfully bypassed in vitro culture and expanded PDLSCs, resulting in satisfactory defect filling of periodontal intrabony defects[ 125 ].

Embryonic stem cells, PSCs, and DSCs

Embryonic stem cells (ESCs) are pluripotent cells of great significance to developmental biology. They give rise to all types of germ layer cells in the embryo. The self-renewal ability and plasticity of ESCs make it possible to generate unlimited numbers of different types of cells in vitro [ 127 ]. Similar to embryonic cells, PSCs derived from different somatic cells also have the ability to immortalize and differentiate into the three germ layers[ 128 ]. The properties of these two cell types make them promising sources for stem cell-based therapy for various diseases and injuries. However, due to the limitations of ESCs and PSCs, adult stem cells (such as DSCs) still possess high application value.

First, ethical issues regarding the use of ESCs make their clinical application challenging[ 128 ]. Second, the preparation of autologous PSCs takes a long time (more than 3 mo) and has high medical cost, and the immune rejection issue of allotransplantation should be considered[ 129 ]. In addition, teratomas are germ cell tumors containing cells of two or three germ lines that always occur via uncontrollable stem cell proliferation and differentiation[ 130 , 131 ]. In experimental studies, stem cell transplants (especially ESC and PSC transplants) have been found to increase the risk of teratomas, raising safety concerns[ 131 - 133 ]. Previously, viral vector integration and contamination of animal-derived components also posed obstacles to the use of PSCs, but these problems have been addressed by innovative techniques, such as integration-free methods and xeno-free culture[ 134 - 136 ].

DSCs did not show unlimited proliferation potential and demonstrated poorer differentiation ability than PSCs and ESCs[ 137 ]. However, the advantages of DSCs over ESCs and PSCs, such as fewer ethical issues and lower teratoma risk[ 87 , 88 , 138 ], lower cost and shorter preparation period, harvesting from medical waste, and implementing therapeutic effects without gene editing, grant them greater potential for clinical applications in the future.

Many clinical articles and clinical trials of autologous and allogeneic DSCs have aimed to evaluate their therapeutic effects on various diseases, such as pulpitis, periapical lesions, periodontitis, cleft lip and palate and Huntington’s disease. In most studies, satisfactory clinical treatment results were obtained, while clinical benefits of using DSCs were not found in some research. Although safety risks exist for stem cell-based therapies, safety issues have not been reported in the clinical applications of DSCs. In the future, in addition to continuing to study the efficacy and safety of DSC-based treatment, harvesting DSCs from inflammatory tissues, expanding-free strategies, and applying DSC-CM or DSC-EVs should be studied, as they have strong research value and application potential. Taken together, DSC-based therapy is a promising tool for the treatment of various diseases and can be further promoted.

ACKNOWLEDGEMENTS

We thank our friend Han-Yi Dong for designing and drawing Figure ​ Figure1 1 .

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Peer-review started: December 5, 2022

First decision: January 11, 2023

Article in press: March 8, 2023

Specialty type: Dentistry, oral surgery and medicine

Country/Territory of origin: China

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): C, C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Collart-Dutilleul PY, France; Ventura C, Italy S-Editor: Chen YL L-Editor: A P-Editor: Chen YL

Contributor Information

Wen-Peng Song, Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Lu-Yuan Jin, Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.

Meng-Di Zhu, Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.

Hao Wang, Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Deng-Sheng Xia, Department of General Dentistry and Integrated Emergency Dental Care, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China. nc.ude.umcc.liam@aixsd .

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Digitalization, technologies, new approaches, and telemedicine in dentistry and craniofacial/temporomandibular disorders.

