Spatiotemporally controlled microchannels of periodontal mimic scaffolds. Park C H,Kim K H,Rios H F,Lee Y M,Giannobile W V,Seol Y J Journal of dental research Physiologic bioengineering of the oral, dental, and craniofacial complex requires optimized geometric organizations of fibrous connective tissues. A computer-designed, fiber-guiding scaffold has been developed to promote tooth-supporting periodontal tissue regeneration and functional restoration despite limited printing resolution for the manufacture of submicron-scaled features. Here, we demonstrate the use of directional freeze-casting techniques to control pore directional angulations and create mimicked topographies to alveolar crest, horizontal, oblique, and apical fibers of natural periodontal ligaments. For the differing anatomic positions, the gelatin displayed varying patterns of ice growth, determined via internal pore architectures. Regardless of the freezing coordinates, the longitudinal pore arrangements resulted in submicron-scaled diameters (~50 µm), along with corresponding high biomaterial porosity (~90%). Furthermore, the horizontal + coronal ([Formula: see text]) freezing orientation facilitated the creation of similar structures to major fibers in the periodontal ligament interface. This periodontal tissue-mimicking microenvironment is a potential tissue platform for the generation of naturally oriented ligamentous tissues consistent with periodontal ligament neogenesis. 10.1177/0022034514550716
    Accuracy of digital complete dentures: A systematic review of in vitro studies. Wang Can,Shi Yi-Fei,Xie Pei-Jin,Wu Jun-Hua The Journal of prosthetic dentistry STATEMENT OF PROBLEM:Reports on digital complete dentures (CDs) are increasing. However, systematic reviews on their accuracy and influencing factors are lacking. PURPOSE:The purpose of this systematic review was to evaluate the accuracy of digital CDs and to summarize influencing factors. MATERIAL AND METHODS:An electronic search of the English language literature from January 2009 to October 2019 was performed in the database PubMed/MEDLINE, with the results enriched by manual searches and citation mining. Factors investigated in the selected articles included the fabrication technique, type of computer-aided design and computer-aided manufacturing (CAD-CAM) system, shape of reference model, long-term service, analytical method, and statistical indicators. RESULTS:A total of 522 articles were identified, of which 14 in vitro articles met the inclusion criteria. Eight articles compared the adaptation of the denture base between digital and conventional methods, 4 studies evaluated the occlusal discrepancies, 4 compared the trueness or adaptation of the denture fabricated with CAD-CAM milling and 3D printing, 1 compared the denture adaptation with 4 different CAD-CAM systems, and 2 evaluated the adaptation of the denture base before and after incubation in artificial saliva. CONCLUSIONS:Most of the studies reported clinically acceptable values for the occlusal trueness and adaptation of digital CDs. The digital CDs showed similar or better adaptation than conventionally fabricated CDs, and the greatest misfit of the intaglio surface was reported in the posterior palatal seal area and border seal area. The fabrication technique, CAD-CAM system, and long-term service were statistically significant in relation to denture accuracy. Clarification is needed concerning the accuracy of digital CDs according to the shape of the cast, the parameters related to the CAD-CAM process, the analytical method, and the statistical indicators. No clear conclusions can be drawn about the superiority of CAD-CAM milling and 3D printing regarding denture accuracy. 10.1016/j.prosdent.2020.01.004
