Regenerative endodontics: a review of current status and a call for action.

Millions of teeth are saved each year by root canal therapy. Although current treatment modalities offer high levels of success for many conditions, an ideal form of therapy might consist of regenerative approaches in which diseased or necrotic pulp tissues are removed and replaced with healthy pulp tissue to revitalize teeth. Researchers are working toward this objective. Regenerative endodontics is the creation and delivery of tissues to replace diseased, missing, and traumatized pulp. This review provides an overview of regenerative endodontics and its goals, and describes possible techniques that will allow regenerative endodontics to become a reality. These potential approaches include root-canal revascularization, postnatal (adult) stem cell therapy, pulp implant, scaffold implant, three-dimensional cell printing, injectable scaffolds, and gene therapy. These regenerative endodontic techniques will possibly involve some combination of disinfection or debridement of infected root canal systems with apical enlargement to permit revascularization and use of adult stem cells, scaffolds, and growth factors. Although the challenges of introducing endodontic tissue engineering therapies are substantial, the potential benefits to patients and the profession are equally ground breaking. Patient demand is staggering both in scope and cost, because tissue engineering therapy offers the possibility of restoring natural function instead of surgical placement of an artificial prosthesis. By providing an overview of the methodological issues required to develop potential regenerative endodontic therapies, we hope to present a call for action to develop these therapies for clinical use.

[1]  K Petersson,et al.  Evaluation of the ability of thermal and electrical tests to register pulp vitality. , 1999, Endodontics & dental traumatology.

[2]  R. Hall,et al.  Transforming Growth Factor-β1 (TGF-β1) in dentine matrix , 1998 .

[3]  I. Rotstein,et al.  Endodontic treatment outcomes in a large patient population in the USA: an epidemiological study. , 2004, Journal of endodontics.

[4]  V. Terranova,et al.  Repopulation of dentin surfaces by periodontal ligament cells and endothelial cells. Effect of basic fibroblast growth factor. , 1989, Journal of periodontology.

[5]  A. Sigurdsson,et al.  Pulp revascularization of replanted immature dog teeth after treatment with minocycline and doxycycline assessed by laser Doppler flowmetry, radiography, and histology. , 2004, Dental traumatology : official publication of International Association for Dental Traumatology.

[6]  T. Yamamura Differentiation of Pulpal Cells and Inductive Influences of Various Matrices with Reference to Pulpal Wound Healing , 1985, Journal of dental research.

[7]  Aylin Sendemir-Urkmez,et al.  Evaluation of vacuum and dynamic cell seeding of polyglycolic acid and chitosan scaffolds for cartilage engineering. , 2005, American journal of veterinary research.

[8]  M. Nakashima Tissue engineering in endodontics. , 2005, Australian endodontic journal : the journal of the Australian Society of Endodontology Inc.

[9]  Z. Estrov,et al.  Umbilical cord blood-derived cells for tissue repair. , 2005, Cytotherapy.

[10]  M. Iwaku,et al.  Sterilization of infected root-canal dentine by topical application of a mixture of ciprofloxacin, metronidazole and minocycline in situ. , 1996, International endodontic journal.

[11]  H. Blau,et al.  Optimizing Techniques for Tracking Transplanted Stem Cells In Vivo , 2005, Stem cells.

[12]  A. Akamine,et al.  Dentin Regeneration by Dental Pulp Stem Cell Therapy with Recombinant Human Bone Morphogenetic Protein 2 , 2004, Journal of dental research.

[13]  M. Goldberg,et al.  Pulpo-dentinal complex revisited. , 1995, Journal of dentistry.

[14]  A. Smith,et al.  Angiogenic growth factors in human dentine matrix. , 2000, Archives of oral biology.

[15]  M. Czonstkowsky,et al.  The smear layer in endodontics. , 1990, Dental clinics of North America.

[16]  Y. Tabata Nanomaterials of drug delivery systems for tissue regeneration. , 2005, Methods in molecular biology.