Conflicts of Interest

• Alqahtani, J.; Alhemaid, G.; Alqahtani, H.; Abughandar, A.; AlSaadi, R.; Algarni, I.; AlSharif, W.; Al-Harbi, S.; Burwaih, R.; Hasan, A.; et al. Digital Diagnostics and Orthodontic Practice. J. Healthc. Sci. 2022 , 2 , 112–117. [ Google Scholar ] [ CrossRef ]
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Share and Cite

Franco, R.; Minervini, G. Digitalization, Technologies, New Approaches, and Telemedicine in Dentistry and Craniofacial/Temporomandibular Disorders. Appl. Sci. 2024 , 14 , 5871. https://doi.org/10.3390/app14135871

Franco R, Minervini G. Digitalization, Technologies, New Approaches, and Telemedicine in Dentistry and Craniofacial/Temporomandibular Disorders. Applied Sciences . 2024; 14(13):5871. https://doi.org/10.3390/app14135871

Franco, Rocco, and Giuseppe Minervini. 2024. "Digitalization, Technologies, New Approaches, and Telemedicine in Dentistry and Craniofacial/Temporomandibular Disorders" Applied Sciences 14, no. 13: 5871. https://doi.org/10.3390/app14135871

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The next revolution in dental care is about to begin

From fluoride toothpaste to dental sealants, science has brought all sorts of tools for fighting tooth decay — and yet 91% of Americans between 20 and 64 years of age are affected by dental caries.

But provocative new research suggests that cell-stimulating medications can “trick” teeth into repairing themselves. If these “small molecule” drugs work as well as scientists think they will, we may be on the cusp of a new era in which dental tissue and even entire teeth can be regrown .

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When decay reaches the pulp, dentists perform a root canal. This involves removing the bulk of the tooth and then filling what’s left with amalgam. The tooth is then sealed with an artificial cap, but this can fail over time as a result of the stresses of chewing.

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The holy grail for dental researchers is the ability to regrow an entire missing tooth. Sharpe has done this in mice, but doing the same in humans raises ethical and legal concerns. It would involve the creation of a so-called tooth primordium (a tooth in its earliest stage of development) and implanting it in the jaw where the missing tooth had been. To create a tooth primordium, it’s necessary to harvest stem cells from human embryos — which bumps up against U.S. law .

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A dental crown, also sometimes referred to as a “cap,” is a type of dental restoration that fits over the remains of a tooth to restore the appearance of the natural tooth or to protect it from further damage.

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by Mary Beth Versaci

June 12, 2022

Original Article

Pathways to dentistry: Researchers move dental profession forward

Contributions have lasting impact on oral health care.

Editor's note: This is the third article in a series that celebrates the diversity of career paths in dentistry and the Association's efforts in supporting dentists' career choices in the profession.

From examining the connections between oral and overall health to evaluating the behavior of materials used in dentistry, researchers ask the questions and do the work to inform how dentists care for their patients every day.

"Dentistry is an amazing profession that has offered so many of us the opportunity to improve patients' lives. It is critical that we continue to evolve and expand our understanding of the diseases and conditions that affect our patients and continue to work to optimize the treatments that they receive," said Mia Geisinger, D.D.S., professor and director of the Advanced Education Program in Periodontology at the University of Alabama at Birmingham School of Dentistry. "My goal in research is always to change the way that we treat patients for the better, and while the pace of scientific discovery may be incremental, we continually strive to improve oral and overall health for all."

The American Dental Association recognizes the importance of research — like Dr. Geisinger's on the impact of periodontal disease and treatment on overall health — to the practice of dentistry. One of its core values is to be a science- and evidence-based organization, a goal that is supported by the ADA Science & Research Institute, which conducts research and produces evidence-based resources for dentists.

"Scientific research is so important to the health and advancement of the dental profession. That's why I'm really proud of the work ADASRI does," said Marcelo Araujo, D.D.S., Ph.D., chief science officer of the ADA and CEO of ADASRI. "At ADASRI, our work runs the gamut of scientific research — everything from basic science, like the creation of novel dental materials, to applied science that tests and refines dental materials, to clinical and translational research that communicates that basic and applied science in a way that is easy to implement chairside. As a whole, the work of ADASRI’s researchers, and really the work of all dental researchers, has a profound impact on improving dentistry."

The ADA also has two scientific journals: The Journal of the American Dental Association and JADA Foundational Science.

"The ADA continues to demonstrate its strong commitment to the health sciences through many avenues, including the dissemination of basic, translational and clinical research through its journals and other media offerings," said Jack L. Ferracane, Ph.D., editor-in-chief of JADA Foundational Science. "It all boils down to creating new and better pathways to oral health, and we all find it exciting and gratifying to play our different roles in the process that links discovery to successful clinical care."