    Dental Pulp Stem Cells: Isolation, Characterization, Expansion, and Odontoblast Differentiation for Tissue Engineering. Dong Qing,Wang Yuanyuan,Mohabatpour Fatemeh,Zheng Li,Papagerakis Silvana,Chen Daniel,Papagerakis Petros Methods in molecular biology (Clifton, N.J.) Tissue engineering is an interdisciplinary area offering a promising approach by the use of stem cells combined with scaffolds and signaling factors for regeneration of damaged or lost tissues. Incorporation of a sufficient number of cells which do not elicit the immunoreaction in the body is a pivotal element for successful tissue formation using this method. Stem cells exhibiting strong capacity to self-renew and differentiate into different cell types are considered as a potent cell source. Among various cell sources, dental pulp stem cells (DPSCs) are widely under investigation due to the fact that they are simply obtainable from extracted third molars or orthodontically extracted teeth and show an excellent potential for clinical application and also their harvesting method is minimally invasive. DPSCs are odontogenic progenitor cells with clonogenic abilities, rapid proliferation rates, and multiple differentiation potentials. Here, we describe protocols that allow 1) the isolation of DPSCs from a single tooth; 2) the characterization of human mesenchymal stem cells markers of DPSCs by flow cytometry; 3) the culture growth of DPSCs in 2D (in cell culture flasks) and 3D (by 3D printing of cell-laden constructs); and 4) the in vivo evaluation of differentiation potential of DPSCs. 10.1007/978-1-4939-9012-2_9
    Periodontal Tissue Bioengineering: Is the Future Now? Fretwurst Tobias,Larsson Lena,Yu Shan Huey,Pilipchuk Sophia P,Kaigler Darnell,Giannobile William V Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995) Periodontitis affects nearly half of the adult population in the United States and leads to periodontium destruction, tooth loss, and tooth mobility. Novel bioengineering has become an area of interest in dentistry, as various approaches aim to regenerate attachment apparatus around diseased teeth with the use of barriers, scaffolds, bone grafts, or biologics. This article emphasizes recent findings in the fields of stem cell/gene therapy, 3-dimensional printing, and innovative scaffold designs for future applications in clinical care.
    Bioprinting of three-dimensional dentin-pulp complex with local differentiation of human dental pulp stem cells. Han Jonghyeuk,Kim Da Sol,Jang Ho,Kim Hyung-Ryong,Kang Hyun-Wook Journal of tissue engineering Numerous approaches have been introduced to regenerate artificial dental tissues. However, conventional approaches are limited when producing a construct with three-dimensional patient-specific shapes and compositions of heterogeneous dental tissue. In this research, bioprinting technology was applied to produce a three-dimensional dentin-pulp complex with patient-specific shapes by inducing localized differentiation of human dental pulp stem cells within a single structure. A fibrin-based bio-ink was designed for bioprinting with the human dental pulp stem cells. The effects of fibrinogen concentration within the bio-ink were investigated in terms of printability, human dental pulp stem cell compatibility, and differentiation. The results show that micro-patterns with human dental pulp stem cells could be achieved with more than 88% viability. Its odontogenic differentiation was also regulated according to the fibrinogen concentration. Based on these results, a dentin-pulp complex having patient-specific shape was produced by co-printing the human dental pulp stem cell-laden bio-inks with polycaprolactone, which is a bio-thermoplastic used for producing the overall shape. After culturing with differentiation medium for 15 days, localized differentiation of human dental pulp stem cells in the outer region of the three-dimensional cellular construct was successfully achieved with localized mineralization. This result demonstrates the possibility to produce patient-specific composite tissues for tooth tissue engineering using three-dimensional bioprinting technology. 10.1177/2041731419845849
    Vertical bone augmentation with 3D-synthetic monetite blocks in the rabbit calvaria. Torres Jesús,Tamimi Faleh,Alkhraisat Mohammad Hamdan,Prados-Frutos Juan Carlos,Rastikerdar Emad,Gbureck Uwe,Barralet Jake E,López-Cabarcos Enrique Journal of clinical periodontology INTRODUCTION:Long-term success of osteointegrated dental implants requires sufficient volume of healthy bone at the recipient sites. However, this is frequently lacking as a result of trauma, tooth loss, or infection. Onlay autografting is amongst the most predictable techniques for craniofacial vertical bone augmentation, however, complications related to donor site morbidity are common and alternatives to onlay autografts are desirable. AIM:To develop and evaluate a new synthetic onlay block for vertical bone augmentation. MATERIAL AND METHODS:Sixteen synthetic monetite monolithic