This study investigated tooth and periodontal regeneration through cell homing without cell transplantation. Novel anatomically shaped scaffolds for rat incisors and human molars were fabricated using 3D bioprinting of poly-ε-caprolactone and hydroxyapatite with microchannels. The scaffolds were implanted either orthotopically into rat incisor extraction sockets or ectopically under rat skin. Stromal-derived factor-1 and bone morphogenetic protein-7 delivered in the microchannels recruited endogenous cells and blood vessels. After 9 weeks, new bone and a structure resembling the periodontal ligament regenerated at the interface of the rat incisor scaffold with native bone. The human molar scaffolds also
This document summarizes research on osseointegration conducted by Per-Ingvar Brinemark and collaborators since 1952. Their experimental studies in animals analyzed tissue response to implanted titanium fixtures and developed techniques for reconstructing bone defects using grafts stabilized by integrated fixtures. This led to applying osseointegration clinically in 1965 to anchor dental prostheses via titanium implants integrated directly into jawbones, providing stable long-term function without intermediate soft tissues. Their research established osseointegration as a viable method for reconstructing edentulous jaws and anchoring prostheses.
The document summarizes a study that investigated the structural and mechanical properties of human jaw bone attached to a tooth. Specifically, it examined "bundle bone", a type of adapted bone found in the jaw. Nanoscale imaging revealed bundle bone has a higher concentration of minerals and a higher elastic modulus than normal jaw bone. This suggests the adaptations in bundle bone allow it to better withstand forces from tooth movement and maintain the function of the bone-tooth complex joint. Understanding these adaptations could help address clinical issues like malocclusion and periodontal disease.
In this study, Static structural analysis of a molar tooth was performed by using FEM. The commercial finite element package ANSYS version 14.5 was used for the solution of the problem. The molars or molar teeth are large, flat teeth at the back of the mouth. They are more developed in mammals. They are used primarily to grind food during chewing. Sometimes we are using artificial teeth instead of human molar tooth during broken. Here we optimize the molar teeth using different materials like acrylic, porcelain, silver and zirconia. Taking into consideration of forces acting on the top of the first molar teeth, the deformation, strain and stress are tabulated. And here we are studying about the molar teeth.
This document discusses biomaterials with both antimicrobial and osteoinductive properties that can be applied to spinal surgery. It summarizes various biomaterials and drugs that have these properties, including nanosilver, quaternized chitosan, copper ions, and bone morphogenetic proteins (BMPs). It also discusses different methods for delivering both antimicrobial and osteoinductive drugs from biomaterials, including surface adsorption, co-encapsulation, and surface coatings. The goal is to develop materials that can simultaneously deliver these drugs to repair infected bone defects.
The documents discuss various factors that influence bone regeneration, including osteogenic cells, osteoconductive scaffolds, growth factors, and the mechanical environment. Optimal bone regeneration requires an environment that supports osteoprogenitor cell recruitment, proliferation and differentiation, angiogenesis, and extracellular matrix formation. A variety of graft materials and their properties are reviewed in relation to supporting bone healing and regeneration.
This document discusses guided tissue regeneration (GTR) for treating endodontic-periodontal lesions. It describes that GTR involves placing a barrier membrane to prevent non-bone cells from migrating first to the root surface. The success rate of treating these lesions without GTR is only 27-37%, but increases to 95% with GTR. A case example is provided of a patient with a deep periodontal pocket and bone loss treated with root canal therapy, scaling and root planing, and later GTR using an autogenous bone graft and membrane. Radiographs alone are not reliable for assessing bone fill after surgery.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
This study used finite element analysis to analyze the biomechanical interactions in alveolar bone surrounding dental implants with smaller-diameter abutments. Twenty models were created that varied the implant position relative to the bone crest, loading direction, and cortical bone thickness. The results showed that loading direction and implant position were the main factors affecting stress distribution in the bone. Models with the implant shoulder placed 1 mm above the bone crest had higher stress values than other positions. Off-axis loading also significantly increased stress values compared to axial loading. The study suggests that implant position and loading direction are crucial for stress distribution in bone.
This document summarizes research on osseointegration conducted by Per-Ingvar Brinemark and collaborators since 1952. Their experimental studies in animals analyzed tissue response to implanted titanium fixtures and developed techniques for reconstructing bone defects using grafts stabilized by integrated fixtures. This led to applying osseointegration clinically in 1965 to anchor dental prostheses via titanium implants integrated directly into jawbones, providing stable long-term function without intermediate soft tissues. Their research established osseointegration as a viable method for reconstructing edentulous jaws and anchoring prostheses.
The document summarizes a study that investigated the structural and mechanical properties of human jaw bone attached to a tooth. Specifically, it examined "bundle bone", a type of adapted bone found in the jaw. Nanoscale imaging revealed bundle bone has a higher concentration of minerals and a higher elastic modulus than normal jaw bone. This suggests the adaptations in bundle bone allow it to better withstand forces from tooth movement and maintain the function of the bone-tooth complex joint. Understanding these adaptations could help address clinical issues like malocclusion and periodontal disease.
In this study, Static structural analysis of a molar tooth was performed by using FEM. The commercial finite element package ANSYS version 14.5 was used for the solution of the problem. The molars or molar teeth are large, flat teeth at the back of the mouth. They are more developed in mammals. They are used primarily to grind food during chewing. Sometimes we are using artificial teeth instead of human molar tooth during broken. Here we optimize the molar teeth using different materials like acrylic, porcelain, silver and zirconia. Taking into consideration of forces acting on the top of the first molar teeth, the deformation, strain and stress are tabulated. And here we are studying about the molar teeth.
This document discusses biomaterials with both antimicrobial and osteoinductive properties that can be applied to spinal surgery. It summarizes various biomaterials and drugs that have these properties, including nanosilver, quaternized chitosan, copper ions, and bone morphogenetic proteins (BMPs). It also discusses different methods for delivering both antimicrobial and osteoinductive drugs from biomaterials, including surface adsorption, co-encapsulation, and surface coatings. The goal is to develop materials that can simultaneously deliver these drugs to repair infected bone defects.