A New Day for Dentistry, a campaign launched by ADA President Cesar R. Sabates, D.D.S., celebrates the ADA’s diverse community of dentists by recognizing their personal differences and the varied career paths they have chosen within the profession.

"Researchers are essential members of the dental workforce," Dr. Sabates said. "Clinicians strive to provide the best care they can to their patients, and researchers provide the evidence they need to make informed decisions. Their work also helps to expand dentistry’s knowledge base, driving innovation and advancement in our profession. The contributions of researchers have a lasting impact on all facets of oral health care."

For dentists who choose to pursue research as part of their career, a natural curiosity is key.

"I was exposed to research and science when I was in high school, and ever since, I was always interested in learning the underlying mechanisms of diseases," said Hatice Hasturk, D.D.S., Ph.D., director of the Center for Clinical and Translational Research and senior member of the staff at the Forsyth Institute. "I believe that without knowing what is really involved in tissues or structures we are working with, we cannot provide an effective and long-lasting solution."

Dr. Hasturk, who won the ADA’s 2020-21 Norton M. Ross Award for Excellence in Clinical Research and serves on the ADA Council on Scientific Affairs, teaches at the Boston University Henry M. Goldman School of Dental Medicine and Harvard School of Dental Medicine and practices once a week as a staff dentist/periodontist at the Forsyth Faculty Associates Clinic. Her research focuses on periodontology and immunology.

Dr. Hasturk's studies have shown that changing the body's response to infections and diseases can reduce the oral disease it is experiencing, provide better stability and lead the body to produce more beneficial molecules that can help improve its defense system against other infections and diseases.

"As a dentist/periodontist, my goal is to provide the best prevention and best treatment to my patients," Dr. Hasturk said. "As a researcher, this goal drives me to better understand health and disease, not only to improve oral health, but also overall health."

For Rajesh Lalla, B.D.S., Ph.D., professor of oral medicine and associate dean for research at the University of Connecticut School of Dental Medicine, his favorite part of being a researcher is the ability to create new knowledge.

"It is extremely satisfying to be able to go through the process of having an idea, designing a study to test that hypothesis and determining what the truth really is," said Dr. Lalla, who studies the oral side effects of radiation therapy and chemotherapy used in the treatment of cancer.

His research team is working to publish results from a multicenter clinical study that enrolled more than 500 patients undergoing radiation therapy for head and neck cancer.

"One of the novel findings is that the radiation treatment led to a striking increase in gingival recession," said Dr. Lalla, who is the immediate past president of the Multinational Association of Supportive Care in Cancer — the first dentist to hold the role. "It was known that these patients tend to get cervical caries after radiation therapy, but the reasons were not clear. Our finding indicates that exposure of the cervical areas of teeth due to gingival recession may explain the increased risk for cervical caries."

At the University of Connecticut, Dr. Lalla developed the dental school’s course on evidence-based decision making, which emphasizes the importance of evidence to the practice of dentistry.

"Dentistry is a scientific profession. The care we provide for our patients must be evidence based," said Dr. Lalla, who won the ADA’s 2020 Evidence-Based Dentistry Accomplished Faculty Award. "Research provides that evidence, so research is the very foundation of our profession."

With a background in engineering, Nathaniel Lawson, D.M.D., Ph.D., performs applied dental materials research at the University of Alabama at Birmingham School of Dentistry, where he is an associate professor, director of the biomaterials residency program and director of the division of biomaterials. He and his team devise testing equipment and protocols to evaluate dental materials to best predict their clinical performance, and they are perhaps most well known for performing wear testing. His lab is currently testing the wear of new 3D-printed materials being developed for dentures, crowns and occlusal guards.

"There are many different types of dental research. Many dentists may think of the incredible scientific work conducted by basic and translational scientists who are working to develop new treatments, materials and drugs to treat dental and oral conditions," said Dr. Lawson, who won the ADA's 2016 John W. Stanford New Investigator Award. "However, there is still research needed to evaluate the materials that are already in clinical use in order to determine the best uses of these materials. This information can help the clinician better perform work in their office."