discs-shaped blocks were prepared using a 3D-printing technique. The blocks were computer-designed, and had a diameter of 9.0 mm, a thickness of either 4.0 mm (n = 8) or 3.0 mm (n = 8) and one 0.5-mm wide central hole that enabled their surgical fixation with osteosynthesis screws. The blocks were randomly allocated to each side of the calvaria (right or left) of eight New Zealand rabbits and fixed with screws to achieve vertical bone augmentation. Eight weeks after the surgical intervention, the animals were sacrificed and the calvaria were retrieved for histological analysis. The following parameters were analysed: the interaction between the graft and the original bone surface, the amount of bone ingrowth within the graft and the gain in bone height achieved by the procedure. Wilcoxon t-test was used to evaluate significant differences between the two types of monetite bone block grafts. RESULTS:The blocks were easy to handle and no damage or fracture was registered while being screw-fixated to the calvarial bone. As a result, the surgical procedure was easy and quick. After a healing of 8 weeks, the synthetic blocks were strongly fused to the calvarial bone surface. Upon histological observation, the monetite blocks appeared to be infiltrated by newly formed bone, without histological signs of necrosis, osteolysis or foreign body reaction. Histomorphometry revealed that bone augmentation occurred within and over the monetite block. The 4.0- and 3.0-mm high blocks were filled with newly formed bone with 35% and 41% of their respective volumes. These observations indicated that craniofacial bone augmentations of at least 4 mm could be achieved with synthetic monetite blocks. CONCLUSION:Within the limits of our study, this novel material may be able to eliminate the need for autologous bone transplantation for the augmentation of large vertical bone defects. 10.1111/j.1600-051X.2011.01787.x
    Periodontal ligament stem/progenitor cells with protein-releasing scaffolds for cementum formation and integration on dentin surface. Cho Hankyu,Tarafder Solaiman,Fogge Michael,Kao Kristy,Lee Chang H Connective tissue research Purpose/Aim: Cementogenesis is a critical step in periodontal tissue regeneration given the essential role of cementum in anchoring teeth to the alveolar bone. This study is designed to achieve integrated cementum formation on the root surfaces of human teeth using growth factor-releasing scaffolds with periodontal ligament stem/progenitor cells (PDLSCs). MATERIALS AND METHODS:Human PDLSCs were sorted by CD146 expression, and characterized using CFU-F assay and induced multi-lineage differentiation. Polycaprolactone scaffolds were fabricated using 3D printing, embedded with poly(lactic-co-glycolic acids) (PLGA) microspheres encapsulating connective tissue growth factor (CTGF), bone morphogenetic protein-2 (BMP-2), or bone morphogenetic protein-7 (BMP-7). After removing cementum on human tooth roots, PDLSC-seeded scaffolds were placed on the exposed dentin surface. After 6-week culture with cementogenic/osteogenic medium, cementum formation and integration were evaluated by histomorphometric analysis, immunofluorescence, and qRT-PCR. RESULTS:Periodontal ligament (PDL) cells sorted by CD146 and single-cell clones show a superior clonogenecity and multipotency as compared with heterogeneous populations. After 6 weeks, all the growth factor-delivered groups showed resurfacing of dentin with a newly formed cementum-like layer as compared with control. BMP-2 and BMP-7 showed de novo formation of tissue layers significantly thicker than all the other groups, whereas CTGF and BMP-7 resulted in significantly improved integration on the dentin surface. The de novo mineralized tissue layer seen in BMP-7-treated samples expressed cementum matrix protein 1 (CEMP1). Consistently, BMP-7 showed a significant increase in CEMP1 mRNA expression. CONCLUSION:Our findings represent important progress in stem cell-based cementum regeneration as an essential part of periodontium regeneration. 10.1080/03008207.2016.1191478