The documents discuss various factors that influence bone regeneration, including osteogenic cells, osteoconductive scaffolds, growth factors, and the mechanical environment. Optimal bone regeneration requires an environment that supports osteoprogenitor cell recruitment, proliferation and differentiation, angiogenesis, and extracellular matrix formation. A variety of graft materials and their properties are reviewed in relation to supporting bone healing and regeneration.
This document discusses guided tissue regeneration (GTR) for treating endodontic-periodontal lesions. It describes that GTR involves placing a barrier membrane to prevent non-bone cells from migrating first to the root surface. The success rate of treating these lesions without GTR is only 27-37%, but increases to 95% with GTR. A case example is provided of a patient with a deep periodontal pocket and bone loss treated with root canal therapy, scaling and root planing, and later GTR using an autogenous bone graft and membrane. Radiographs alone are not reliable for assessing bone fill after surgery.
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
This study used finite element analysis to analyze the biomechanical interactions in alveolar bone surrounding dental implants with smaller-diameter abutments. Twenty models were created that varied the implant position relative to the bone crest, loading direction, and cortical bone thickness. The results showed that loading direction and implant position were the main factors affecting stress distribution in the bone. Models with the implant shoulder placed 1 mm above the bone crest had higher stress values than other positions. Off-axis loading also significantly increased stress values compared to axial loading. The study suggests that implant position and loading direction are crucial for stress distribution in bone.
Comparative evaluation of natural and artificial scaffolds inRana Rana
This document summarizes a study on regenerative endodontic procedures using different scaffold materials. It provides background on regenerative endodontics and recommendations. The study compared the outcomes of using blood clots, platelet-rich fibrin (PRF), collagen, and poly-lactic-co-glycolic acid (PLGA) polymer as scaffolds in 16 immature teeth with necrotic pulps. Results found that PRF and collagen scaffolds showed better periapical healing, apical closure, root lengthening and dentin wall thickening compared to blood clots and PLGA. The conclusion is that PRF and collagen are better scaffolds than blood clots or PLGA for regenerative procedures in immature necro
1) Understanding the mechanisms of peri-implant bone healing is important as dental implants are increasingly used in more challenging situations.
2) There are differences in how cortical and trabecular bone heal, with trabecular bone healing more rapidly through new bone formation versus cortical bone healing through slower remodeling.
3) Classifying bone as "poor quality" based on its trabecular nature is a misnomer, as trabecular bone is well suited for rapid healing due to its vascular and cellular composition.
Development of bone
Microstructure of bone
Composition of bone
Formation of osteoblasts
Mineralisation of bone
Formation of osteoclasts
Resorption of bone
Macrostructure of bone
Volume changes in bone
Bone healing
1. The document reviews the use of teeth as bone graft material, noting that teeth contain minerals like hydroxyapatite that are similar to bone and promote bone remodeling.
2. Teeth contain proteins like BMP and collagen that promote bone formation. Demineralized dentin matrix from teeth has been shown to be osteoinductive and can serve as a scaffold for growth factors.
3. Studies have demonstrated the biocompatibility and osteoconductivity of particulate dentin grafts in applications like sinus lifts and socket preservation. Autogenous tooth grafts incorporate well without immune rejection.
This research article analyzes the biomechanical behavior of a virtual model of the mandibular bone loaded with monophasic and biphasic dental implants through finite element analysis (FEA). The purpose is to evaluate the biomechanical differences between monophasic and biphasic implants and assess their proper clinical use. The FEA shows that the stress distribution on the bone crest is different for the monophasic and biphasic implant configurations. Specifically, the case with the monophasic implants shows a maximum stress slightly higher than the biphasic implant case. However, the stress distribution on the mandibular ridge appears more uniform for the monophasic implant case.
Simultaneous vertical guided bone regeneration and guided tissue regeneration...threea3a
This clinical case report describes using recombinant human platelet-derived growth factor (rhPDGF-BB) along with autogenous bone and barrier membranes to reconstruct severe alveolar bone defects in the posterior maxilla through simultaneous vertical ridge augmentation and sinus floor elevation. Over 9 months of healing, complete vertical bone regeneration and new attachment to a previously denuded root surface were observed. Three implants were successfully placed and a fixed restoration was provided, demonstrating the potential for rhPDGF-BB to enhance regeneration when combined with standard bone grafting techniques and membranes. However, further controlled studies are needed to fully evaluate the benefits of using rhPDGF-BB for complex reconstruction procedures.
Clinical applications of biodentine in pediatric dentistryDR KARUNA SHARMA
This document reviews the clinical applications of Biodentine in pediatric dentistry. It summarizes that Biodentine is a new calcium-silicate based dental cement that sets faster than MTA with high biocompatibility and strength. Studies show it induces cell differentiation and biomineralization. Biodentine has various clinical applications in pediatric dentistry such as pulp capping, pulpotomies, and restorations with many studies supporting its bioactivity and clinical success.
this gives a detailed description for the bone density consideration during implant placement.
The presentation is available upon request. Mail me at apurvathampi@gmail.com
A simple method for reconstruction of severely damaged primary anterior teethDR KARUNA SHARMA
The document discusses dental caries in primary teeth, also known as early childhood caries. It notes that extraction was traditionally used to treat severely decayed primary anterior teeth but results in issues. Alternative restorative treatments discussed include direct and indirect techniques using prefabricated crowns, biologic restorations, fiber or metal posts, and composite resins. It also introduces a "reverse metal post insertion technique" using a prefabricated metal post and composite resin to restore a severely decayed primary canine.
SIMONA CAVALU_Alternative approaches using animal model for implant biomaterialsSimona Cavalu
This document summarizes an animal study testing new dental and orthopedic implant materials. It discusses the motivation for animal testing prior to human clinical trials. It describes the materials to be tested - dense alumina-zirconia composites. Small animal models (Wistar rats) and larger animal models (rabbits) are proposed. The surgical procedures, monitoring, and analysis methods are outlined, including radiography, histology, and SEM/EDX to examine the bone-implant interface. Preliminary conclusions suggest the materials show good biocompatibility in animals and that surface coatings could improve biological response. The study involves collaboration between universities in Romania and Turkey.
