Background. Opioids are still being prescribed to manage acute postsurgical pain. Unnecessary opioid prescriptions can lead to addiction and death, as unused tablets are easily diverted. Methods. To determine whether combination nonopioid analgesics are at least as good as opioid analgesics, a multisite, double-blind, randomized, stratified, noninferiority comparative effectiveness trial was conducted, which examined patient-centered outcomes after impacted mandibular third- molar extraction surgery. Participants were randomized to receive 5 mg of hydrocodone with 300 mg of acetaminophen (opioid) or 400 mg of ibuprofen and 500 mg of acetaminophen (nonopioid). After an initial dose, analgesic was taken every 4 through 6 hours as needed for pain. Results. In this randomized multisite clinical trial (n = 1,815 adults), those not taking opioids experienced significantly less pain (numeric rating scale ranging from 0 [no pain] through 10 [worst pain imaginable]) for first day and night (mean difference, -0.70; 95% CI, -0.94 to -0.45; P < .001) and second day and night (mean difference, -0.28; 95% CI, -0.52 to -0.04; P = .015), and experienced no more pain than participants taking opioids over the entire postoperative period (mean difference, -0.20; 98.75% CI, -0.45 to 0.05; P = .172). Participants not taking opioids had higher overall satisfaction at the postoperative visit (85.3% extremely satisfied or satisfied vs 78.9%; 95% CI, 1.21 to 1.98; P = .006). Conclusions. The ibuprofen and acetaminophen combination managed pain better for the first 2 days and led to greater satisfaction over the entire postoperative period than hydrocodone with acetaminophen. At no time did hydrocodone outperform the nonopioid.

Opioids are still being prescribed to manage acute postsurgical pain. Unnecessary opioid prescriptions can lead to addiction and death, as unused tablets are easily diverted.

The periodontal disease pathobiont Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) may exert a range of detrimental effects on periodontal diseases in general and, more specifically, with the initiation and progression of Localized Stage III Grade C periodontitis (molar–incisor pattern). In this review of the biogeography of this pathobiont, the full range of geographical scales for A. actinomycetemcomitans, from global origins and transmission to local geographical regions, to more locally exposed probands and families, to the individual host, down to the oral cavity, and finally, to spatial interactions with other commensals and pathobionts within the plaque biofilms at the micron/nanoscale, are reviewed. Using the newest technologies in genetics, imaging, in vitro cultures, and other research disciplines, investigators may be able to gain new insights to the role of this pathobiont in the unique initial destructive patterns of Localized Stage III Grade C periodontitis. These findings may incorporate the unique features of the microbiome that are influenced by variations in the geographic environment within the entire mouth. Additional insights into the geographic distribution of molar–incisor periodontal breakdown for Localized Stage III Grade C periodontitis may derive from the spatial interactions between A. actinomycetemcomitans and other pathobionts such as Porphyromonas gingivalis, Filifactor aclocis, and commensals such as Streptococcus gordonii. In addition, while the association of A. actinomycetemcomitans in systemic diseases is limited at the present time, future studies into possible periodontal disease–systemic disease links may also find A. actinomycetemcomitans and its geographical interactions with other microbiome members to provide important clues as to implications of pathobiological communications.

Periodontitis is a highly prevalent inflammatory illness that leads to the destruction of tooth supporting tissue structures and has been associated with an increased risk of cardiovascular disease (CVD). Precision medicine, an emerging branch of medical treatment, aims can further improve current traditional treatment by personalizing care based on one’s environment, genetic makeup, and lifestyle. Genomic databases have paved the way for precision medicine by elucidating the pathophysiology of complex, heritable diseases. Therefore, the investigation of novel periodontitis-linked genes associated with CVD will enhance our understanding of their linkage and related biochemical pathways for targeted therapies. In this article, we highlight possible mechanisms of actions connecting PD and CVD. Furthermore, we delve deeper into certain heritable inflammatory-associated pathways linking the two. The goal is to gather, compare, and assess high-quality scientific literature alongside genomic datasets that seek to establish a link between periodontitis and CVD. The scope is focused on the most up to date and authentic literature published within the last 10 years, indexed and available from PubMed Central, that analyzes periodontitis-associated genes linked to CVD. Based on the comparative analysis criteria, fifty-one genes associated with both periodontitis and CVD were identified and reported. The prevalence of genes associated with both CVD and periodontitis warrants investigation to assess the validity of a potential linkage between the pathophysiology of both diseases.