[17]  Thomas Boland,et al.  Rapid prototyping of tissue-engineering constructs, using photopolymerizable hydrogels and stereolithography. , 2004, Tissue engineering.

[18]  J A Barron,et al.  Biological Laser Printing: A Novel Technique for Creating Heterogeneous 3-dimensional Cell Patterns , 2004, Biomedical microdevices.

[19]  S. Llames,et al.  Human plasma as a dermal scaffold for the generation of a completely autologous bioengineered skin , 2004, Transplantation.

[20]  A. Smith,et al.  Embryo-derived stem cells: of mice and men. , 2001, Annual review of cell and developmental biology.

[21]  A. Salgado,et al.  Nano- and micro-fiber combined scaffolds: A new architecture for bone tissue engineering , 2005, Journal of materials science. Materials in medicine.

[22]  R. Genco,et al.  Tetracycline and its derivatives strongly bind to and are released from the tooth surface in active form. , 1983, Journal of periodontology.

[23]  J. Elisseeff,et al.  Advances in skeletal tissue engineering with hydrogels. , 2005, Orthodontics & craniofacial research.

[24]  Wei-Shou Hu,et al.  Culture systems for pluripotent stem cells. , 2005, Journal of bioscience and bioengineering.

[25]  Dhirendra S Katti,et al.  Growth factor-delivery systems for tissue engineering: a materials perspective , 2006, Expert review of medical devices.

[26]  S. Shi,et al.  Recovery of Stem Cells from Cryopreserved Periodontal Ligament , 2005, Journal of dental research.

[27]  M. Trope,et al.  Pulp revascularization of replanted immature dog teeth after different treatment methods. , 2000, Endodontics & dental traumatology.

[28]  J. B. Bogardus,et al.  Solubility of doxycycline in aqueous solution. , 1979, Journal of pharmaceutical sciences.

[29]  G. Schmalz Use of cell cultures for toxicity testing of dental materials--advantages and limitations. , 1994, Journal of dentistry.

[30]  J. Kronman,et al.  The efficacy of several irrigating solutions for endodontics: a scanning electron microscopic study. , 1981, Oral surgery, oral medicine, and oral pathology.

[31]  Peter J. Donovan,et al.  Derivation of pluripotent stem cells from cultured human primordial germ cells , 1998 .

[32]  I. Mejàre,et al.  Rate and predictability of pulp revascularization in therapeutically reimplanted permanent incisors. , 1986, Endodontics & dental traumatology.

[33]  Stan Gronthos,et al.  SHED: Stem cells from human exfoliated deciduous teeth , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  K. Kusumoto,et al.  Experimental studies on bone inducing activity of composites of atelopeptide type I collagen as a carrier for ectopic osteoinduction by rhBMP-2. , 1995, Biochemical and biophysical research communications.

[36]  Marcus Textor,et al.  An inverted microcontact printing method on topographically structured polystyrene chips for arrayed micro-3-D culturing of single cells. , 2005, Biomaterials.

[37]  S. Gronthos,et al.  The efficacy of mesenchymal stem cells to regenerate and repair dental structures. , 2005, Orthodontics & craniofacial research.

[38]  D. Gospodarowicz Purification of a fibroblast growth factor from bovine pituitary. , 1975, The Journal of biological chemistry.

[39]  M. Valera,et al.  Smear layer removal capacity of disinfectant solutions used with and without EDTA for the irrigation of canals: a SEM study. , 2003, Pesquisa odontologica brasileira = Brazilian oral research.

[40]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[41]  B. Ligon Thomas Huckle Weller MD: Nobel Laureate and research pioneer in poliomyelitis, varicella-zoster virus, cytomegalovirus, rubella, and other infectious diseases. , 2002, Seminars in pediatric infectious diseases.

[42]  M. Rao Stem sense: a proposal for the classification of stem cells. , 2004, Stem cells and development.