This curriculum vitae summarizes the professional experience and qualifications of Chi-Yuan Hong. It lists his present positions as Professor at the School of Veterinary Medicine and School of Dentistry at National Taiwan University. It then provides details of his education, certifications, teaching experience, research experience, and publications. The CV provides a comprehensive overview of Dr. Hong's academic and professional background and accomplishments.
Bone is a dynamic and highly vascularized tissue that continues to remodel throughout the lifetime.
It plays an integral role in locomotion, load-bearing capacity, and acts as a protective casing for the internal organs of the body.
Current challenges include the engineering of materials that can match both the mechanical and biological context of real bone tissue matrix and support the vascularization of large tissue constructs.
Scaffolds with new levels of biofunctionality that attempt to recreate nanoscale topographical and biofactor cues from the extracellular environment are emerging as interesting candidate biomimetic materials.
Innovative Potential of Periodontal Ligament Cell Sheet Engineering in Functi...CrimsonpublishersITERM
Innovative Potential of Periodontal Ligament Cell Sheet Engineering in Functional Implant Therapy by Isao Ishikawa in Innovation in Tissue Engineering & Regenerative Medicine
Alveolar bone forms in conjunction with tooth development to support teeth and give attachment to muscles. It is composed mainly of hydroxyapatite and collagen and contains osteoblasts, osteocytes, and osteoclasts. The alveolar bone undergoes remodeling through the balanced actions of osteoblasts, which form new bone, and osteoclasts, which resorb old bone. This allows the alveolar bone to maintain its shape and position relative to the teeth. Interruptions in the bone like fenestrations and dehiscences can complicate dental procedures or lead to issues like gingival recession.
This document provides a summary of a case report from Periodontics of the Desert regarding the benefits of flap access in treating periodontal disease. Flap access allows for direct visualization of the root surface and access for calculus removal. It summarizes that flap access permits thorough debridement and smoothing of root surfaces, eliminating periodontal pockets and regenerating lost bone and soft tissue for improved periodontal health.
This document provides an overview of regenerative endodontics, which aims to regenerate dental tissues through biologically-based procedures using stem cells, growth factors, and scaffolds. Key elements for pulp regeneration include reliable stem cell sources, such as dental pulp stem cells, growth factors to stimulate cell proliferation and differentiation, and appropriate scaffolds. Potential regenerative therapies include revascularization, stem cell therapy, scaffold implantation, and gene delivery. Measuring clinical outcomes and further applications are areas of future focus to develop regenerative endodontic therapies.
Different clinical applications of bondable reinforcement ribbond in Pediatri...DR KARUNA SHARMA
The document discusses the use of fiber-reinforced composite (FRC) materials in dentistry, specifically focusing on Ribbond fibers. It describes different types of fibers that have been used such as glass, carbon, Kevlar, and polyethylene fibers. Ribbond fibers are discussed in depth, noting their properties like high strength, flexibility, biocompatibility and esthetics. The document then presents four clinical case studies where Ribbond fibers were used for different applications: 1) as a fixed space maintainer, 2) to create a fiber-reinforced composite fixed partial denture with a natural tooth pontic, 3) as an endodontic post and core, and 4) to splint traumatized teeth
This study used 3D finite element analysis to investigate the effect of different bone qualities (D1-D4) on stress distribution in an implant-supported mandibular crown. The analysis found that bone qualities D3 and D4 experienced the highest von Mises stresses at the neck of the implant under a 300N load. Placement of implants in bone with greater cortical thickness and density (D1-D2) reduced stress concentration and is more favorable for implant stabilization and osseointegration. However, long-term clinical trials are needed to determine the relationship between bone quality and stress distribution on implant success.
This document discusses regenerative endodontics and the potential for dental pulp stem cells to regenerate damaged dentin and pulp tissues. It describes how dental pulp stem cells can proliferate and differentiate into odontoblasts and other cell types, potentially regenerating the dentin-pulp complex. Studies with dental pulp stem cells in scaffolds and with growth factors have shown new dentin formation in animal models, raising the possibility of clinical treatments to repair teeth and prevent tooth loss. The document reviews the key components needed for regenerative endodontics, including appropriate stem cells, scaffolds, and growth factors.
A detailed description of regenerative endodontics with illustrated journals right from its history,, needs, till its future advancements and challenges...
Comparative evaluation of natural and artificial scaffolds inRana Rana
This document summarizes a study on regenerative endodontic procedures using different scaffold materials. It provides background on regenerative endodontics and recommendations. The study compared the outcomes of using blood clots, platelet-rich fibrin (PRF), collagen, and poly-lactic-co-glycolic acid (PLGA) polymer as scaffolds in 16 immature teeth with necrotic pulps. Results found that PRF and collagen scaffolds showed better periapical healing, apical closure, root lengthening and dentin wall thickening compared to blood clots and PLGA. The conclusion is that PRF and collagen are better scaffolds than blood clots or PLGA for regenerative procedures in immature necro
1) Understanding the mechanisms of peri-implant bone healing is important as dental implants are increasingly used in more challenging situations.
2) There are differences in how cortical and trabecular bone heal, with trabecular bone healing more rapidly through new bone formation versus cortical bone healing through slower remodeling.
3) Classifying bone as "poor quality" based on its trabecular nature is a misnomer, as trabecular bone is well suited for rapid healing due to its vascular and cellular composition.
Development of bone
Microstructure of bone
Composition of bone
Formation of osteoblasts
Mineralisation of bone
Formation of osteoclasts
Resorption of bone
Macrostructure of bone
Volume changes in bone
Bone healing
1. The document reviews the use of teeth as bone graft material, noting that teeth contain minerals like hydroxyapatite that are similar to bone and promote bone remodeling.
2. Teeth contain proteins like BMP and collagen that promote bone formation. Demineralized dentin matrix from teeth has been shown to be osteoinductive and can serve as a scaffold for growth factors.
3. Studies have demonstrated the biocompatibility and osteoconductivity of particulate dentin grafts in applications like sinus lifts and socket preservation. Autogenous tooth grafts incorporate well without immune rejection.
