Variations in the alveolar bone morphology in maxillary molar area: a retrospective CBCT study.

BACKGROUND: This study quantitatively analyzed the anatomic structure of the alveolar bone in the maxillary molar region at three potential locations for Temporary Anchorage Device (TAD) placement. Additionally, the study compared the variability in this region across different age groups, sagittal skeletal patterns, vertical facial types, and sexes. METHODS: In this retrospective cone-beam computed tomography study, the buccal alveolar bone was analyzed in the posterior molar area of 200 patients, the measurement items include buccal alveolar bone height, alveolar bone thickness, interradicular distance, and maxillary retromolar space. RESULTS: Buccal alveolar height was greatest in the U56 region. The interradicular space was largest in the U56 region and increased from the alveolar crest to the sinus floor. Buccal alveolar bone thickness was highest in the U67 region and generally increased from the alveolar crest to the sinus floor. The maxillary retromolar space gradually increased from the alveolar crest to the root apex. CONCLUSIONS: TADs are safest when placed in the buccal area between the maxillary second premolar and the first molar, particularly at the 9 mm plane. The U67 region is the optimal safe zone for TAD placement for maxillary dentition distalization. TADs placement in adolescents can be challenging. Maxillary third molar extraction can be considered for maxillary dentition distalization.

The performance of electrode ultrafiltration membrane bioreactor in treating cosmetics wastewater and its anti-fouling properties.

The membrane fouling problem of the membrane bioreactor (MBR) for wastewater treatment reduces the membrane flux and the pollutants removal efficiencies, which is the major obstacle limiting its application and should be properly solved. The combination of membrane and electricity can effectively slow down the membrane fouling rate due to electric repulsion between the pollutants and the membrane. In this study, the performance and the membrane fouling features of an electrode ultrafiltration membrane bioreactor (EMBR) fed with cosmetics wastewater were compared with a conventional ultrafiltration membrane bioreactor (UMBR). The results showed the COD removal efficiency increased by 4.43% and the transmembrane pressure (TMP) reduced by 50% in the EMBR as compared with the UMBR. The specific surface areas of electrode ultrafiltration membrane and conventional ultrafiltration membrane declined by 56.9% and 78.8% after 90 days of operation, respectively. The Protein (PN), polysaccharide (PS) and humic acids (HA) in the cake layer of EMBR were only 61.27%, 78.37% and 34.85% of that of UMBR, which contributed to its loose and porous structure and thus decreased the growth rate of TMP and extended the operation cycle. Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory calculation proved that the energy barrier between the electrode ultrafiltration membrane and the pollutants was 50% higher than that between the conventional ultrafiltration membrane and the pollutants. Therefore, the strong anti-fouling property of the electrode ultrafiltration membrane could reduce the chemicals dosage and manpower consumption for membrane cleaning and could be preferred for the treatment of cosmetics or alike wastewater containing high concentrations of surfactants and fatty acids.

Dental pulp stem cell-derived exosomes suppress M1 macrophage polarization through the ROS-MAPK-NFκB P65 signaling pathway after spinal cord injury.

Stem cell-derived exosomes have recently been regarded as potential drugs for treating spinal cord injury (SCI) by reducing reactive oxygen species (ROS) and suppressing M1 macrophage polarization. However, the roles of ROS and exosomes in the process of M1 macrophage polarization are not known. Herein, we demonstrated that ROS can induce M1 macrophage polarization and have a concentration-dependent effect. ROS can induce M1 macrophage polarization through the MAPK-NFκB P65 signaling pathway. Dental pulp stem cell (DPSC)-derived exosomes can reduce macrophage M1 polarization through the ROS-MAPK-NFκB P65 signaling pathway in treating SCI. This study suggested that DPSC-derived exosomes might be a potential drug for treating SCI. Disruption of the cycle between ROS and M1 macrophage polarization might also be a potential effective treatment by reducing secondary damage.

Novel Therapeutic Platform of Micelles and Nanogels from Dopa-Functionalized Triblock Copolymers.