Dr. Lawson began conducting research when he was applying to dental school at the University of Alabama. After a brief stint in clinical practice following graduation, his dental school research adviser asked if he would be interested in returning to his alma mater for an academic position performing research and teaching.

"Within a couple years of working in the position, I realized that I really loved what I was doing," Dr. Lawson said. "I really enjoy thinking of clinical problems, performing a study to try to better understand the best clinical treatment, trying what I learned in practice and then sharing that information through teaching."

Dr. Geisinger, too, was initially unsure of her career path and thought she would go into private practice until she began volunteering as a faculty member at a dental school.

"When I thought about the opportunity to make an exponential impact on our profession through education, research and service, I knew that I had to try to make the biggest impact I could on the oral health of patients and communities," she said. "And it is the research part of that mission that allows me to have the widest reach — impacting the global delivery of dental care through incremental discovery."

Dr. Geisinger, who is a member of the ADASRI Board of Directors and secretary-treasurer of the American Academy of Periodontology, is currently involved in a project examining best practices for delivering oral hygiene care to people with dementia in skilled nursing facilities, as well as the impact of periodontal health on the development and progression of dementia.

The research dentists perform has a lasting impact on not only the profession but public health as well.

"Dentists are an integral part of health care, and as an important health care provider, we need to base what we do on science and biology in order to offer evidence-based, scientifically proven and solid approaches to our patients," Dr. Hasturk said. "They are hungry to learn from us to do better at home and in their lives and to be examples to their children and young generations. We can only be better prepared for the future with proper education, and proper education is a result of research."

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How to Thrive as You Age

Rapamycin may slow aging. here's one way the drug will be tested.

Allison Aubrey

Anti-aging drug Rapamycin to prevent gum disease 

A generic drug that's used to treat transplant patients has been shown to extend the life span of some animals. Guido Mieth/Getty Images hide caption

A few years back, Matt Kaeberlein was diagnosed with a frozen shoulder. “It was really bad,” he recalls. He wasn’t sleeping well and couldn’t throw a ball due to the pain. His doctor recommended physical therapy, and told him that it may take a year to get better.

Feeling frustrated, he decided to try rapamycin. In recent years, some high-profile longevity scientists have started taking the drug in hopes of fending off age-related health problems. So far, it’s untested in people taking it for anti-aging, but rapamycin has been shown to extend the lifespan of mice .

“I decided to try it,” Kaeberlein says. It was his "first foray into biohacking,” and he was very pleased with what happened next. “Within two weeks, 50% of the pain was gone,” he says. And by the end of 10 weeks, he had regained range of motion and the pain was completely gone.

“And it hasn’t come back,” he says.

Kaeberlein is no stranger to rapamycin. He’s a biologist and co-founded the Dog Aging Project to study how rapamycin influences dogs’ healthspans. He’s also the former director of the Healthy Aging and Longevity Research Institute at the University of Washington.

Rapamycin was first approved by the FDA for use in transplant patients in the late 1990s. At high doses it suppresses the immune system. At low doses, Kaeberlein says it seems to help tamp down inflammation. It works by inhibiting a signaling pathway in the body called mTOR — which seems to be a key regulator of lifespan and aging.

Shots - Health News

Scientists can tell how fast you're aging. now, the trick is to slow it down.

The drug is not approved for pain or anti-aging, but some physicians prescribe rapamycin off-label with the aim of fending off age-related conditions. Kaeberlein and his colleagues surveyed about 300 of these patients, who take low doses, and many report benefits.

But anecdotes are no replacement for science. To figure out the risks and benefits of a drug, research is needed. And that's where a dentist comes in.

Dr. Jonathan An , at the University of Washington, has been granted FDA approval to test rapamycin in patients with gum disease — a common condition that tends to accelerate with age. When he treats patients with gum disease, he says there’s not much he can do beyond cleaning and removing the plaque — a buildup of bacteria. “All we’re doing is putting a bandage on,” he says. His goal is to find and treat the underlying cause of the disease.