This research article analyzes the biomechanical behavior of a virtual model of the mandibular bone loaded with monophasic and biphasic dental implants through finite element analysis (FEA). The purpose is to evaluate the biomechanical differences between monophasic and biphasic implants and assess their proper clinical use. The FEA shows that the stress distribution on the bone crest is different for the monophasic and biphasic implant configurations. Specifically, the case with the monophasic implants shows a maximum stress slightly higher than the biphasic implant case. However, the stress distribution on the mandibular ridge appears more uniform for the monophasic implant case.
Simultaneous vertical guided bone regeneration and guided tissue regeneration...threea3a
This clinical case report describes using recombinant human platelet-derived growth factor (rhPDGF-BB) along with autogenous bone and barrier membranes to reconstruct severe alveolar bone defects in the posterior maxilla through simultaneous vertical ridge augmentation and sinus floor elevation. Over 9 months of healing, complete vertical bone regeneration and new attachment to a previously denuded root surface were observed. Three implants were successfully placed and a fixed restoration was provided, demonstrating the potential for rhPDGF-BB to enhance regeneration when combined with standard bone grafting techniques and membranes. However, further controlled studies are needed to fully evaluate the benefits of using rhPDGF-BB for complex reconstruction procedures.
Clinical applications of biodentine in pediatric dentistryDR KARUNA SHARMA
This document reviews the clinical applications of Biodentine in pediatric dentistry. It summarizes that Biodentine is a new calcium-silicate based dental cement that sets faster than MTA with high biocompatibility and strength. Studies show it induces cell differentiation and biomineralization. Biodentine has various clinical applications in pediatric dentistry such as pulp capping, pulpotomies, and restorations with many studies supporting its bioactivity and clinical success.
this gives a detailed description for the bone density consideration during implant placement.
The presentation is available upon request. Mail me at apurvathampi@gmail.com
A simple method for reconstruction of severely damaged primary anterior teethDR KARUNA SHARMA
The document discusses dental caries in primary teeth, also known as early childhood caries. It notes that extraction was traditionally used to treat severely decayed primary anterior teeth but results in issues. Alternative restorative treatments discussed include direct and indirect techniques using prefabricated crowns, biologic restorations, fiber or metal posts, and composite resins. It also introduces a "reverse metal post insertion technique" using a prefabricated metal post and composite resin to restore a severely decayed primary canine.
SIMONA CAVALU_Alternative approaches using animal model for implant biomaterialsSimona Cavalu
This document summarizes an animal study testing new dental and orthopedic implant materials. It discusses the motivation for animal testing prior to human clinical trials. It describes the materials to be tested - dense alumina-zirconia composites. Small animal models (Wistar rats) and larger animal models (rabbits) are proposed. The surgical procedures, monitoring, and analysis methods are outlined, including radiography, histology, and SEM/EDX to examine the bone-implant interface. Preliminary conclusions suggest the materials show good biocompatibility in animals and that surface coatings could improve biological response. The study involves collaboration between universities in Romania and Turkey.
This curriculum vitae summarizes the professional experience and qualifications of Chi-Yuan Hong. It lists his present positions as Professor at the School of Veterinary Medicine and School of Dentistry at National Taiwan University. It then provides details of his education, certifications, teaching experience, research experience, and publications. The CV provides a comprehensive overview of Dr. Hong's academic and professional background and accomplishments.
Bone is a dynamic and highly vascularized tissue that continues to remodel throughout the lifetime.
It plays an integral role in locomotion, load-bearing capacity, and acts as a protective casing for the internal organs of the body.
Current challenges include the engineering of materials that can match both the mechanical and biological context of real bone tissue matrix and support the vascularization of large tissue constructs.
Scaffolds with new levels of biofunctionality that attempt to recreate nanoscale topographical and biofactor cues from the extracellular environment are emerging as interesting candidate biomimetic materials.
Innovative Potential of Periodontal Ligament Cell Sheet Engineering in Functi...CrimsonpublishersITERM
Innovative Potential of Periodontal Ligament Cell Sheet Engineering in Functional Implant Therapy by Isao Ishikawa in Innovation in Tissue Engineering & Regenerative Medicine
Alveolar bone forms in conjunction with tooth development to support teeth and give attachment to muscles. It is composed mainly of hydroxyapatite and collagen and contains osteoblasts, osteocytes, and osteoclasts. The alveolar bone undergoes remodeling through the balanced actions of osteoblasts, which form new bone, and osteoclasts, which resorb old bone. This allows the alveolar bone to maintain its shape and position relative to the teeth. Interruptions in the bone like fenestrations and dehiscences can complicate dental procedures or lead to issues like gingival recession.
This document provides a summary of a case report from Periodontics of the Desert regarding the benefits of flap access in treating periodontal disease. Flap access allows for direct visualization of the root surface and access for calculus removal. It summarizes that flap access permits thorough debridement and smoothing of root surfaces, eliminating periodontal pockets and regenerating lost bone and soft tissue for improved periodontal health.
This document provides an overview of regenerative endodontics, which aims to regenerate dental tissues through biologically-based procedures using stem cells, growth factors, and scaffolds. Key elements for pulp regeneration include reliable stem cell sources, such as dental pulp stem cells, growth factors to stimulate cell proliferation and differentiation, and appropriate scaffolds. Potential regenerative therapies include revascularization, stem cell therapy, scaffold implantation, and gene delivery. Measuring clinical outcomes and further applications are areas of future focus to develop regenerative endodontic therapies.
Different clinical applications of bondable reinforcement ribbond in Pediatri...DR KARUNA SHARMA
The document discusses the use of fiber-reinforced composite (FRC) materials in dentistry, specifically focusing on Ribbond fibers. It describes different types of fibers that have been used such as glass, carbon, Kevlar, and polyethylene fibers. Ribbond fibers are discussed in depth, noting their properties like high strength, flexibility, biocompatibility and esthetics. The document then presents four clinical case studies where Ribbond fibers were used for different applications: 1) as a fixed space maintainer, 2) to create a fiber-reinforced composite fixed partial denture with a natural tooth pontic, 3) as an endodontic post and core, and 4) to splint traumatized teeth
This study used 3D finite element analysis to investigate the effect of different bone qualities (D1-D4) on stress distribution in an implant-supported mandibular crown. The analysis found that bone qualities D3 and D4 experienced the highest von Mises stresses at the neck of the implant under a 300N load. Placement of implants in bone with greater cortical thickness and density (D1-D2) reduced stress concentration and is more favorable for implant stabilization and osseointegration. However, long-term clinical trials are needed to determine the relationship between bone quality and stress distribution on implant success.