This review addresses the recent World Workshop Consensus Conference (WWCC) decision to eliminate Localized Aggressive Periodontitis (LAgP) in young adults as a distinct form of periodontitis. A “Consensus” implies widespread, if not unanimous, agreement among participants. However, a significant number of attendees were opposed to the elimination of the LAgP classification. The substantial evidence supporting a unique diagnosis for LAgP includes the (1) incisor/molar pattern of disease, (2) young age of onset, (3) rapid progression of attachment and bone loss, (4) familial aggregation across multiple generations, and (5) defined consortium of microbiological risk factors including Aggregatibacter actinomycetemcomitans. Distinctive clinical signs and symptoms of LAgP are presented, and the microbial subgingival consortia that precede the onset of signs and symptoms are described. Using Bradford–Hill guidelines to assess causation, well-defined longitudinal studies support the unique microbial consortia, including A. actinomycetemcomitans as causative for LAgP. To determine the effects of the WWCC elimination of LAgP on research, we searched three publication databases and discovered a clear decrease in the number of new publications addressing LAgP since the new WWCC classification. The negative effects of the WWCC guidelines on both diagnosis and treatment success are presented. For example, due to the localized nature of LAgP, the practice of averaging mean pocket depth reduction or attachment gain across all teeth masks major changes in disease recovery at high-risk tooth sites. Reinstating LAgP as a distinct disease entity is proposed, and an alternative or additional way of measuring treatment success is recommended based on an assessment of the extension of the time to relapse of subgingival re-infection. The consequences of the translocation of oral microbes to distant anatomical sites due to ignoring relapse frequency are also discussed. Additional questions and future directions are also presented.

PURPOSE:To investigate the stain preventing ability of a new chlorhexidine mouthwash while maintaining efficacy using a randomized clinical trial design. METHODS:98 subjects were enrolled and completed a 4-week clinical study that evaluated the effectiveness of the new mouthwash on plaque, gingivitis, and staining as compared to a commercially available chlorhexidine mouthwash. A subset of 62 subjects was evaluated for the effectiveness of the mouthwashes against plaque bacteria. RESULTS:After 4 weeks of use, the new chlorhexidine mouthwash reduced staining by 42.6% (P< 0.05) as compared to the commercially available mouthwash. The two mouthwashes were equivalent with regards to their effect on gingivitis, plaque, and plaque bacteria. CLINICAL SIGNIFICANCE:A new mouthwash, containing 0.12% chlorhexidine gluconate, has been developed that delivers stain reduction while maintaining equivalent efficacy to a commercially available chlorhexidine mouthwash with regards to gingivitis, plaque, and plaque bacteria. These findings should be considered by dental practitioners when making recommendations to patients whose teeth stain easily and need an anti-gingivitis and anti-plaque mouthwash.

Background During the COVID-19 pandemic, there was a substantial interruption of care, with patients and workers fearful to return to the dental office. As dental practice creates a highly aerosolized environment, the potential for spread of airborne illness is magnified. As a means to increase safety and mitigate risk, pre-visit testing for SARS-CoV-2 has the potential to minimize disease transmission in dental offices. The Pragmatic Return to Effective Dental Infection Control through Testing (PREDICT) Feasibility Study examined the logistics and impact of two different testing mechanisms (laboratory-based PCR viral testing and point-of-care antigen testing) in dental offices. Methods Dental healthcare workers (DHCWs) and patients in four dental offices within the National Dental Practice-based Research Network participated in this prospective study. In addition to electronic surveys, participants in two offices completed POC testing, while participants in two offices used lab-based PCR methods to detect SARS-CoV-2 infection. Analysis was limited to descriptive measures, with median and interquartile ranges reported for Likert scale responses and mean and standard deviation for continuous variables. Results Of the total 72 enrolled, 28 DHCWs and 41 patients completed the protocol. Two patients (4.9%) tested positive prior to their visit, while 2 DHCWs (12.5%) tested positive for SARS-CoV-2 infection at the start of the study. DHCWs and patients shared similar degree of concern (69% and 63%, respectively) for contracting COVID-19 from patients, while patients feared contracting COVID-19 from DHCWs less (49%). Descriptive statistics calculations revealed that saliva, tongue epithelial cells, and nasal swabs were the most desirable specimen collection method; both testing (LAB and POC) protocols took similar amounts of total time to complete; and DHCWs and patients reported feeling more comfortable when both groups were tested. Conclusions While a larger-scale, network study is necessary for generalizability of results, this feasibility study suggests that SARS-CoV-2 testing can be effectively implemented into dental practice workflows and positively impact perception of safety for DHCWs and patients. As new virulent infectious diseases emerge, preparing dental personnel to employ an entire toolbox of risk mitigation strategies, including testing, may have the potential to decrease dental practice closure time, maintaining continuity of dental care services for patients. Trial registration ClinicalTrials.gov: NCT05123742.