Multi-drug delivery systems constructed from a basic polymeric scaffold, and which have the ability to target a variety of biomedical applications, can streamline the development of nanomedicine to provide both environmental and economical relief. Herein, amphiphilic ABA-triblock copolymers are synthesized and assembled sequentially into micelles and nanogels as drug delivery systems following a thorough evaluation on advanced in vitro models to explore their potential for the treatment of cancer and bacterial infections. Short blocks of 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) are oligomerized from PEG6k and thereafter functionalized with dihydroxyphenylalanine (dopa)-functional thiols using thiol-ene coupling (TEC) click chemistry. The copolymers self-assemble into well-defined micelles in aqueous solution and are further formulated into nanogels via UV-induced TEC. The resulting spherical micelles and nanogels are stable nanoparticles, with sizes ranging between 100 and 200 nm. The nanogels are found to be non-toxic to a panel of cell lines and mask the toxicity of the potent drugs until their release. The nanogels would be superior to micelles for the elimination of cancer cells supported by both 2D cell culture and a 3D spheroid model. The opposite conclusion could be drawn for bacteria inhibition.

UV-Cured Antibacterial Hydrogels Based on PEG and Monodisperse Heterofunctional Bis-MPA Dendrimers.

Bacterial infections are one of the major threats to human health due to the raising crisis of antibiotic resistance. Herein, second generation antibacterial heterofunctional dendrimers based on 2,2-bis(methylol)propionic acid were synthesized. The dendrimers possessed six alkenes and 12 ammonium end-groups per molecule and were used to fabricate antibacterial hydrogels together with dithiol-functional polyethylene glycol (mol wt of 2, 6 and 10 kDa) as crosslinkers via thiol-ene chemistry. The network formation can be completed within 10 s upon UV-irradiation as determined by the stabilization of the storage modulus in a rheometer. The hydrogels swelled in aqueous media and could be functionalized with the N-hydroxysuccinimide ester of the dye disperse red 13, which allowed for visually studying the degradation of the hydrogels through the hydrolysis of the ester bonds of the dendritic component. The maximum swelling ratio of the gels was recorded within 4-8 h and the swelling ratios increased with higher molecular weight of the polyethylene glycol crosslinker. The gel formed with 10 kDa polyethylene glycol crosslinker showed the highest swelling ratio of 40 and good mechanical properties, with a storage modulus of 8 kPa. In addition, the hydrogels exhibited good biocompatibility towards both human fibroblasts and mouse monocytes, while showing strong antibacterial activity against both gram-positive and gram-negative bacteria.

AFF4 enhances odontogenic differentiation of human dental pulp cells.

AFF4 is a component of super elongation complex (SECs) and functions as a scaffold protein to bridge the transcription elongation factors. It is associated with leukemia, HIV transcription, and head neck cancer. However, its role in odontogenic differentiation of dental pulp cells (DPCs) is unclear. Here, we show the expression of AFF4 is increased during odontogenesis. Depletion of AFF4 in human DPCs leads to a decrease of alkaline phosphatase (ALP) activity, calcium mineralization and odontogenic-related genes expression. On the contrary, Lentivirus-mediated overexpression of AFF4 induces the odontogenic potential of DPCs. Mechanistically, we found AFF4 regulates the transcription of NFIC, a key factor for tooth root formation. Overexpression of NFIC successfully rescues the restricted differentiation of AFF4-depleted cells. Our data demonstrate that AFF4 serves as a previously unknown regulator of odontogenesis.

Synthesis of Heterofunctional Polyester Dendrimers with Internal and External Functionalities as Versatile Multipurpose Platforms.

Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weight, number, and location of different cargos across the whole dendritic skeleton. Consequently, these dendrimers with multipurpose characters are the pinnacle of precision polymers and thereof are highly attractive to the scientific community as they can find use in a great number of cutting-edge applications, especially as discrete unimolecular carriers for therapeutic exploitation. Unfortunately, most established dendrimer families display external functionalities but lack internal scaffolding ability, which leads to inherent limitations to their full potential use as precision carriers. Consequently, here, we embark on a novel synthetic strategy facilitating the introduction of internal functionalization of established dendrimers. As a proof of concept, a new class of internally and externally functionalized multipurpose dendrimers based on the established 2,2-bis(methylol)propionic acid (bis-MPA) was successfully obtained by the elegant and simple design of AB2C monomers, amalgamated from two traditional AB2 monomers. Utilizing fluoride-promoted esterification (FPE), straightforward layer-by-layer divergent growth up to the fourth generation was successful in less than one day of reaction time, with a molecular weight of 15 kDa, and displaying 93 reactive groups divided by 45 internal and 48 external functionalities. The feasibility of postfunctionalization through click reactions is demonstrated, where the fast and effective attachment of drugs, dyes, and PEG chains is achieved, as well as cross-linking into multifunctional hydrogels. The simplicity and versatility of the presented strategy can easily be transferred to generate a myriad of functional materials such as polymers, surfaces, nanoparticles, or biomolecules.

Degradable High Molecular Weight Monodisperse Dendritic Poly(ethylene glycols).

Poly(ethylene glycols) (PEGs) are extensively explored by the pharma industry as foundations for new therapeutic products. PEGs are typically used for their conjugation to active drugs, peptides, and proteins and the likeliness to increase the half-life and enhance the therapeutic outcome. Considering the necessity of batch-to-batch consistency for clinical products, monodisperse PEGs are highly attractive but are generally limited to 5 kDa as an upper molecular weight (Mw) and with an oligomer purity of 95%. By amalgamating short, monodisperse PEGs with dendritic frameworks based on 2,2-bis(methylol)propionic acid polyesters, we showcase a robust synthetic approach to monodisperse PEGs with Mw ranging from 2 to 65 kDa. The latter is, to our knowledge, the highest Mw structure of its kind ever reported. Importantly, the dendritic multifunctional connector facilitated degradability at pH 7.4 at 37 °C, which is an important feature for the delivery of therapeutic agents.

Evaluation of Amino-Functional Polyester Dendrimers Based on Bis-MPA as Nonviral Vectors for siRNA Delivery.

Herein, we present the first evaluation of cationic dendrimers based on 2,2-bis(methylol)propionic acid (bis-MPA) as nonviral vectors for transfection of short interfering RNA (siRNA) in cell cultures. The study encompassed dendrimers of generation one to four (G1⁻G4), modified to bear 6⁻48 amino end-groups, where the G2⁻G4 proved to be capable of siRNA complexation and protection against RNase-mediated degradation. The dendrimers were nontoxic to astrocytes, glioma (C6), and glioblastoma (U87), while G3 and G4 exhibited concentration dependent toxicity towards primary neurons. The G2 showed no toxicity to primary neurons at any of the tested concentrations. Fluorescence microscopy experiments suggested that the dendrimers are highly efficient at endo-lysosomal escape since fluorescently labeled dendrimers were localized specifically in mitochondria, and diffuse cytosolic distribution of fluorescent siRNA complexed by dendrimers was observed. This is a desired feature for intracellular drug delivery, since the endocytic pathway otherwise transfers the drugs into lysosomes where they can be degraded without reaching their intended target. siRNA-transfection was successful in C6 and U87 cell lines using the G3 and G4 dendrimers followed by a decrease of approximately 20% of target protein p42-MAPK expression.

Synthesis and in Vitro Evaluation of Monodisperse Amino-Functional Polyester Dendrimers with Rapid Degradability and Antibacterial Properties.