This document discusses regenerative endodontics and the potential for dental pulp stem cells to regenerate damaged dentin and pulp tissues. It describes how dental pulp stem cells can proliferate and differentiate into odontoblasts and other cell types, potentially regenerating the dentin-pulp complex. Studies with dental pulp stem cells in scaffolds and with growth factors have shown new dentin formation in animal models, raising the possibility of clinical treatments to repair teeth and prevent tooth loss. The document reviews the key components needed for regenerative endodontics, including appropriate stem cells, scaffolds, and growth factors.
A detailed description of regenerative endodontics with illustrated journals right from its history,, needs, till its future advancements and challenges...
Cellular, Molecular, and Genetic Determinants OF Tooth Eruption /prosthodonti...Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Tooth bioengineering and the next generation of dentistryAmir Rajaey
Tooth bioengineering and the next generation of dentistry.
As a result of numerous rapid and exciting developments in tissue engineering technology, scientists are able to regenerate a fully functional tooth in animal models, from a bioengineered tooth germ. Advances in technology, together with our understanding of the mechanisms of tooth development and studies dealing with dentally derived stem cells, have led to significant progress in the field of tooth regeneration
This document provides an introduction to regenerative endodontics, which aims to replace damaged dental structures through biological procedures rather than traditional root canal treatments. It defines key concepts like regeneration versus repair and discusses the history and components of regenerative endodontics. Specifically, it outlines sources of stem cells in the dental pulp, papilla, and periapical tissues that can be recruited to sites of injury and differentiated to produce new tissues. Growth factors and scaffolds provide signaling and structure to guide the stem cells in regeneration. The ultimate goals are to eliminate symptoms, enhance bone healing, and potentially increase root length, though complete regeneration of the original pulp-dentine complex is difficult to achieve.
Stem cells found in dental tissues such as dental pulp, dental pulp of deciduous teeth, apical papilla, and dental follicle can differentiate into odontoblast cells and have potential applications in dental tissue regeneration and repair. There are several types of dental stem cells that can potentially be used to regenerate dental tissues and whole teeth. Delivery of growth factors has shown potential to induce homing of endogenous stem cells to regenerate dental pulp-like tissue in root canals of extracted human teeth implanted in mice without cell transplantation. Further research is still needed but dental stem cells show promise for applications in dental tissue engineering and whole tooth regeneration.
This document discusses prospects for tooth regeneration. It begins by reviewing tooth development as a model for regeneration, noting the stages of bud, cap, bell, crown and root. It then discusses the regenerative capabilities of naturally formed dental tissues, noting that enamel has no regenerative ability while dentin, cementum, pulp, and alveolar bone do to varying degrees. The document concludes by discussing postnatal dental stem cells that have been identified and their role in dental tissue regeneration experiments that have generated tooth crowns containing enamel, dentin, pulp and bone.
This document provides information on various materials used for obturation in primary teeth pulpectomy procedures. It discusses the properties, advantages and disadvantages of commonly used materials like zinc oxide eugenol, iodoform-based pastes (Walcoff paste, KRI paste, Maisto paste), Vitapex, and calcium hydroxide mixtures. It summarizes studies comparing the success rates, resorption rates, and antibacterial effects of these materials. The goal of obturation is to disinfect the root canal system and create an effective seal, while using a material that will resorb at a rate similar to root resorption in primary teeth. No single material meets all ideal criteria.
The document discusses clinical considerations in tooth development. It outlines four key signaling pathways - BMP, FGF, SHH, and Wnt - that are critical for proper tooth development. Disruption of these pathways can lead to developmental defects of enamel, dentin, and cementum. The document also reviews genetic and molecular factors involved in stages of tooth development including bud formation, crown patterning, root formation, and mineralization.
Osseo-integrated dental implants have been widely used for the rehabilitation of tooth loss. Although dental implants
are considered an available treatment in the paradigm shift from traditional dental therapies, such as fixed dental bridges and
removable dentures, the fundamental problems must be overcome prior to their clinical use in young patients who are still
undergoing jawbone growth. A bio-engineered functional bio-hybrid implant that is combined with adult-derived periodontal
tissue and attached with bone tissue can act as a substitute for cementum. This bio-hybrid implant was successfully engrafted
and it restored physiological function, including bone remodelling, regeneration and appropriate responsiveness to noxious
stimuli. Thus, this article reviews the functional bio-hybrid implant’s potential for clinical use as a next-generation dental
implant using adult-derived tissues.
This document discusses advances in stem cell therapy using dental stem cells. It summarizes that dental stem cells, such as dental pulp stem cells and stem cells from exfoliated deciduous teeth, have been shown to be a better source of mesenchymal stem cells than bone marrow. These dental stem cells can be isolated from accessible dental tissues, have high proliferative ability, and can differentiate into various cell types. Cryopreserved dental pulp tissues from exfoliated deciduous teeth are a feasible source of stem cells that maintain stem cell properties and have shown therapeutic potential for regenerative medicine applications and treating conditions like immune disorders.
This document provides an overview of regenerative endodontics, which aims to regenerate dental tissues through biological procedures. The key elements required are stem cells, growth factors, and scaffolds. Stem cells that may be suitable include dental pulp stem cells, stem cells from exfoliated deciduous teeth, and stem cells of the apical papilla. Regenerative endodontic procedures seek to regenerate pulp-like tissues and stimulate further root development, offering improved outcomes over current treatments. Additional research is needed to develop these techniques for clinical use in regenerating damaged dental tissues.
This document discusses regenerative bone substitutes produced by Tecnoss called OsteoBiol. It summarizes that OsteoBiol is made of a dual-phase matrix containing both mineral and collagen phases that is highly similar to natural bone. This collagen content allows it to integrate well with the body and be gradually replaced by new bone formation over time. The document highlights several studies demonstrating OsteoBiol's osteoconductive properties, biocompatibility, and ability to promote osteoblast activity and new bone growth. It positions OsteoBiol as a versatile product line for various bone regeneration procedures and clinical indications.