[43]  Pierre Weiss,et al.  Three-dimensional culture and differentiation of human osteogenic cells in an injectable hydroxypropylmethylcellulose hydrogel. , 2005, Biomaterials.

[44]  Ruch Jv Patterned distribution of differentiating dental cells: facts and hypotheses. , 1990 .

[45]  Ivan Martin,et al.  In vitro differentiation of chick embryo bone marrow stromal cells into cartilaginous and bone‐like tissues , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[46]  Robert Langer,et al.  In vivo engineering of organs: the bone bioreactor. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[47]  F. Gage,et al.  In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector , 1996, Science.

[48]  E. Sachlos,et al.  Making tissue engineering scaffolds work. Review: the application of solid freeform fabrication technology to the production of tissue engineering scaffolds. , 2003, European cells & materials.

[49]  F. Guilak,et al.  Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. , 2003, Cytotherapy.

[50]  Seong-Jin Kim,et al.  Hyaline cartilage regeneration using mixed human chondrocytes and transforming growth factor-beta1- producing chondrocytes. , 2005, Tissue engineering.

[51]  D. Tziafas Basic mechanisms of cytodifferentiation and dentinogenesis during dental pulp repair. , 1995, The International journal of developmental biology.

[52]  R. Rutherford,et al.  Stimulation of the rat dentine-pulp complex by bone morphogenetic protein-7 in vitro. , 2000, Archives of oral biology.

[53]  R. Ewers,et al.  HA/TCP compounding of a porous CaP biomaterial improves bone formation and scaffold degradation--a long-term histological study. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[54]  C. Verfaillie,et al.  Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. , 2001, Blood.

[55]  Mahmoud Torabinejad,et al.  Evaluation of cytotoxicity of MTAD using the MTT-tetrazolium method. , 2003, Journal of endodontics.

[56]  B. Atiyeh,et al.  New technologies for burn wound closure and healing--review of the literature. , 2005, Burns : journal of the International Society for Burn Injuries.

[57]  M. Trope,et al.  Revascularization of immature permanent teeth with apical periodontitis: new treatment protocol? , 2004, Journal of endodontics.

[58]  N. Skaug,et al.  Tetracycline-impregnated enamel and dentin: duration of antimicrobial capacity. , 1985, Scandinavian journal of dental research.

[59]  M. Goldberg,et al.  Osteogenic proteins (bone sialoprotein and bone morphogenetic protein-7) and dental pulp mineralization , 2002, Journal of materials science. Materials in medicine.

[60]  R. Pettengell,et al.  Autologous stem cell transplantation in follicular non-Hodgkin's lymphoma , 2002, Bone Marrow Transplantation.

[61]  Amler Mh The age factor in human extraction wound healing. , 1977 .

[62]  J. Mao,et al.  Stem cell‐based composite tissue constructs for regenerative medicine , 2005, Biotechnology and bioengineering.

[63]  S. Shibata,et al.  Short-term dentin bridging of mechanically-exposed pulps capped with adhesive resin systems. , 2000, Operative dentistry.

[64]  A. Morgunkova The p53 Gene Family: Control of Cell Proliferation and Developmental Programs , 2005, Biochemistry (Moscow).

[65]  P. Schmidlin,et al.  Chelation in root canal therapy reconsidered. , 2005, Journal of endodontics.

[66]  M. Nakashima Induction of Dentin Formation on Canine Amputated Pulp by Recombinant Human Bone Morphogenetic Proteins (BMP)-2 and -4 , 1994, Journal of dental research.

[67]  K. Hargreaves,et al.  Epidemiological evaluation of the outcomes of nonsurgical root canal treatment in a large cohort of insured dental patients. , 2001, Journal of endodontics.

[68]  M Nakashima,et al.  Induction of dentine in amputated pulp of dogs by recombinant human bone morphogenetic proteins-2 and -4 with collagen matrix. , 1994, Archives of oral biology.

[69]  S. Friedman,et al.  The success of endodontic therapy--healing and functionality. , 2004, Journal of the California Dental Association.