    Image-based, fiber guiding scaffolds: a platform for regenerating tissue interfaces. Park Chan Ho,Rios Hector F,Taut Andrei D,Padial-Molina Miguel,Flanagan Colleen L,Pilipchuk Sophia P,Hollister Scott J,Giannobile William V Tissue engineering. Part C, Methods In the oral and craniofacial complex, tooth loss is the most commonly acquired disfiguring injury. Among the most formidable challenges of reconstructing tooth-supporting osseous defects in the oral cavity is the regeneration of functional multi-tissue complexes involving bone, ligament, and tooth cementum. Furthermore, periodontal multi-tissue engineering with spatiotemporal orientation of the periodontal ligament (PDL) remains the most challenging obstacle for restoration of physiological loading and homeostasis. We report on the ability of a hybrid computer-designed scaffold--developed utilizing computed tomography--to predictably facilitate the regeneration and integration of dental supporting tissues. Here, we provide the protocol for rapid prototyping, manufacture, surgical implantation, and evaluation of dual-architecture scaffolds for controlling fiber orientation and facilitating morphogenesis of bone-ligament complexes. In contrast to conventional single-system methods of fibrous tissue formation, our protocol supports rigorous control of multi-compartmental scaffold architecture using computational scaffold design and manufacturing by 3D printing, as well as the evaluation of newly regenerated tissue physiology for clinical implementation. 10.1089/ten.TEC.2013.0619
    Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells. Liu Jin,Ruan Jianping,Weir Michael D,Ren Ke,Schneider Abraham,Wang Ping,Oates Thomas W,Chang Xiaofeng,Xu Hockin H K Cells Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region. 10.3390/cells8060537
    Personalized scaffolding technologies for alveolar bone regenerative medicine. Yu Ning,Nguyen Trang,Cho Young D,Kavanagh Nolan M,Ghassib Iya,Giannobile William V Orthodontics & craniofacial research The reconstruction of alveolar bone defects associated with teeth and dental implants remains a clinical challenge in the treatment of patients affected by disease or injury of the alveolus. The aim of this review was to provide an overview on advances made in the use of personalized scaffolding technologies coupled with biologics, cells and gene therapies that offer future clinical applications for the treatment of patients requiring periodontal and alveolar bone regeneration. Over the past decade, advancements in three-dimensional (3D) imaging acquisition technologies such as cone-beam computed tomography (CBCT) and precise scaffold fabrication methods such as 3D bioprinting have resulted in personalized scaffolding constructs based on individual patient-specific anatomical data. Furthermore, 'fiber-guiding' scaffold designs utilize topographical cues to guide ligamentous fibers to form in orientation towards the root surface to improve tooth support. Therefore, a topic-focused literature search was conducted looking into fiber-guiding and image-based scaffolds and their associated clinical applications. 10.1111/ocr.12275
    A comparative study of the osteogenic performance between the hierarchical micro/submicro-textured 3D-printed Ti6Al4V surface and the SLA surface. Zhang Jinkai,Liu Jiaqiang,Wang Chengtao,Chen Fengshan,Wang Xudong,Lin Kaili Bioactive materials Three-dimensional (3D) printed titanium and its alloys have broad application prospect in the field of biomedical implant materials, although the biological performance of the original surface should be improved. Learning from the development experience of conventional titanium implants, to construct a hierarchical hybrid topological surface is the future direction of efforts. Since the original 3D-printed (3D hereafter) Ti6Al4V surface inherently has micron-scale features, in the present study, we introduced submicron-scale pits on the original surface by acid etching to obtain a hierarchical micro/submicro-textured surface. The characteristic and biological performance of the 3D-printed and acid-etched (3DA hereafter) surface were evaluated and compared with the conventional sandblasted, large-grit, acid-etched (SLA hereafter) surface. Our results suggested the adhesion, proliferation and osteogenic differentiation of bone marrow derived mesenchymal stromal cells (BMSCs), as well as the osseointegration on 3DA surfaces were significantly improved. However, the overall osteogenic performance of the 3DA surface was not as good as the conventional SLA surface. 10.1016/j.bioactmat.2019.12.008