OBJECTIVES:Periodontal diseases are chronic, inflammatory disorders that involve the destruction of supporting tissues surrounding the teeth which leads to permanent damage and substantially heightens systemic exposure. If left untreated, dental, oral, and craniofacial diseases (DOCs), especially periodontitis, can increase an individual's risk in developing complex traits including cardiovascular diseases (CVDs). In this study, we are focused on systematically investigating causality between periodontitis with CVDs with the application of artificial intelligence (AI), machine learning (ML) algorithms, and state-of-the-art bioinformatics approaches using RNA-seq-driven gene expression data of CVD patients.MATERIALS AND METHODS:In this study, we built a cohort of CVD patients, collected their blood samples, and performed RNA-seq and gene expression analysis to generate transcriptomic profiles. We proposed a nexus of AI/ML approaches for the identification of significant biomarkers, and predictive analysis. We implemented recursive feature elimination, Pearson correlation, chi-square, and analysis of variance to detect significant biomarkers, and utilized random forest and support vector machines for predictive analysis.RESULTS:Our AI/ML analyses have led us to the preliminary conclusion that GAS5, GPX1, HLA-B, and SNHG6 are the potential gene markers that can be used to explain the causal relationship between periodontitis and CVDs.CONCLUSIONS:CVDs are relatively common in patients with periodontal disease, and an increased risk of CVD is associated with periodontal disease independent of gender. Genetic susceptibility contributing to periodontitis and CVDs have been suggested to some extent, based on the similar degree of heritability shared between both complex diseases.

Aggregatibacter actinomycetemcomitans ApiA is a trimeric autotransporter outer membrane protein (Omp) that participates in multiple functions, enabling A. actinomycetemcomitans to adapt to a variety of environments. The goal of this study is to identify regions in the apiA gene responsible for three of these functions: auto-aggregation, buccal epithelial cell binding, and complement resistance. Initially, apiA was expressed in Escherichia coli. Finally, wild-type A. actinomycetemcomitans and an apiA-deleted version were tested for their expression in the presence and absence of serum and genes related to stress adaptation, such as oxygen regulation, catalase activity, and Omp proteins. Sequential deletions in specific regions in the apiA gene as expressed in E. coli were examined for membrane proteins, which were confirmed by microscopy. The functional activity of epithelial cell binding, auto-aggregation, and complement resistance were then assessed, and regions in the apiA gene responsible for these functions were identified. A region spanning amino acids 186–217, when deleted, abrogated complement resistance and Factor H (FH) binding, while a region spanning amino acids 28–33 was related to epithelial cell binding. A 13-amino-acid peptide responsible for FH binding was shown to promote serum resistance. An apiA deletion in a clinical isolate (IDH781) was created and tested in the presence and/or absence of active and inactive serum and genes deemed responsible for prominent functional activity related to A. actinomycetemcomitans survival using qRT-PCR. These experiments suggested that apiA expression in IDH781 is involved in global regulatory mechanisms that are serum-dependent and show complement resistance. This is the first study to identify specific apiA regions in A. actinomycetemcomitans responsible for FH binding, complement resistance, and other stress-related functions. Moreover, the role of apiA in overall gene regulation was observed.

The purpose of this Editorial is to expose the gaps in the knowledge created by a decision by the World Workshop Consensus Conference (WWCC), held in 2017, which was focused on the re-classification of periodontal diseases [...]