[70]  W. Kuhl Die Zellelemente in der Leibeshöhlenflüssigkeit des Seeigels Psammechinus miliaris (Gmel.) und ihr bewegungsphysiologisches Verhalten , 2004, Zeitschrift für Zellforschung und Mikroskopische Anatomie.

[71]  Rakesh K. Jain,et al.  Interstitial pH and pO2 gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation , 1997, Nature Medicine.

[72]  J. Wozney,et al.  Expression patterns of bone morphogenetic proteins (Bmps) in the developing mouse tooth suggest roles in morphogenesis and cell differentiation , 1997, Developmental dynamics : an official publication of the American Association of Anatomists.

[73]  A. Boyde,et al.  Stem Cell Properties of Human Dental Pulp Stem Cells , 2002, Journal of dental research.

[74]  D. Clewell,et al.  Virulence, phenotype and genotype characteristics of endodontic Enterococcus spp. , 2005, Oral microbiology and immunology.

[75]  J. Riviere,et al.  Pharmacology and toxicology of doxycycline. , 1988, Veterinary and human toxicology.

[76]  M. Brännström Smear layer: pathological and treatment considerations. , 1984, Operative dentistry. Supplement.

[77]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[78]  J. V. von Fraunhofer,et al.  Fracture resistance of human root dentin exposed to intracanal calcium hydroxide. , 2005, Journal of endodontics.

[79]  J. Hillman Genetically modified Streptococcus mutans for the prevention of dental caries. , 2002 .

[80]  Patrick L. Taylor The gap between law and ethics in human embryonic stem cell research: Overcoming the effect of U.S. Federal policy on research advances and public benefit , 2005, Science and engineering ethics.

[81]  R. Rutherford,et al.  Treatment of inflamed ferret dental pulps with recombinant bone morphogenetic protein-7. , 2000, European journal of oral sciences.

[82]  T. Albert,et al.  Differentiation of Mesenchymal Stem Cells Towards a Nucleus Pulposus-like Phenotype In Vitro: Implications for Cell-Based Transplantation Therapy , 2004, Spine.

[83]  M. Trope,et al.  Antimicrobial and toxic effects of established and potential root canal irrigants. , 1995, Journal of endodontics.

[84]  M J Yaszemski,et al.  Polymer concepts in tissue engineering. , 1998, Journal of biomedical materials research.

[85]  S. Sato,et al.  Mineralized nodule formation by cultures of human dental pulp-derived fibroblasts. , 1992, Archives of oral biology.

[86]  Anthony J. Smith,et al.  Saving Pulps—A Biological Basis. An Overview , 2002, Primary dental care : journal of the Faculty of General Dental Practitioners.

[87]  K. Wilson,et al.  The cost of allogeneic red blood cells – a systematic review , 2003, Transfusion medicine.

[88]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[89]  Robert Langer,et al.  Biodegradable Polymer Scaffolds for Tissue Engineering , 1994, Bio/Technology.

[90]  R. Poulsom,et al.  Adult stem cell plasticity , 2002, The Journal of pathology.

[91]  P. Wesselink,et al.  The smear layer: a phenomenon in root canal therapy. , 1995, International endodontic journal.

[92]  F. Desgrandchamps Biomaterials in functional reconstruction , 2000, Current opinion in urology.

[93]  S. Iwaya,et al.  Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. , 2001, Dental traumatology : official publication of International Association for Dental Traumatology.

[94]  J. Feit,et al.  Incorporation of 3H Thymidine into Damaged Pulp of Rat Incisors , 1970, Journal of dental research.

[95]  Joo L. Ong,et al.  Diffusion in Musculoskeletal Tissue Engineering Scaffolds: Design Issues Related to Porosity, Permeability, Architecture, and Nutrient Mixing , 2004, Annals of Biomedical Engineering.

[96]  R. Oringer Biological mediators for periodontal and bone regeneration. , 2002, Compendium of continuing education in dentistry.