    Progress and Challenges in Microengineering the Dental Pulp Vascular Microenvironment. Bertassoni Luiz E Journal of endodontics INTRODUCTION:The dental pulp is highly vascularized and innervated tissue that is uniquely designed, being highly biologically active, while being enclosed within the calcified structure of the tooth. It is well-established that the dental pulp vasculature is a key requirement for the functional performance of the tooth. Therefore, controlled regeneration of the dental pulp vasculature is a challenge that must be met for future regenerative endeavors in endodontics. METHODS:In this perspective review, we address recent progress and challenges on the use of microengineering methods and biomaterials scaffolds to fabricate the dental pulp vascular microenvironment. RESULTS:The conditions required to control the growth and differentiation of vascular capillaries are discussed, together with the conditions required for the formation of mature and stable pericyte-supported microvascular networks in 3-dimensional hydrogels and fabricated microchannels. Recent biofabrication methods, such as 3-dimensional bioprinting and micromolding are also discussed. Moreover, recent advances in the field of organs-on-a-chip are discussed regarding their applicability to dental research and endodontic regeneration. CONCLUSION:Collectively, this short review offers future directions in the field that are presented with the objective of pointing toward successful pathways for successful clinical and translational strategies in regenerative endodontics, with especial emphasis on the dental pulp vasculature. 10.1016/j.joen.2020.06.033
    A dentin-derived hydrogel bioink for 3D bioprinting of cell laden scaffolds for regenerative dentistry. Athirasala Avathamsa,Tahayeri Anthony,Thrivikraman Greeshma,França Cristiane M,Monteiro Nelson,Tran Victor,Ferracane Jack,Bertassoni Luiz E Biofabrication Recent studies in tissue engineering have adopted extracellular matrix (ECM) derived scaffolds as natural and cytocompatible microenvironments for tissue regeneration. The dentin matrix, specifically, has been shown to be associated with a host of soluble and insoluble signaling molecules that can promote odontogenesis. Here, we have developed a novel bioink, blending printable alginate (3% w/v) hydrogels with the soluble and insoluble fractions of the dentin matrix. We have optimized the printing parameters and the concentrations of the individual components of the bioink for print accuracy, cell viability and odontogenic potential. We find that, while viscosity, and hence printability of the bioinks, was greater in the formulations containing higher concentrations of alginate, a higher proportion of insoluble dentin matrix proteins significantly improved cell viability; where a 1:1 ratio of alginate and dentin (1:1 Alg-Dent) was most suitable. We further demonstrate high retention of the soluble dentin molecules within the 1:1 Alg-Dent hydrogel blends, evidencing renewed interactions between these molecules and the dentin matrix post crosslinking. Moreover, at concentrations of 100 μg ml, these soluble dentin molecules significantly enhanced odontogenic differentiation of stem cells from the apical papilla encapsulated in bioprinted hydrogels. In summary, the proposed novel bioinks have demonstrable cytocompatibility and natural odontogenic capacity, which can be a used to reproducibly fabricate scaffolds with complex three-dimensional microarchitectures for regenerative dentistry in the future. 10.1088/1758-5090/aa9b4e
    3D-printed custom trays with a Gothic arch for centric relation recording and definitive impression making for complete dentures: A dental technique. Qu Fang,Du Xue,Liu Wei-Cai The Journal of prosthetic dentistry An appliance was designed and fabricated by using computer-aided design and computer-aided manufacturing (CAD-CAM) and 3-dimensional (3D) printing to combine a custom tray with an intraoral Gothic arch. This helped simplify centric relation recording and combined definitive impression making and centric relation recording into a single step. 10.1016/j.prosdent.2018.01.021