Patients with diabetes mellitus (DM) have an increased risk of tooth decay caused by alterations in their tooth development and their oral environment, as well as a tendency to present with pulp infection due to compromised immune response. The present study analyzed the characteristic alterations in tooth development under DM conditions using incisors from db/db type 2 diabetic mouse model (T2DM mice). In micro-CT analyses, T2DM mice showed delayed dentin and enamel formation. Through transcriptomic analyses, pre-ameloblast- and pre-odontoblast-specific genes were found to be significantly decreased in the incisors of T2DM mice, whereas major ameloblast- and mature odontoblast-specific genes were not changed. Stem cell markers were decreased in T2DM mice compared to those from the control mice, suggesting that the stemness of dental pulp cells (DPCs) is attenuated in T2DM mice. In vitro analyses demonstrated that DPCs from T2DM mice have lower colony-forming units (CFU), slower propagation, and diminished differentiation characteristics compared to the control. These data suggest that T2DM conditions could impair the differentiation property of multiple progenitor/stem cells in the tooth, resulting in delayed tooth development in T2DM mice.

The oral cavity is thought to be one of the portals for SARS-CoV-2 entry, although there is limited evidence of active oral infection by SARS-CoV-2 viruses. We assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial cells (hTERT TIGKs), salivary gland epithelial cells (A-253), and oral buccal epithelial cells (TR146), which occupy different regions of the oral cavity, were challenged with replication-competent SARS-CoV-2 viruses and with pseudo-typed viruses expressing SARS-CoV-2 spike proteins. All oral epithelial cells expressing undetectable or low levels of human angiotensin-converting enzyme 2 (hACE2) but high levels of the alternative receptor CD147 were susceptible to SARS-CoV-2 infection. Distinct viral dynamics were seen in hTERT TIGKs compared to A-253 and TR146 cells. For example, levels of viral transcripts were sustained in hTERT TIGKs but were significantly decreased in A-253 and TR146 cells on day 3 after infection. Analysis of oral epithelial cells infected by replication-competent SARS-CoV-2 viruses expressing GFP showed that the GFP signal and SARS-CoV-2 mRNAs were not evenly distributed. Furthermore, we found cumulative SARS-CoV-2 RNAs from released viruses in the media from oral epithelial cells on day 1 and day 2 after infection, indicating productive viral infection. Taken together, our results demonstrated that oral epithelial cells were susceptible to SARS-CoV-2 viruses despite low or undetectable levels of hACE2, suggesting that alternative receptors contribute to SARS-CoV-2 infection and may be considered for the development of future vaccines and therapeutics.

Landscape ecology is a relatively new field of study within the sub-specialty of ecology that considers time and space in addition to structure and function. Landscape ecology contends that both the configuration (spatial pattern) and the composition (organisms both at the macro and or micro level) of an ecology can change over time. The oral cavity is an ideal place to study landscape ecology because of the variety of landscapes, the dynamic nature of plaque biofilm development, and the easy access to biofilm material. This review is intended to provide some specific clinical examples of how landscape ecology can influence the understanding of oral diseases and act as a supplement to diagnosis and treatment. The purpose of this review is two-fold; (1) to illustrate how landscape ecology can be used to clarify the two most prominent microbiologically induced infections in the oral cavity, and (2) how studies of oral microbiology can be used to enhance the understanding of landscape ecology. The review will distinguish between “habitat” and “niche” in a landscape and extend the concept that a “patch”, is the demarcating unit of a habitat within a landscape. The review will describe how; (1) an individual patch, defined by its shape, edges and internal components can have an influence on species within the patch, (2) spatial dynamics over time within a patch can lead to variations or diversities of species within that patch space, and (3) an unwelcoming environment can promote species extinction or departure/dispersion into a more favorable habitat. Understanding this dynamic in relationship to caries and periodontal disease is the focus of this review.

Professionals, including physicians, dentists, and lawyers, have earned a special place in society. They are characterized by a high level of education, devotion to selflessness and service, responsibility for self-governance, and adherence to a code of professional conduct.1 Dentists are governed by the American Dental Association's Principles of Ethics and Code of Professional Conduct, which incorporates 5 fundamental principles to form its foundation: Patient Autonomy ("self-governance"), Nonmaleficence ("do no harm"), Beneficence ("do good"), Justice ("fairness"), and Veracity ("truthfulness").