[97]  K. Matsumoto,et al.  A comparative study of the removal of smear layer by three endodontic irrigants and two types of laser. , 1999, International endodontic journal.

[98]  B. Baum,et al.  Developing a convenient large animal model for gene transfer to salivary glands in vivo , 2004, The journal of gene medicine.

[99]  P. Menasché The potential of embryonic stem cells to treat heart disease. , 2005, Current opinion in molecular therapeutics.

[100]  S. Hofer,et al.  The use of pimonidazole to characterise hypoxia in the internal environment of an in vivo tissue engineering chamber. , 2005, British journal of plastic surgery.

[101]  G. Demetri,et al.  Clinical Applications of Cytokines and Growth Factors , 1999, Developments in Oncology.

[102]  E. Kraszewska,et al.  Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells in leukapheresis product and bone marrow for clinical transplantation: a comparison of three methods. , 2006, Folia histochemica et cytobiologica.

[103]  M. Torabinejad,et al.  A new solution for the removal of the smear layer. , 2003, Journal of endodontics.

[104]  H. F. Ross,et al.  Tooth slice organ culture for cytotoxicity assessment of dental materials. , 2000, Biomaterials.

[105]  E. Hoshino,et al.  In vitro antimicrobial susceptibility to combinations of drugs on bacteria from carious and endodontic lesions of human deciduous teeth. , 1993, Oral microbiology and immunology.

[106]  H. Sung,et al.  Tissue regeneration observed in a porous acellular bovine pericardium used to repair a myocardial defect in the right ventricle of a rat model. , 2005, The Journal of thoracic and cardiovascular surgery.

[107]  W. Murphy,et al.  New strategies for preventing graft-versus-host disease. , 1999, Current opinion in immunology.

[108]  G. Heden,et al.  Enamel matrix derivative (EMDOGAIN) in the treatment of intrabony periodontal defects. , 1997, Journal of clinical periodontology.

[109]  F. García-Godoy,et al.  The outlook for implants and endodontics: a review of the tissue engineering strategies to create replacement teeth for patients. , 2006, Dental clinics of North America.

[110]  G. T. Huang,et al.  In vitro characterization of human dental pulp cells: various isolation methods and culturing environments , 2006, Cell and Tissue Research.

[111]  S. Valiante,et al.  An approachable human adult stem cell source for hard‐tissue engineering , 2006, Journal of cellular physiology.

[112]  L. Fortier Stem cells: classifications, controversies, and clinical applications. , 2005, Veterinary surgery : VS.

[113]  R. Rutherford BMP-7 gene transfer to inflamed ferret dental pulps. , 2001, European journal of oral sciences.

[114]  L. Spångberg,et al.  Molecular detection of Enterococcus species in root canals of therapy-resistant endodontic infections. , 2005, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[115]  O. Ringdén,et al.  Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[116]  B. Clarkson,et al.  In vitro differentiation and mineralization of human dental pulp cells induced by dentin extract , 2005, In Vitro Cellular & Developmental Biology - Animal.

[117]  V. Kindler Postnatal stem cell survival: does the niche, a rare harbor where to resist the ebb tide of differentiation, also provide lineage-specific instructions? , 2005, Journal of leukocyte biology.

[118]  Zhi Ding,et al.  Porous chitosan-gelatin scaffold containing plasmid DNA encoding transforming growth factor-beta1 for chondrocytes proliferation. , 2006, Biomaterials.

[119]  Jeremy J Mao,et al.  Tissue-engineered osteochondral constructs in the shape of an articular condyle. , 2005, The Journal of bone and joint surgery. American volume.

[120]  T P van der Burgt,et al.  Tooth discoloration induced by endodontic sealers. , 1986, Oral surgery, oral medicine, and oral pathology.

[121]  A. Akamine,et al.  The application of tissue engineering to regeneration of pulp and dentin in endodontics. , 2005, Journal of endodontics.