Amine functional polymers, especially cationically charged, are interesting biomacromolecules for several reasons, including easy cell membrane entrance, their ability to escape endosomes through the proton sponge effect, spontaneous complexation and delivery of drugs and siRNA, and simple functionalization in aqueous solutions. Dendrimers, a subclass of precision polymers, are monodisperse and exhibit a large and exact number of peripheral end groups in relation to their size and have shown promise in drug delivery, biomedical imaging and as antiviral agents. In this work, hydroxyl functional dendrimers of generation 1 to 5 based on 2,2-bis(methylol)propionic acid (bis-MPA) were modified to bear 6 to 96 peripheral amino groups through esterification reactions with beta-alanine. All dendrimers were isolated in high yields and with remarkable monodispersity. This was successfully accomplished utilizing the present advantages of fluoride-promoted esterification (FPE) with imidazole-activated monomers. Straightforward postfunctionalization was conducted on a second generation amino-functional dendrimer with tetraethylene glycol through NHS-amidation and carbonyl diimidazole (CDI) activation to full conversion with short reaction times. Fast biodegradation of the dendrimers through loss of peripheral beta-alanine groups was observed and generational- and dose-dependent cytotoxicity was evaluated with a set of cell lines. An increase in neurotoxicity compared to hydroxyl-functional dendrimers was shown in neuronal cells, however, the dendrimers were slightly less neurotoxic than commercially available poly(amidoamine) dendrimers (PAMAMs). Additionally, their effect on bacteria was evaluated and the second generation dendrimer was found unique inhibiting the growth of Escherichia coli at physiological conditions while being nontoxic toward human cells. Finally, these results cement a robust and sustainable synthetic route to amino-functional polyester dendrimers with interesting chemical and biological properties.

Age-related alveolar bone maladaptation in adult orthodontics: finding new ways out.

Compared with teenage patients, adult patients generally show a slower rate of tooth movement and more pronounced alveolar bone loss during orthodontic treatment, indicating the maladaptation of alveolar bone homeostasis under orthodontic force. However, this phenomenon is not well-elucidated to date, leading to increased treatment difficulties and unsatisfactory treatment outcomes in adult orthodontics. Aiming to provide a comprehensive knowledge and further inspire insightful understanding towards this issue, this review summarizes the current evidence and underlying mechanisms. The age-related abatements in mechanosensing and mechanotransduction in adult cells and periodontal tissue may contribute to retarded and unbalanced bone metabolism, thus hindering alveolar bone reconstruction during orthodontic treatment. To this end, periodontal surgery, physical and chemical cues are being developed to reactivate or rejuvenate the aging periodontium and restore the dynamic equilibrium of orthodontic-mediated alveolar bone metabolism. We anticipate that this review will present a general overview of the role that aging plays in orthodontic alveolar bone metabolism and shed new light on the prospective ways out of the impasse.

Significantly improved antifouling capability of silicone rubber surfaces by covalently bonded acrylated agarose towards biomedical applications.

Bacteria have the extraordinary ability to adhere to biomaterial surfaces and form multicellular structures known as biofilms, which have a detrimental impact on the performance of medical devices. Herein, an investigation highlighted the effective inhibition of bacteria adhesion and overgrowth on silicone rubber surface by grafting polysaccharide, agarose (AG), to construct hydrophilic and negatively charged surfaces. Because of the strong hydration capacity of agarose, the water contact angle of the modified silicone rubber surfaces was significantly reduced from 107.6 ± 2.7° to 19.3 ± 2.6°, which successfully limited bacterial adherence. Most importantly, the durability and stability of coating were observed after 10 days of simulated dynamic microenvironment in vivo, exhibiting a long service life. This modification method did not compromise biocompatibility of silicone rubber, opening a door to new applications for silicone rubber in the field of biomedical materials.

Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections.

Antimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK-060, a human kininogen-derived AMP. Once embedded into the poloxamer gel, DPK-060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time-kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti-infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK-060 at the wound site, all formulations display superior efficacy compared to DPK-060 in solution.

The Deubiquitinase OTUD1 Suppresses Secretory Neutrophil Polarization And Ameliorates Immunopathology of Periodontitis.

Tissue-infiltrating neutrophils (TINs) secrete various signaling molecules to establish paracrine communication within the inflammatory milieu. It is imperative to identify molecular mediators that control this secretory phenotype of TINs. The present study uncovers a secretory neutrophil subset that exhibits increased pro-inflammatory cytokine production and enhanced migratory capacity which is highly related with periodontal pathogenesis. Further analysis identifies the OTU domain-containing protein 1 (OTUD1) plays a regulatory role in this secretory neutrophil polarization. In human and mouse periodontitis, the waning of inflammation is correlated with OTUD1 upregulation, whereas severe periodontitis is induced when neutrophil-intrinsic OTUD1 is depleted. Mechanistically, OTUD1 interacts with SEC23B, a component of the coat protein II complex (COPII). By removing the K63-linked polyubiquitin chains on SEC23B Lysine 81, the deubiquitinase OTUD1 negatively regulates the COPII secretory machinery and limits protein ER-to-Golgi trafficking, thus restricting the surface expression of integrin-regulated proteins, CD9 and CD47. Accordingly, blockade of protein transport by Brefeldin A (BFA) curbs recruitment of Otud1-deficient TINs and attenuates inflammation-induced alveolar bone destruction. The results thus identify OTUD1 signaling as a negative feedback loop that limits the polarization of neutrophils with secretory phenotype and highlight the potential application of BFA in the treatment of periodontal inflammation.