Introduction: Diabetes mellitus (DM) is a complex multisystemic disorder that affects an estimated 21 million Americans. No studies have evaluated the association of DM with the prevalence of each pulpal diagnosis. The objective of this study was to compare the prevalence of each pulp diagnosis including symptomatic irreversible pulpitis (SIP), asymptomatic irreversible pulpitis, reversible pulpitis, normal pulp, and pulp necrosis (PN) in DM patients against a nondiabetic control group. Methods: A retrospective chart review was approved by Rutgers University Institutional Review Board. The prevalence of the diagnoses SIP, asymptomatic irreversible pulpitis, reversible pulpitis, normal pulp, and PN was calculated from AxiUm (Exan software, Las Vegas, NV) electronic health records at Rutgers School of Dental Medicine. The chi-square test was used to see the relationship between the 2 categoric variables. Second, binary logistic regression analyses were performed for each group. Results: A total of 2979 teeth were diagnosed with a pulp condition between April 2013 and November 2018. The total tooth number of DM patients was 682, whereas the tooth number of nondiabetic patients was 2297. In the subgroup of patients younger than 40 years old, SIP was notably more prevalent in DM patients. In addition, the prevalence of PN in elderly DM patients (60-69 years old) was significantly higher than in the control group. Conclusions: The prevalence of SIP in DM patients was significantly higher compared with the control group (<40 years old), suggesting the possibility that DM could hypersensitize the subgroup of patients younger than 40 years old to pulpitis pain.

Background Dental practice has been greatly affected by the COVID-19 pandemic. As SARS-CoV-2 infection is transmitted by respiratory fluids, dental practice techniques, which include aerosol-generating procedures, can increase the risk of transmission causing heightened safety concerns for both dental health care workers (DHCWs) and patients. These concerns have resulted in the reduction in patient volume and the available workforce within dental practices across the United States. Standardized methods for COVID-19 triage and testing may lead to increased safety and perceptions of safety for DHCWs and their patients and promote willingness to provide and access oral health care services. Objective This study is designed to develop procedures that test the feasibility of enhanced COVID-19 triage and testing in dental offices. It will provide preliminary data to support a larger network-wide study grant application aimed at developing protocols to address safety concerns of patients and DHCWs in a peri–COVID-19 pandemic era. Methods The feasibility study is being conducted in 4 private dental practices, each of which has a dentist member of the National Dental Practice–Based Research Network. Participants include the DHCWs and patients of the dental practice. Study procedures include completion of COVID-19 triage, completion of COVID-19 testing (point-of-care [POC] or laboratory-based [LAB] SARS-CoV-2 viral, antigen, and antibody tests based on office designation), and administration of perception and attitude surveys for participating DCHWs and patients of the dental practice over a defined study period. The office designation and the participant’s role in the practice determines which testing protocol is executed within the office. There are 4 study groups following 4 distinct protocols: (1) POC DHCWs, (2) POC patients, (3) LAB DHCWs, and (4) LAB patients. Results Data collection began in December of 2021 and concluded in March 2022. Study results are expected to be published in fall 2022. Conclusions The results of this feasibility study will help identify the viability and functionality of COVID-19 triage and testing in dental practices and inform a larger network-wide study grant application that develops protocols that address safety concerns of patients and DHCWs in a COVID-19 environment. Trial Registration ClinicalTrials.gov NTC05123742; https://clinicaltrials.gov/ct2/show/NCT05123742?term=NCT05123742 International Registered Report Identifier (IRRID) DERR1-10.2196/38386

The COVID-19 pandemic underscores the need to address potential risk of transmission of infectious diseases among dental health care workers (DHCWs) and patients. As with the emergence of other novel pathogens, infection control protocols have changed dramatically1 over the past 2 years. Before the 1980s, dentists rarely wore eye protection, masks, or gloves. Our experience with HIV changed that. Today, our protocols include enhanced personal protective equipment, environmental disinfection, and ventilation upgrades.