Regenerative endodontic procedures are designed to replace damaged structures, including dentin and root structures, as well as cells of the pulp-dentin complex
Dr. Jamal Giri presented on the development of dentition and tooth eruption. The presentation covered the stages of tooth development from the bud stage through root formation and eruption. It discussed the various theories of tooth eruption including the roles of root formation, bone remodeling, the periodontal ligament, hydrostatic pressure, and the dental follicle. It also summarized Proffit's contributions regarding the mechanism and control of tooth eruption, including maintaining an eruptive force and clearing the eruption path.
This document discusses revascularization/regeneration procedures performed on immature molars. It defines regenerative endodontics as biologically based procedures to replace damaged pulp and root structures. The objectives of regenerative endodontics are to regenerate pulp-like tissue, dentin, and root structures. Stem cells, scaffolds, and growth factors are key elements in dental tissue engineering and regeneration procedures. The document also discusses the use of triantibiotic pastes containing ciprofloxacin, metronidazole, and minocycline to disinfect immature teeth and enable revascularization.
This document provides an introduction to regenerative endodontics and minimally invasive endodontics. It discusses the goals of regenerative endodontics, which include eliminating symptoms, promoting bone healing, and increasing root length. Regenerative endodontics aims to replace damaged pulp and root structures using stem cells. The document reviews the history and terminology of regenerative endodontics. It also examines the tissue outcomes of regenerative procedures, discussing that repair rather than regeneration often occurs. The principles of regeneration and repair in endodontics are explored, as well as pulp biology and the use of bioactive materials to promote healing.
Regenerative endodontics aims to regenerate damaged pulp and root structures through biologically-based procedures. Historically, studies in the 1960s-70s showed blood clots could induce tissue formation in root canals. Current methods include placing stem cells on scaffolds with growth factors in the root canal to regenerate the pulp-dentin complex. Triple antibiotic paste, calcium hydroxide, and MTA are used as antimicrobial medicaments. The protocol involves inducing bleeding into the root canal to form a blood clot which triggers regeneration. The goal is periradicular health and evidence of vital regenerated tissue through radiographic and clinical measures.
STEM CELLS IN HUMAN EXFOLIATED DECIDUOUS TEETH(SHED)Upama Sishan
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Anatomically shaped tooth and periodontal regeneration by cell homing
1. JDR OnlineFirst, published on May 6, 2010 as doi:10.1177/0022034510370803
RAPID COMMUNICATION
Biomaterials & Bioengineering
K. Kim+, C.H. Lee+, B.K. Kim,
and J.J. Mao*
Anatomically shaped Tooth
Columbia University College of Dental Medicine, 630 W.
and Periodontal Regeneration
168th St., PH7E – CDM, New York, NY 10032, USA;
+
authors contributing equally to the technical aspects of this by Cell Homing
project; *corresponding author, jmao@columbia.edu
J Dent Res X(X):xx-xx, XXXX
ABsTRACT INTRODUCTION
Tooth regeneration by cell delivery encounters
translational hurdles. We hypothesized that ana-
tomically correct teeth can regenerate in scaffolds
A tooth is a major organ consisting of biological viable pulp encased in
mineralized dentin that may be covered with cementum and enamel
ontogenetically in various species (Poole, 1967). Life ends in wildlife spe-
without cell transplantation. Novel, anatomically
cies after complete tooth loss. In humans, tooth loss can lead to physical and
shaped human molar scaffolds and rat incisor scaf-
mental suffering that compromises self-esteem and quality of life (Pihlstrom
folds were fabricated by 3D bioprinting from a
et al., 2005; USDHHS, 2005). Contemporary dentistry restores missing teeth
hybrid of poly-ε-caprolactone and hydroxyapatite
with dental implants or dentures. Dental implants, despite being the preferred
with 200-µm-diameter interconnecting microchan-
treatment modality, can fail and have no ability to remodel with surrounding
nels. In each of 22 rats, an incisor scaffold was
bone, which undergoes physiologically necessary remodeling throughout life
implanted orthotopically following mandibular
(Ferreira et al., 2007). Accordingly, there has been intensifying interest in the
incisor extraction, whereas a human molar scaf-
regeneration of orofacial tissues, including teeth (Modino and Sharpe, 2005;
fold was implanted ectopically into the dorsum.
Young et al., 2005; Mao et al., 2006).
Stromal-derived factor-1 (SDF1) and bone mor-
Cell delivery has been the predominant approach in tooth regeneration.
phogenetic protein-7 (BMP7) were delivered in
Disassociated cells of porcine or rat tooth buds in biomaterials yielded puta-
scaffold microchannels. After 9 weeks, a putative
tive dentin and enamel organ (Young et al., 2002; Duailibi et al., 2004). Tooth
periodontal ligament and new bone regenerated at
bud cells and bone marrow osteoprogenitor cells in collagen, PLGA, or silk-
the interface of rat incisor scaffold with native
protein scaffolds induced putative tooth-like tissues, alveolar bone, and
alveolar bone. SDF1 and BMP7 delivery not only
periodontal ligament (Young et al., 2005; Duailibi et al., 2008; Kuo et al.,
recruited significantly more endogenous cells, but
2008). Embryonic oral epithelium and adult mesenchyme together up-regu-
also elaborated greater angiogenesis than growth-
late odontogenesis genes upon mutual induction, and yielded dental structures
factor-free control scaffolds. Regeneration of
upon transplantation into adult renal capsules or jaw bone (Ohazama et al.,
tooth-like structures and periodontal integration by
2004). Similarly, implantation of E14.5 rat molar rudiments into adult mouse
cell homing provide an alternative to cell delivery,
maxilla produced tooth-like structures with surrounding bone (Modino and
and may accelerate clinical applications.
Sharpe, 2005; Mantesso and Sharpe, 2009). Multipotent cells of the tooth api-
cal papilla in tricalcium phosphate in swine incisor extraction sockets gener-
KEY WORDs: tooth regeneration, cell homing, ated soft and mineralized tissues resembling the periodontal ligament
stem cells, bioprinting, periodontal. (Sonoyama et al., 2006). Mouse E14.5 oral epithelium and dental mesen-
chyme were reconstituted in collagen gel and cultured ex vivo (Nakao et al.,
2007), and, when they were implanted into the maxillary molar extraction
sockets in 5-week-old mice, tooth morphogenesis took place and was fol-
lowed by eruption into occlusion (Ikeda et al., 2009). Several studies have
begun to tackle an obligatory task of scale-up toward human tooth size (Xu
et al., 2008; Abukawa et al., 2009).