    [Development of new technology in periodontal tissue engineering]. Yang X T,Yang B,Tian W D Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology The loss of periodontal support tissues might cause movement or finally loss of the teeth affected, impair furthermore the pronunciation and mastication functions, and even result in a series of physiological and psychological problems. Tissue engineering, as a technology to remodel missing tissues or organs and functional reconstruction, has achieved gratifying progress in regeneration of periodontal tissues. However, conventional construction methods have some deficiencies for functional periodontal reconstruction. In recent years, with the progress of tissue engineering technology, a series of new techniques and methods, such as cell sheet technology, decellular technology, electrospinning technology and three-dimensional printing, has been applied in tissue engineering bringing new hope for the regeneration of periodontal tissues. In this review article, the recent progress achieved in the field of periodontal tissue engineering and application of modern technology are summarized to make a brief exposition and to explore the future development of periodontal regeneration. 10.3760/cma.j.issn.1002-0098.2018.07.014
    [Three dimensional bioprinting technology of human dental pulp cells mixtures]. Xue Shi-hua,Lv Pei-jun,Wang Yong,Zhao Yu,Zhang Ting Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences OBJECTIVE:To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration. METHODS:Imageware 11.0 computer software was used to aid the design of the 3D biological printing blueprint. Sodium alginate-gelatin hydrosol was prepared and mixed with in vitro isolated hDPCs. The mixture contained 20 g/L sodium alginate and 80 g/L gelatin with cell density of 1×10(6)/mL. The bioprinting of hDPCs mixture was carried out according to certain parameters; the 3D constructs obtained by printing were examined; the viability of hDPCs after printing by staining the constructs with calcein-AM and propidium iodide dye and scanning of laser scanning confocal microscope was evaluated. The in vitro constructs obtained by the bioprinting were cultured, and the proliferation of hDPCs in the constructs detected. RESULTS:By using Imageware 11.0 software, the 3D constructs with the grid structure composed of the accumulation of staggered cylindrical microfilament layers were obtained. According to certain parameters, the hDPCs-sodium alginate-gelatin blends were printed by the 3D bioprinting technology. The self-defined shape and dimension of 3D constructs with the cell survival rate of 87%± 2% were constructed. The hDPCs could proliferate in 3D constructs after printing. CONCLUSION:In this study, the 3D bioprinting of hDPCs mixtures was realized, thus laying initial foundations for the application of the 3D bioprinting technology in tooth regeneration.
    Integration of 3D Printed and Micropatterned Polycaprolactone Scaffolds for Guidance of Oriented Collagenous Tissue Formation In Vivo. Pilipchuk Sophia P,Monje Alberto,Jiao Yizu,Hao Jie,Kruger Laura,Flanagan Colleen L,Hollister Scott J,Giannobile William V Advanced healthcare materials Scaffold design incorporating multiscale cues for clinically relevant, aligned tissue regeneration has potential to improve structural and functional integrity of multitissue interfaces. The objective of this preclinical study is to develop poly(ε-caprolactone) (PCL) scaffolds with mesoscale and microscale architectural cues specific to human ligament progenitor cells and assess their ability to form aligned bone-ligament-cementum complexes in vivo. PCL scaffolds are designed to integrate a 3D printed bone region with a micropatterned PCL thin film consisting of grooved pillars. The patterned film region is seeded with human ligament cells, fibroblasts transduced with bone morphogenetic protein-7 genes seeded within the bone region, and a tooth dentin segment positioned on the ligament region prior to subcutaneous implantation into a murine model. Results indicate increased tissue alignment in vivo using micropatterned PCL films, compared to random-porous PCL. At week 6, 30 μm groove depth significantly enhances oriented collagen fiber thickness, overall cell alignment, and nuclear elongation relative to 10 μm groove depth. This study demonstrates for the first time that scaffolds with combined hierarchical mesoscale and microscale features can align cells in vivo for oral tissue repair with potential for improving the regenerative response of other bone-ligament complexes. 10.1002/adhm.201500758