There’s already some evidence from transplant patients that rapamycin may help improve oral health. And as part of the study, An and his collaborators will also measure changes in participants’ microbiomes and their biological clocks.

The study will enroll participants over the age of 50 who have gum disease. They will take the drug, at various doses, intermittently for 8 weeks. Then, An will be able to determine if the drug is safe and effective.

If rapamycin has a beneficial effect he says, it will help demonstrate that it’s possible to target the root cause of the disease. “It really comes down to targeting the biology of aging,” he says.

Dr. An thinks gum disease may be a kind of canary in the coalmine of age-related diseases. For instance, gum disease is linked to a higher risk of heart disease, and maybe dementia, too . Scientists say it’s possible that bacteria in the mouth linked to periodontal disease causes inflammation, which may cause a “cascade” of damage to blood vessels, leading to problems in the heart or brain.

“If we can target that underlying biology, we predict that it might address a lot of these other underlying conditions,” An says.

Rapamycin is a generic drug, so pharmaceutical companies have little incentive to fund new research. An and his collaborators have received a grant to conduct the trial, which could open the door to further studies to determine whether rapamycin can help prevent or slow down other age-related diseases.

Eric Verdin , a physician who heads the Buck Institute for Research on Aging, says his group is fundraising for more research on rapamycin. He says there are a lot of unanswered questions, for example “what is the effect of different concentrations in a single dose?” And he wants to look for a “molecular signature” in people taking rapamycin. He wants to know more about doses and intervals, since many doctors prescribing it off-label recommend cycling on and off the drug.

Researchers are also working on other drugs that may work in similar ways, and there’s a push for new drugs — or other interventions that target biological aging. There’s a new $100 million XPRIZE Healthspan competition , aimed at accelerating the research in the field supported by Hevolution and other funders.

For now, XPRIZE founder Peter Diamandis, a physician who writes about longevity, says he takes rapamycin. “I do six milligrams every Sunday night, so once a week," for three months, he explains. Then he takes a month off. "I believe that rapamycin — in the way I'm utilizing it — is safe and has more upside potential than downside,” he says.

Diamandis constantly monitors his body with many health metrics, and he acknowledges it’s hard to determine the effect of rapamycin given all the other things he does to stay healthy, including eating well, eliminating sugar, working out every day and prioritizing sleep.

His plan is to continue with healthy lifestyle habits while supporting research into interventions and strategies that can help people add more healthy years to their life.

A cheap drug may slow down aging. A study will determine if it works

Find Allison Aubrey on Instagram at  @allison.aubrey  and on X  @AubreyNPR .

This story was edited by Jane Greenhalgh

Could Stem Cells Eventually Repair Your Cavity With ‘Living Fillings?’

• Rowan Lynam

Featured Experts

• Stem Cells for 'Living Fillings'

Cavity Repair Now

The future of dentistry.

• 'Living Fillings' are Science Fiction for Now

Our teeth can’t repair themselves…but what if they could? The future of dentistry lies in the captivating field of regenerative medicine, where stem cell research is diving deep into the potential to repair damaged teeth with “living fillings.” But how far are we from ditching fillings for specialized tooth restoration? While the research is science fact, getting a “living filling” from your dentist is still science fiction…for now.

• Victoria Veytsman, DDS is a cosmetic dentist based in New York
• Salvator La Mastra, DDS is a cosmetic dentist based in Dallas, TX

Stem Cells for ‘Living Fillings’

“I find this field really fascinating,” says New York cosmetic dentist Victoria Veytsman, DDS. “The field of tissue engineering and regenerative medicine in dentistry is really at the forefront of where healthcare is going.”

Stem cells are those super useful specialized cells (found in adult body tissues and in embryos) that can be guided towards becoming many different cell types and can self-replicate. That makes them immensely useful in regenerative medicine, where the goal is to get the body’s repair processes engaged to handle damaged, diseased or otherwise unwell tissues. According to the California Institute for Regenerative Medicine , the most commonly used stem cell-based therapy is for bone marrow transplants.