Background : Everyday people die unnecessarily from opioid overdose-related addiction. Dentists are among the leading prescribers of opioid analgesics. Opioid seeking behaviors have been linked to receipt of initial opioid prescriptions following the common dental procedure of third molar extraction. With each opioid prescription a patient’s risk for opioid misuse or abuse increases. With an estimated 56 million tablets of 5 mg hydrocodone annually prescribed after third molar extractions in the United States, 3.5 million young adults may be unnecessarily exposed to opioids by dentists who are inadvertently increasing their patient’s risk for addiction. Methods : A double blind, stratified randomized, multi-center clinical trial has been designed to evaluate whether a combination of over-the-counter non-opioid containing analgesics is not inferior to the most prescribed opioid analgesic. The impacted 3rd molar extraction model is being used due to the predictable severity of the post-operative pain and generalizability of results. Within each site/clinic and gender type (male/female), patients are randomized to receive either OPIOID (hydrocodone/acetaminophen 5/300 mg) or NON-OPIOID (ibuprofen/acetaminophen 400/500 mg). Outcome data include pain levels, adverse events, overall patient satisfaction, ability to sleep, and ability to perform daily functions. To develop clinical guidelines and a clinical decision making tool, pain management, extraction difficulty and number of tablets taken is being collected enabling an experimental decision making tool to be developed. Discussion : The proposed methods address the short comings of other analgesic studies. Although prior studies have tested short-term effects of single doses of pain medications, patients and their dentists are interested in managing pain for the entire post-operative period, not just the first 12 hours. After surgery, patients expect to be able to perform normal daily functions without feeling nauseous or dizzy and they desire a restful sleep at night. Parents of young people are concerned with the risks of opioid use and misuse, either related to treatments received or to subsequent use of leftover pills. Upon successful completion of this clinical trial, dentists, patients, and their families will be better able to make informed decisions regarding post-operative pain management. Trial registration : ClinicalTrials.gov NCT04452344. Registered on June 20, 2020

Dental practice has been greatly affected by the COVID-19 pandemic. As SARS-COV-2 infection is transmitted by respiratory fluids, dental practice techniques, which include aerosol-generating procedures, can increase the risk of transmission causing heightened safety concerns for both dental health care workers (DHCWs) and patients. These concerns have resulted in the reduction in patient volume and the available workforce within dental practices across the United States. Standardized methods for COVID-19 triage and testing may lead to increased safety and perceptions of safety for DHCWs and their patients and promote willingness to provide and access oral healthcare services. This study is designed to develop procedures that test the feasibility of enhanced COVID-19 triage and testing in dental offices. It will provide preliminary data to support a larger network-wide study grant application aimed at developing protocols to address safety concerns of patients and DHCWs in a peri-COVID-19 pandemic era. The feasibility study is being conducted in four private dental practices, each of which has a dentist member of the National Dental Practice-Based Research Network. Participants include the DHCWs and patients of the dental practice. Study procedures include completion of COVID-19 triage, completion of COVID-19 testing [Point-of-Care (POC) or laboratory based (LAB) Laboratory (LAB) SARS-CoV-2 viral, antigen and/or antibody tests based on office designation] and administration of perception and attitude surveys for participating DCHWs and patients of the dental practice over a defined study period. The office designation and participant’s role in the practice determines which testing protocol is executed within the office. There are four study groups following four distinct protocols: (1) POC DHCWs, (2) POC Patients, (3) LAB DHCWs, and (4) LAB Patients. This work has been peer reviewed and funded by the National Institute of Dental and Craniofacial Research (NIDCR), an institute within the National Institute of Health (NIH). Study protocols commenced in December of 2021 and are expected to end in March 2022 with data analysis to follow. The results of this feasibility study will help identify viability and functionality of COVID-19 triage and testing in dental practices and inform a larger network-wide study grant application that develops protocols that address safety concerns of patients and Dental Health Care Workers (DHCWs) in a COVID-19 environment. The ClinicalTrials.gov registration is NTC05123742.

The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics. This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest (CNC)-like cells (CNCLCs); these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells (iPSCs). CNC is the anterior region of the neural crest in vertebrate embryos, which contains the primordium of dental pulp cells or odontoblasts. The produced CNCLCs showed approximately 2.5-12,000-fold upregulations of major CNC marker genes. Furthermore, the CNCLCs exhibited remarkable odontoblastic differentiation ability, especially when treated with a combination of the fibroblast growth factors (FGFs) FGF4 and FGF9. The FGFs induced odontoblast marker genes by 1.7-5.0-fold, as compared to bone morphogenetic protein 4 (BMP4) treatment. In a mouse subcutaneous implant model, the CNCLCs briefly fated with FGF4 + FGF9 replicated dental pulp tissue characteristics, such as harboring odontoblast-like cells, a dentin-like layer, and vast neovascularization, induced by the angiogenic self-assembling peptide hydrogel (SAPH), SLan. SLan acts as a versatile biocompatible scaffold in the canal space. This study demonstrated a successful collaboration between regenerative medicine and SAPH technology.