Tooth regeneration by cell transplantation is a meritorious approach.
However, there are hurdles in the translation of cell-delivery-based tooth
regeneration into therapeutics. Autologous embryonic tooth germ cells are
inaccessible for human applications (Modino and Sharpe, 2005; Nakao et al.,
2007; Ikeda et al., 2009). Xenogenic embryonic tooth germ cells (from non-
human species) may elicit immunorejection and tooth dysmorphogenesis.
DOI: 10.1177/0022034510370803
Autologous post-natal tooth germ cells (e.g., third molars) or autologous den-
tal pulp stem cells are of limited availability. Regardless of the cell source,
Received November 3, 2009; Last revision March 23, 2010; cell delivery for tooth regeneration, similar to cell-based therapies for
Accepted March 26, 2010 other tissues, encounters translational barriers (Ahsan et al., 2007; Evaluation
1
2. 2 Kim et al. J Dent Res X(X) XXXX
cell-homing approach for tooth regeneration. A novel anatomically
shaped scaffold was fabricated with interconnecting microchan-
nels (diam., 200 µm) as conduits for the homing of host endog-
enous cells and angiogenesis. Remarkably, a putative periodontal
ligament and de novo alveolar bone regenerated at the scaffold’s
interface with native alveolar bone upon 9-week in vivo implan-
tation. Cell homing by stromal-derived factor-1 (SDF1) and
bone morphogenetic protein-7 (BMP7) not only recruited
endogenous cells, but also induced angiogenesis. These findings
represent the first demonstration of de novo formation of ana-
tomically shaped tooth-like structures and periodontal integra-
tion in vivo, and may provide a clinically translatable approach.
MATERIAls & METHODs
Design and 3D Bioprinting of Anatomically
shaped Tooth scaffolds
Anatomic shape and dimensions of the rat mandibular central
incisor were derived from multiple slices of 2D laser scanning
of extracted rat incisor per our prior methods (Lee et al., 2009;
Stosich et al., 2009). The dimensions of the permanent man-
dibular first molar were derived from textbook averages and
therefore were exempt from institutional review board approval.
Scaffolds with the shape of the rat mandibular central incisor
(Fig. 1A) and human mandibular first molar (Fig. 1B) were
fabricated via 3D layer-by-layer apposition (Lee et al., 2009;
Stosich et al., 2009). The composite consisted of 80 wt% poly-
caprolactone (PCL) and 20 wt% of hydroxyapatite (HA) (Sigma,
St. Louis, MO, USA). PCL-HA was co-molten at 120°C and
dispensed through a 27-gauge metal nozzle to create repeating
3D microstrands (200-µm wall thickness) and interconnecting
microchannels (diam., 200 µm) (Figs. 1C, 1D).
Delivery of Bioactive Cues in Microchannels
All scaffolds were sterilized in ethylene oxide for 24 hrs. A
blended cocktail of SDF1 (100 ng/mL) and BMP7 (100 ng/mL)
was adsorbed in 2 mg/mL neutralized type I collagen solution
(all from R&D, Minneapolis, MN, USA). SDF1 was selected for
its effects to bind to CXCR4 receptors of multiple cell lineages,
including mesenchymal stem/progenitor cells (Belema-Bedada
Figure 1. Design and fabrication of anatomically shaped human and et al., 2008; Kitaori et al., 2009). BMP7 was selected for its
rat tooth scaffolds by 3D bioprinting. Anatomic shape of the rat effects on dental pulp cells, fibroblasts, and osteoblasts in elabo-
mandibular central incisor (A) and human mandibular first molar (B) rating mineralization (Goldberg et al., 2001; Rutherford, 2001).
were used for 3D reconstruction and bioprinting of a hybrid scaffold SDF1 and BMP7 doses were chosen from in vivo work (Vaccaro
of poly-ε-caprolactone and hydroxyapatite, with 200-µm microstrands
et al., 2008; Kitaori et al., 2009). SDF1- and BMP7-loaded col-
and interconnecting microchannels (diam., 200 µm), which serve as
conduits for cell homing and angiogenesis (C,D). A blended cocktail of
lagen solution was infused in scaffold microchannels by micro-
stromal-derived factor-1 (100 ng/mL) and bone morphogenetic pipettes (N = 11 for rat incisor scaffolds; N = 11 for human
protein-7 (100 ng/mL) was delivered in 2 mg/mL neutralized type I molar scaffolds) (Figs. 1E, 1F), and crosslinked at 37°C for 1 hr.
collagen solution and infused in scaffold microchannels for rat incisor Control scaffolds were infused with the same collagen gel, but
scaffold (E) and human molar scaffold (F), followed by gelation. without growth-factor delivery (N = 11 for rat incisor scaffolds;
N = 11 for human molar scaffolds).
criteria for musculoskeletal and craniofacial tissue engineering
constructs, 2008). To date, excessive cost of commercialization
In vivo Tooth Regeneration Models
and difficulties in regulatory approval have precluded any sig-
nificant clinical translation of tooth regeneration. As a first step Following IACUC approval, 22 male (12-week-old) Sprague-
to addressing the limitations of cell delivery, we devised a Dawley rats were randomly divided equally into treatment and
3. J Dent Res X(X) XXXX Tooth and Periodontal Regeneration by Cell Homing 3
control groups (Charles River, NY,
USA). All rats were anesthetized by
i.p. administration of ketamine (80
mg/kg) and xylazine (5 mg/kg). A
2-cm incision was made in the dor-
sum. Human mandibular molar
scaffolds were implanted into surgi-
cally created subcutaneous pouches
(Fig. 2A), followed by wound clo-
sure. The rat right mandibular cen-
tral incisor was then extracted with
periotome (Figs. 2C, 2D), followed
by implantation of the anatomically
shaped mandibular incisor scaffold
(Fig. 2E) into the extraction socket.