[122]  L. Windsor,et al.  Histomorphometric analysis of odontoblast-like cell numbers and dentine bridge secretory activity following pulp exposure. , 2003, International endodontic journal.

[123]  S. Schwartz,et al.  nterococcus faecalis: Its Role in Root Canal Treatment ailure and Current Concepts in Retreatment , 2006 .

[124]  C. M. Agrawal,et al.  Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers. , 1996, Biomaterials.

[125]  M. Reynolds,et al.  Alveolar ridge and sinus augmentation utilizing platelet-rich plasma in combination with freeze-dried bone allograft: case series. , 2000, Journal of periodontology.

[126]  L. A. Silva,et al.  In vivo antimicrobial activity of 2% chlorhexidine used as a root canal irrigating solution. , 1999, Journal of endodontics.

[127]  B. Baum,et al.  The impact of gene therapy on dentistry. , 1995, Journal of the American Dental Association.

[128]  Bradley R. Ringeisen,et al.  Laser Printing of Single Cells: Statistical Analysis, Cell Viability, and Stress , 2005, Annals of Biomedical Engineering.

[129]  P. Laurent,et al.  Activation of human dental pulp progenitor/stem cells in response to odontoblast injury. , 2005, Archives of oral biology.

[130]  William H. Eaglstein,et al.  Tissue-Engineered Skin , 2001 .

[131]  I. Mjör,et al.  Healing of pulp exposures: an ultrastructural study. , 1991, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[132]  R. Gardner,et al.  Stem cells: potency, plasticity and public perception * , 2002, Journal of anatomy.

[133]  D J Mooney,et al.  Bone Regeneration via a Mineral Substrate and Induced Angiogenesis , 2004, Journal of dental research.

[134]  A. Reddi,et al.  The application of bone morphogenetic proteins to dental tissue engineering , 2003, Nature Biotechnology.

[135]  Y. Yamada,et al.  Regulatory role of transforming growth factor-beta, bone morphogenetic protein-2, and protein-4 on gene expression of extracellular matrix proteins and differentiation of dental pulp cells. , 1994, Developmental biology.

[136]  O. Zekioğlu,et al.  Comparison of antibacterial and toxic effects of various root canal irrigants. , 2003, International endodontic journal.

[137]  A. Sloan,et al.  Stimulation of the dentine-pulp complex of rat incisor teeth by transforming growth factor-beta isoforms 1-3 in vitro. , 1999, Archives of oral biology.

[138]  W. Gullick,et al.  The epidermal growth factor receptor family. , 2005, Endocrine-related cancer.

[139]  Jianwen Cai,et al.  Root canal filled versus non-root canal filled teeth: a retrospective comparison of survival times. , 2005, Journal of public health dentistry.

[140]  C. Patrick,et al.  Microvascular endothelial cells sustain preadipocyte viability under hypoxic conditions , 2005, In Vitro Cellular & Developmental Biology - Animal.

[141]  N. Stott,et al.  Gene therapy in orthopaedic surgery: the current status , 2004, ANZ journal of surgery.

[142]  M. Harmsen,et al.  The enzymatic degradation of scaffolds and their replacement by vascularized extracellular matrix in the murine myocardium. , 2006, Biomaterials.

[143]  Sawyer B. Fuller,et al.  A fast flexible ink-jet printing method for patterning dissociated neurons in culture , 2004, Journal of Neuroscience Methods.

[144]  D. Chiego,et al.  Autoradiographic analysis of odontoblast replacement following pulp exposure in primate teeth. , 1990, Archives of oral biology.

[145]  Aldo R Boccaccini,et al.  Bioactive composite materials for tissue engineering scaffolds , 2005, Expert review of medical devices.

[146]  M. Doser,et al.  Encapsulation of Islets in Rough Surface, Hydroxymethylated Polysulfone Capillaries Stimulates VEGF Release and Promotes Vascularization after Transplantation , 2005, Cell transplantation.