Endocytic uptake and intracellular trafficking of bis-MPA-based hyperbranched copolymer micelles in breast cancer cells.

Dendrimers and their less well-defined cousins, hyperbranched polymers, are widely investigated as scaffold materials in tissue engineering, as drug delivery agents, and in diagnostic imaging applications. Despite the large interest of using these unique materials as polymer-based nanoparticles in biomedical applications, a clear understanding of the cellular uptake and transport of these polyester-based nanoparticles is still lacking. The objective of this study is to evaluate the cellular uptake profiles and intracellular trafficking of polymer micelles built from the hyperbranched polyester Boltorn, fitted with poly(ethylene glycol) and fluorescent groups in MDA-MB468 breast cancer cells. Results show that the uptake of these nanoparticles correlated positively to both time and concentration, and that the uptake of the nanoparticles was energy dependent. These polyesterbased nanoparticles appear to translocate across cells via clathrin- and macropinocytosis-mediated endocytosis. Observations of the intracellular trafficking of the nanoparticles indicate that particles could be released from early endosomes after being internalized, and the particles exhibit perinuclear localization. The uptake behavior of the nanoparticles was further evaluated in a range of cell lines. These results allow the generation of the knowledge base required to design polyester-based nanocarriers that can be used efficiently and specifically for drug delivery applications and imaging applications.

Confinement anisotropy drives polar organization of two DNA molecules interacting in a nanoscale cavity.

There is growing appreciation for the role phase transition based phenomena play in biological systems. In particular, self-avoiding polymer chains are predicted to undergo a unique confinement dependent demixing transition as the anisotropy of the confined space is increased. This phenomenon may be relevant for understanding how interactions between multiple dsDNA molecules can induce self-organized structure in prokaryotes. While recent in vivo experiments and Monte Carlo simulations have delivered essential insights into this phenomenon and its relation to bacteria, there are fundamental questions remaining concerning how segregated polymer states arise, the role of confinement anisotropy and the nature of the dynamics in the segregated states. To address these questions, we introduce an artificial nanofluidic model to quantify the interactions of multiple dsDNA molecules in cavities with controlled anisotropy. We find that two dsDNA molecules of equal size confined in an elliptical cavity will spontaneously demix and orient along the cavity poles as cavity eccentricity is increased; the two chains will then swap pole positions with a frequency that decreases with increasing cavity eccentricity. In addition, we explore a system consisting of a large dsDNA molecule and a plasmid molecule. We find that the plasmid is excluded from the larger molecule and will exhibit a preference for the ellipse poles, giving rise to a non-uniform spatial distribution in the cavity that may help explain the non-uniform plasmid distribution observed during in vivo imaging of high-copy number plasmids in bacteria.

A rapid staged protocol for efficient recovery of microplastics from soil and sediment matrices based on hydrophobic separation.

Microplastics (MPs) in soil and sediment (SS) matrices are emerging pollution hazards to ecosystems and humans. To mitigate MP pollution, suitable extractors and associated extracting solutions are required to efficiently separate MPs from SS matrices. In this study, we introduced a four-stage microplastic extractor (ME) device and investigated the fractional separation efficiencies of three extracting solutions (ultrapure water, saturated NaCl, and corn oil-in-NaCl) plus aeration, magnetic stirring, and electric stirring for three kinds of SS matrices (loam soil, sandy sediment, and muddy sediment) with four types of virgin MP pellets (acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polypropylene, and polystyrene). In addition, fragments of these four types of post-consumer MPs were also tested by the ME device. The mean recovery efficiencies of these MPs in the three SS matrices were 88.3 %-100 %. Oil-in-NaCl further improved the recovery efficiencies for the denser ABS and PC up to 40 % based on NaCl extraction.