“When it comes to filling a cavity with them, stem cells alone aren’t enough to complete the process of tooth restoration,” explains Dallas, TX cosmetic dentist Salvator La Mastra, DDS. “They would need a framework of some kind in order to form in the correct manner.”

Dr. Veytsman explains that current research is focused on creating that framework, creating a kind of “living filling.”

“We don’t want enamel to grow in a petri dish; we want it to grow on your tooth,” Dr. Veytsman says. “So the process requires a scaffold or matrix to support that growth.”

When a tooth develops a cavity, the first step is to remove the decay and stop the process of damage. “Cavities are caused by bacteria,” Dr. La Mastra explains. “That acid producing bacteria is what causes the cavitation of the tooth, which is the cavity itself and the decay. It’s basically necrotic tissue that we have to drill out.”

Then, you have to fill in what’s lost. “We do things like crowns and fillings to replace the chief structure that was lost or decayed,” Dr. Veytsman explains. “It’s called restorative dentistry because we’re trying to restore what’s been lost.”

Those fillings are made of amalgam (a mixture of metals) or composite resin filling materials (made from polymers and glass particles), and we know they’re safe, functional and that they won’t decay in the future. That’s something we can’t say about these “living fillings.”

“One thing about our current implants and fillings is that we know they won’t develop cavities down the line,” La Mastra says. “There are complications that could arise from the regenerative method that could cause more than just aesthetic consequences; your bite can also be impacted.”

“I think we’re just at the beginning of this technology,” Dr. Veytsman says. “But it definitely has the potential to change the way we approach cavities in the years to come.”

Stem cells could also be utilized outside of “living fillings” to benefit oral health. Aside from repairing enamel, stem cells could be used to encourage the growth of dentin, restore pulp, even regenerate lost gum tissues.

“You’re seeing the rise of stem cell banking now for these purposes,” Dr. Veytsman explains. “Harvesting and banking stem cells for future applications and to use as a preventative measure are growing in popularity.”

‘Living Fillings’ are Science Fiction for Now

“I think we’re multiple decades away from a changeover to regenerative medicine in dentistry,” La Mastra says. “I already have patients who ask me if they can just regrow their tooth, and we are nowhere near being able to do that.”

While “living fillings” aren’t going to enter your dentist’s office in the immediate future, there’s still reason to be excited.

“The advent of AI technologies is really accelerating this research,” Dr. Veytsman says. “And it’s letting us ask a ton of questions about possible applications. Can regenerative medicine deal with prevention? Can it help stop decay in the very early stages? We’re still so early in this process, but AI and regenerative medicine are really at the forefront of healthcare right now.”

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Integration of Primary and Oral Health Care—An Unrealized Opportunity

• 1 Division of General Internal Medicine and Primary Care, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
• 2 Harvard Medical School, Boston, Massachusetts
• 3 School of Dental Medicine, Stony Brook University, Stony Brook, New York

Primary care is the central component of a high-functioning and equitable health system. However, there is a shortage of primary care clinicians, and the time required to complete all recommended prevention services and counseling for a typical primary care panel is prohibitive. One solution is to use a team-based approach where a variety of professionals collaborate to meet patient needs. In 2021, the National Academies of Sciences, Engineering, and Medicine released a consensus report on implementing high-quality primary care, which emphasized the adoption of interprofessional teams and the use of nontraditional care settings to improve the quality and breadth of primary care in the US. 1 In this spirit, dentists are an important resource; they are medically trained and have longitudinal relationships with patients, who may not be seen by primary care clinicians.

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Simon L , Lamster I. Integration of Primary and Oral Health Care—An Unrealized Opportunity. JAMA Intern Med. Published online June 24, 2024. doi:10.1001/jamainternmed.2024.2267

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Caring for older Americans’ teeth and gums is essential, but Medicare generally doesn’t cover that cost

Frank Scannapieco , University at Buffalo and Ira Lamster , Stony Brook University (The State University of New York)

No, it’s not just sugary food that’s responsible for poor oral health in America’s children, especially in Appalachia

Daniel W. McNeil , West Virginia University and Mary L. Marazita , University of Pittsburgh

How did people clean their teeth in the olden days?