[147]  M. Block,et al.  Anterior maxillary advancement using tooth-supported distraction osteogenesis. , 1995, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[148]  J. Raguse,et al.  A metabolically active dermal replacement (Dermagraft) for vestibuloplasty. , 2005, Journal of oral rehabilitation.

[149]  Mahmoud Torabinejad,et al.  Clinical implications of the smear layer in endodontics: a review. , 2002, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[150]  Cyntia R A Estrela,et al.  Control of microorganisms in vitro by endodontic irrigants. , 2003, Brazilian dental journal.

[151]  S. Dimmeler,et al.  Neovascularization and cardiac repair by bone marrow-derived stem cells. , 2006, Handbook of experimental pharmacology.

[152]  A. Kaufman,et al.  Hypersensitivity to sodium hypochlorite. , 1989, Journal of endodontics.

[153]  M. Nakashima Bone morphogenetic proteins in dentin regeneration for potential use in endodontic therapy. , 2005, Cytokine & growth factor reviews.

[154]  P. Yelick,et al.  Tissue Engineering of Complex Tooth Structures on Biodegradable Polymer Scaffolds , 2002, Journal of dental research.

[155]  W. Hitzig,et al.  Bone marrow transplantation for severe combined immunodeficiency disease , 1979, European Journal of Pediatrics.

[156]  S. Watt,et al.  Exploitation of stem cell plasticity , 2003, Transfusion medicine.

[157]  D. Mooney,et al.  Tissue engineering's impact on dentistry. , 2001, Journal of dental education.

[158]  K. Sartor,et al.  Quantitative analysis of MRI signal intensity as a tool for evaluating tooth pulp vitality. , 2004, Dento maxillo facial radiology.

[159]  J. Leeton,et al.  The search for donor eggs: a problem of supply and demand. , 1986, Clinical reproduction and fertility.

[160]  Hermann Bw On the reaction of the dental pulp to vital amputation and calxyl capping , 1952 .

[161]  A. Akamine,et al.  Stimulation of reparative dentin formation by ex vivo gene therapy using dental pulp stem cells electrotransfected with growth/differentiation factor 11 (Gdf11). , 2004, Human gene therapy.

[162]  H. Lesot,et al.  Facts and hypotheses concerning the control of odontoblast differentiation. , 1982, Differentiation; research in biological diversity.

[163]  Ying Luo,et al.  A photolabile hydrogel for guided three-dimensional cell growth and migration , 2004, Nature materials.

[164]  A. Flyvbjerg,et al.  Pulp-capping with Recombinant Human Insulin- like Growth Factor I (rhIGF-I) in Rat Molars , 2001, Advances in dental research.

[165]  H. Lesot,et al.  Induction of odontoblast-like cell differentiation in dog dental pulps after in vivo implantation of dentine matrix components. , 1995, Archives of oral biology.

[166]  L. Guenin A failed noncomplicity scheme. , 2004, Stem cells and development.

[167]  Ali Khademhosseini,et al.  Micropatterned cell co-cultures using layer-by-layer deposition of extracellular matrix components. , 2006, Biomaterials.

[168]  D. Mccarthy,et al.  Bone marrow transplantation for genetic disorders. , 1990, Blood reviews.

[169]  W. Wilkison,et al.  Neurogenic differentiation of murine and human adipose-derived stromal cells. , 2002, Biochemical and biophysical research communications.

[170]  Rule Dc,et al.  Root growth and apical repair subsequent to pulpal necrosis in children. , 1966 .

[171]  H. Mizuno,et al.  Mesengenic potential and future clinical perspective of human processed lipoaspirate cells. , 2003, Journal of Nippon Medical School = Nippon Ika Daigaku zasshi.

[172]  S. Gronthos,et al.  Perivascular Niche of Postnatal Mesenchymal Stem Cells in Human Bone Marrow and Dental Pulp , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[173]  K. Bessho,et al.  Acceleration effect of human recombinant bone morphogenetic protein-2 on differentiation of human pulp cells into odontoblasts. , 2004, Journal of endodontics.