DPSCs Protect Architectural Integrity and Alleviate Intervertebral Disc Degeneration by Regulating Nucleus Pulposus Immune Status.

Intervertebral disc (IVD) degeneration is the primary cause for low back pain that has a high prevalence in modern society and poses enormous economic burden on patients. Few effective therapeutic strategies are available for IVD degeneration treatment. To understand the biological effects of dental pulp stem cells (DPSCs) on nucleus pulposus (NP) cells, we carried out RNA sequencing, bioinformatic analysis which unveiled gene expression differences, and pathway variation in primarily isolated patients' NP cells after treatment with DPSCs supernatant. Western blot and immunofluorescence were used to verify these molecular alterations. Besides, to evaluate the therapeutic effect of DPSCs in IVD degeneration treatment, DPSCs were injected into a degeneration rat model in situ, with treatment outcome measured by micro-CT and histological analysis. RNA sequencing and in vitro experiments demonstrated that DPSCs supernatant could downregulate NP cells' inflammation-related NF-κB and JAK-STAT pathways, reduce IL-6 production, increase collagen II expression, and mitigate apoptosis. In vivo results showed that DPSCs treatment protected the integrity of the disc structure, alleviated extracellular matrix degradation, and increased collagen fiber expression. In this study, we verified the therapeutic effect of DPSCs in an IVD degeneration rat model and elucidated the underlying molecular mechanism of DPSCs treatment, which provides a foundation for the application of DPSCs in IVD degeneration treatment.

Heparinized anticoagulant coatings based on polyphenol-amine inspired chemistry for blood-contacting catheters.

Blood-contacting catheters occupy a vital position in modern clinical treatment including but not limited to cardiovascular diseases, but catheter-related thrombosis associated with high morbidity and mortality remains a major health concern. Hence, there is an urgent need for functionalized catheter surfaces with superior hemocompatibility that prevent protein adsorption and thrombus formation. In this work, we developed a strategy for constructing a kind of polyphenol-amine coating on the TPU surface (TLA) with tannic acid and lysine via simple dip-coating, inspired by dopamine adhesion. Based on the long-term stability and modifiable properties of TLA coatings, heparin was introduced by an amide reaction to provide anticoagulant activity (TLH). X-ray photoelectron spectroscopy and surface zeta potential measurements fully indicated the successful immobilization of heparin. Water contact angle measurements demonstrated good hydrophilicity and stability for 15 days of TLH coatings. Furthermore, the TLH coatings exhibited significant hemocompatibility and no cytotoxicity. The good antithrombotic properties of the functionalized surfaces were confirmed by an ex vivo blood circulation model. The present work is supposed to find potential clinical applications for preventing surface-induced thrombosis of blood-contacting catheters.

Challenges of Stem-cell-based Craniofacial Regeneration.

Oral diseases, such as dental caries, pulpitis, periodontitis, and craniofacial trauma, are common. Some individuals suffer from oral cancer or congenital craniofacial defects. The oral-systemic disease link reveals that a dental disorder is not a minor problem. Tissue loss is an inevitable consequence of most oral diseases, and repairing the tissue loss and restoring craniofacial function are highly expected by patients and are terminal targets of dental treatment. The current clinical approach for tissue loss due to dental caries, pulpitis, periodontitis, oral cancer, trauma, and developmental diseases depends on the filling of corresponding material, allograft, or autograft bone after lesion removal. Repair of the tissue volume is expectedly followed by promising functional restoration using regenerative dental tissue or tissue engineering, which has currently aroused the interest of clinicians and researchers. This review focuses on the ideas and recent findings on newly identified skeletal stem cells (SSCs) as candidates for craniofacial regeneration, signaling regulation of SSCs extended from embryonic development, and signal molecule delivery for the repair of the craniofacial defect, sincerely hoping that the hypothesis of craniofacial self-healing is true in the future.