    Three-dimensional printed multiphase scaffolds for regeneration of periodontium complex. Lee Chang H,Hajibandeh Jeffrey,Suzuki Takahiro,Fan Andrew,Shang Peng,Mao Jeremy J Tissue engineering. Part A Tooth-supporting periodontium forms a complex with multiple tissues, including cementum, periodontal ligament (PDL), and alveolar bone. In this study, we developed multiphase region-specific microscaffolds with spatiotemporal delivery of bioactive cues for integrated periodontium regeneration. Polycarprolactione-hydroxylapatite (90:10 wt%) scaffolds were fabricated using three-dimensional printing seamlessly in three phases: 100-μm microchannels in Phase A designed for cementum/dentin interface, 600-μm microchannels in Phase B designed for the PDL, and 300-μm microchannels in Phase C designed for alveolar bone. Recombinant human amelogenin, connective tissue growth factor, and bone morphogenetic protein-2 were spatially delivered and time-released in Phases A, B, and C, respectively. Upon 4-week in vitro incubation separately with dental pulp stem/progenitor cells (DPSCs), PDL stem/progenitor cells (PDLSCs), or alveolar bone stem/progenitor cells (ABSCs), distinctive tissue phenotypes were formed with collagen I-rich fibers especially by PDLSCs and mineralized tissues by DPSCs, PDLSCs, and ABSCs. DPSC-seeded multiphase scaffolds upon in vivo implantation yielded aligned PDL-like collagen fibers that inserted into bone sialoprotein-positive bone-like tissue and putative cementum matrix protein 1-positive/dentin sialophosphoprotein-positive dentin/cementum tissues. These findings illustrate a strategy for the regeneration of multiphase periodontal tissues by spatiotemporal delivery of multiple proteins. A single stem/progenitor cell population appears to differentiate into putative dentin/cementum, PDL, and alveolar bone complex by scaffold's biophysical properties and spatially released bioactive cues. 10.1089/ten.TEA.2013.0386
    Three-Dimensional Custom-Root Replicate Tooth Dental Implants. Westover Brock Oral and maxillofacial surgery clinics of North America This article summarizes the accomplishments and knowledge gained over the past 2 decades with respect to immediate dental root analogue implants (RAIs). It discusses how the artificial nature of the present dental implant materials and unnatural shapes cause complications, posing a threat to long-term biointegration, and how RAIs will influence the way that implants are produced. Will an osseointegrated RAI be the optimal immediate replacement for extracted teeth in the future? How will three-dimensional printing be involved in these more biomimetic RAI systems? The present research and developments seem promising and will continue to shape the future of implant prosthodontics. 10.1016/j.coms.2019.03.010
    Three-dimensional printing biotechnology for the regeneration of the tooth and tooth-supporting tissues. Ma Yue,Xie Li,Yang Bo,Tian Weidong Biotechnology and bioengineering The tooth and its supporting tissues are organized with complex three-dimensional (3D) architecture, including the dental pulp with a blood supply and nerve tissues, complex multilayer periodontium, and highly aligned periodontal ligament (PDL). Mimicking such 3D complexity and the multicellular interactions naturally existing in dental structures represents great challenges in dental regeneration. Attempts to construct the complex system of the tooth and tooth-supporting apparatus (i.e., the PDL, alveolar bone, and cementum) have made certain progress owing to 3D printing biotechnology. Recent advances have enabled the 3D printing of biocompatible materials, seed cells, and supporting components into complex 3D functional living tissue. Furthermore, 3D bioprinting is driving major innovations in regenerative medicine, giving the field of regenerative dentistry a boost. The fabrication of scaffolds via 3D printing is already being performed extensively at the laboratory bench and in clinical trials; however, printing living cells and matrix materials together to produce tissue constructs by 3D bioprinting remains limited to the regeneration of dental pulp and the tooth germ. This review summarizes the application of scaffolds for cell seeding and biofabricated tissues via 3D printing and bioprinting, respectively, in the tooth and its supporting tissues. Additionally, the key advantages and prospects of 3D bioprinting in regenerative dentistry are highlighted, providing new ideas for dental regeneration. 10.1002/bit.26882