[174]  A. Plasschaert,et al.  Tooth discoloration induced by dental materials. , 1985, Oral surgery, oral medicine, and oral pathology.

[175]  M. Iwaku,et al.  In-vitro antibacterial susceptibility of bacteria taken from infected root dentine to a mixture of ciprofloxacin, metronidazole and minocycline. , 1996, International endodontic journal.

[176]  M. Torabinejad,et al.  Effect of MTAD on Enterococcus faecalis-contaminated root canals of extracted human teeth. , 2003, Journal of endodontics.

[177]  Bruce J Baum Biomedical research, oral medicine, and the future. , 2002, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[178]  M. Rossi,et al.  Scanning electron microscopic study of the cleaning ability of chlorhexidine as a root-canal irrigant. , 2003, International endodontic journal.

[179]  S. Ramakrishna,et al.  Applications of polymer nanofibers in biomedicine and biotechnology , 2005, Applied biochemistry and biotechnology.

[180]  D. Mooney,et al.  The impact of tissue engineering on dentistry. , 2000, Journal of the American Dental Association.

[181]  R. White,et al.  A comparison of 2.0% chlorhexidine gluconate and 5.25% sodium hypochlorite as antimicrobial endodontic irrigants. , 1994, Journal of endodontics.

[182]  F. García-Godoy,et al.  Stem cell responses in tooth regeneration. , 2004, Stem cells and development.

[183]  Richard Heller,et al.  Electroporation for targeted gene transfer , 2005, Expert opinion on drug delivery.

[184]  M. Fitzgerald Cellular Mechanics of Dentinal Bridge Repair Using 3H-Thymidine , 1979, Journal of dental research.

[185]  U. Ripamonti,et al.  Tissue engineering: TGF-β superfamily members and delivery systems in bone regeneration , 2002, Expert Reviews in Molecular Medicine.

[186]  M. Torabinejad,et al.  The effect of various concentrations of sodium hypochlorite on the ability of MTAD to remove the smear layer. , 2003, Journal of endodontics.

[187]  P. Yelick,et al.  Bioengineered Teeth from Cultured Rat Tooth Bud Cells , 2004, Journal of dental research.

[188]  J. B. Matthews,et al.  Trans-dentinal Stimulation of Tertiary Dentinogenesis , 2001, Advances in dental research.

[189]  R. Emshoff,et al.  Assessing revascularization of avulsed permanent maxillary incisors by laser Doppler flowmetry. , 2003, Journal of the American Dental Association.

[190]  L. Akard,et al.  Peripheral blood progenitor cell transplantation. , 2002, Therapeutic apheresis : official journal of the International Society for Apheresis and the Japanese Society for Apheresis.

[191]  Yasuhiko Tabata,et al.  Tissue regeneration based on growth factor release. , 2003, Tissue engineering.

[192]  T. Silva,et al.  Dentin matrix proteins and soluble factors: intrinsic regulatory signals for healing and resorption of dental and periodontal tissues? , 2004, Oral diseases.

[193]  A. U. Daniels,et al.  Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products. , 1994, Journal of applied biomaterials : an official journal of the Society for Biomaterials.

[194]  D. Costea,et al.  The phenotype of in vitro reconstituted normal human oral epithelium is essentially determined by culture medium. , 2005, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[195]  Y. Shimabukuro,et al.  Periodontal Regeneration by Fgf-2 (bfgf) in Primate Models on Behalf Of: International and American Associations for Dental Research Periodontal Regeneration by Fgf-2 (bfgf) in Primate Models , 2001 .

[196]  J. Roulet,et al.  Pulp capping of carious exposures: treatment outcome after 5 and 10 years: a retrospective study. , 2000, Journal of endodontics.

[197]  I. About,et al.  Cavity remaining dentin thickness and pulpal activity. , 2002, American journal of dentistry.