Jane Cotter , Texas A&M University

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INNOVATIONS IN PREVENTIVE DENTISTRY

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Preventive dentistry is a constantly changing and developing field: As new research emerges, some practices that had once been revolutionary are abandoned, while others continue to withstand the test of time. This book discusses new developments and innovations in preventive dentistry, from primary prevention to secondary prevention by inactivating initial lesions, and on to tertiary prevention to avoid subsequent progression and complications of manifest oral disease.

The book relies on a sound evidence base and instructs readers how this can be translated into clinical dental practice - what changes should be made to how we practice and why they should be made. Topics include caries and periodontal disease, orthodontic problems, diagnostic approaches, diet and oral health, oral hygiene, oral disease patterns, caries treatment, fluoride guidelines, risk management, sealants, and probiotics.

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WVU School of Pharmacy professor receives Governor’s highest honor

West Virginia Governor Jim Justice presented Dr. Elizabeth Scharman, professor emerita at the West Virginia University School of Pharmacy, with the 2024 Distinguished Mountaineer Award. This award is the highest honor the Governor can bestow upon a non-native West Virginian.

Dr. Scharman, who retired last month, served as the executive director of the West Virginia Poison Center for 32 years. During her tenure, she led operations such as the West Virginia DHHR Coronavirus Hotline, managed the Emergency Line, provided toxicology information during the 2014 Water Crisis, and worked across the state on poison prevention and toxicology education and treatment. Additionally, she played a key role as the deputy strategic national stockpile coordinator, contributing significantly to emergency preparedness planning within the state. 

Dr. Scharman holds certifications as a board-certified delegate of the American Board of Applied Toxicology and as a board-certified pharmacotherapy specialist. She previously chaired the Kanawha/Putnam Emergency Planning Committee and has been involved in various committees and editorial boards. Her scholarly contributions include numerous published articles and chapters in pharmacy textbooks. Among her many accolades are the WVU Health Sciences Women in Science and Health Advanced Career Excellence Awards in 2015, the American Academy of Clinical Toxicology's 2012 Distinguished Service Award, and the WVU School of Pharmacy's Outstanding Service Award in 2022.

Governor Justice's framed proclamation reads, “Scharman is a caring and giving person, and her dedication and commitment to her career and the great state of West Virginia have set an outstanding example for us all.”

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ANTI-SEMITIC ATTITUDES OF THE MASS PUBLIC: ESTIMATES AND EXPLANATIONS BASED ON A SURVEY OF THE MOSCOW OBLAST

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In this article we examine anti-Semitism as expressed by a sample of residents of the Moscow Oblast (Soviet Union). Based on a survey conducted in 1920, we begin by describing anti-Jewish prejudice and support for official discrimination against Jews. We discover a surprisingly low level of expressed anti-Semitism among these Soviet respondents and virtually no support for state policies that discriminate against Jews. At the same time, many of the conventional hypotheses predicting anti-Semitism are supported in the Soviet case. Anti-Semitism is concentrated among those with lower levels of education, those whose personal financial condition is deteriorating, and those who oppose further democratization of the Soviet Union. We do not take these findings as evidence that anti-Semitism is a trivial problem in the Soviet Union but, rather, suggest that efforts to combat anti-Jewish movements would likely receive considerable support from ordinary Soviet people.

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Sign in through society site

Many societies offer single sign-on between the society website and Oxford Academic. If you see ‘Sign in through society site’ in the sign in pane within a journal:

• Click Sign in through society site.
• When on the society site, please use the credentials provided by that society. Do not use an Oxford Academic personal account.

If you do not have a society account or have forgotten your username or password, please contact your society.

Sign in using a personal account

Some societies use Oxford Academic personal accounts to provide access to their members. See below.

A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.

Some societies use Oxford Academic personal accounts to provide access to their members.

Viewing your signed in accounts

Click the account icon in the top right to:

• View your signed in personal account and access account management features.
• View the institutional accounts that are providing access.

Signed in but can't access content

Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian.

For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more.

Short-term Access

To purchase short-term access, please sign in to your personal account above.

Don't already have a personal account? Register

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