The tooth was carefully luxated
with the smallest possible perio-
tome and Allen’s microsurgical
instruments, to minimize root frac-
tures. Practice was needed to mini-
mize root fracture when extracting
rat lower incisors. Upon the com-
pletion of pilot experiments, we
were able to perform atraumatic Figure 2. In vivo orthotopic and ectopic implantation of anatomically shaped tooth scaffolds. (A)
extractions without fracturing the In vivo implantation of human mandibular molar scaffold into rat’s dorsum constitutes an ectopic
model for tooth regeneration. (B) Harvest of human molar scaffold showing integration and tissue
root (Fig. 2D). In rare cases of root
ingrowth. (C) Extraction of the right rat mandibular central incisor. (D) The extracted rat mandibular
fracture, the animals were excluded. central incisor. (E) The fabricated rat mandibular central incisor scaffold. (F) Harvest of in vivo-
The mandibular incisor scaffold implanted rat mandibular central incisor scaffold orthotopically in the extraction socket showing
protruded 3 mm from the alveolar integration of the implanted scaffold. Scale: 5 mm.
edge. The flap was advanced for
primary closure around the scaffold. Buprenorphine (0.05 mg/kg) the rat mandibular incisor integrated with surrounding tissue,
was administered i.p. post-operatively for analgesia. showing tissue ingrowth into scaffold microchannels (Fig. 3A).
It was not possible to separate the implanted scaffolds without
sample Harvesting, Tissue Analysis, and statistics physical damage to surrounding tissue. Microscopically, the
scaffolds within the extraction sockets clearly showed multiple
Nine weeks post-surgery, all rats were killed by pentobarbital
tissue phenotypes, including the native alveolar bone (b), newly
overdose. The dorsum scaffolds were retrieved with surrounding
formed bone (nb), and a fibrous tissue interface reminiscent of
fascia (Fig. 2B). The rat incisor scaffolds were harvested with sur-
the periodontal ligament (pdl) (Fig. 3A). The newly formed
rounding bone and native tooth structures (Fig. 2F). All samples
bone (nb) showed ingrowth into microchannel openings and
were fixed in 10% formalin, embedded in poly(methyl methacry-
inter-staggered with scaffold microstrands (s) (Fig. 3A). Higher
late) (PMMA), and sectioned at 5-µm thickness for hematoxylin
magnification showed newly formed bone (nb) with bone tra-
and eosin (H&E) and von Kossa (VK) staining (HSRL, Mount
beculae-like structures (arrows in Fig. 3B) and embedded cells
Jackson, VA, USA). PMMA was used because PCL-HA scaffolds
resembling osteocytes. Immediately adjacent is a structure
cannot be de-mineralized for paraffin embedding. The average
reminiscent of the periodontal ligament consisting of fibroblast-
areal cell density and blood vessel numbers were quantified from
like cells and collagen-like structures (pdl in Fig. 3B). Von
the coronal, middle, and apical thirds of the rat incisor scaffolds
Kossa preparation showed that the newly formed bone (nb) was
(Fig. 3J) and similarly of the human molar scaffolds (Fig. 4G) by
well-mineralized, in contrast to adjacent unmineralized, putative
a blinded and calibrated examiner. Upon confirmation of normal
periodontal ligament (pdl) (Fig. 3C). Although host cells popu-
data distribution, Students’ t tests were used to compare the treated
lated the microchannels of growth-factor-free control scaffolds
and control groups, with alpha at 0.05.
(Fig. 3D), combined SDF1 and BMP7 delivery (Fig. 3E) homed
significantly more cells into the microchannels of the rat incisor
REsUlTs scaffolds (p < 0.01) (Fig. 3F). Angiogenesis took place in scaf-
folds’ microchannels with or without growth-factor delivery
Orthotopic Tooth Regeneration without
(Figs. 3G, 3H). Quantitatively, combined SDF1 and BMP7
Cell Transplantation
delivery elaborated significantly more blood vessels than the
The mandibular incisor extraction socket represents an ortho- growth-factor-free group (p < 0.05) (Fig. 3I). The numbers
topic location for tooth regeneration. Scaffolds in the shape of of recruited cells and blood vessels were quantified from 3
4. 4 Kim et al. J Dent Res X(X) XXXX
Ectopic Tooth Regeneration
without Cell Transplantation
Human mandibular molar scaffolds
implanted into the dorsum repre-
sent an ectopic location for tooth
regeneration. Microscopically, host
cells populated scaffold microchan-
nels without growth-factor delivery
(Fig. 4A). Quantitatively, combined
SDF1 and BMP7 delivery (Fig. 4B)
homed significantly more cells into
the microchannels of the human
molar scaffolds than without
growth-factor delivery (p < 0.01)
(Fig. 4C). Angiogenesis took place
in microchannels with or without
growth-factor delivery (Figs. 4A,
4B). However, combined SDF1 and
BMP7 delivery elaborated signifi-
cantly more blood vessels than
without growth-factor delivery (p <
0.05) (Fig. 4D). Mineral tissue was
present in isolated areas in micro-
channels adjacent to blood vessels
and abundant cells (Fig. 4E). Von
Kossa staining confirmed ectopic
mineralization (Fig. 4F), likely
owing to BMP7 delivery. Tissue
sections from coronal, middle, and
two root portions of human molar
scaffolds were quantified for cell
density and angiogenesis (Fig. 4G).
Figure 3. Orthotopic tooth regeneration. (A) The rat mandibular incisor scaffold integrated with
DIsCUssION
surrounding tissue, showing tissue ingrowth into scaffold microchannels and multiple tissue phenotypes, These findings represent the first
including the native alveolar bone (b), newly formed bone (nb), and a fibrous tissue interface
report of regeneration of anatomi-
reminiscent of the periodontal ligament (pdl). The newly formed bone (nb) showed ingrowth into
microchannel openings and inter-staggered with scaffold microstrands (s). (B) Newly formed bone (nb)
cally shaped tooth-like structures
has bone trabeculae-like structures (arrows) and embedded osteocyte-like cells, immediately adjacent in vivo, and by cell homing without
to a putative periodontal ligament (pdl) consisting of fibroblast-like cells and collagen buddle-like cell delivery. The potency of cell
structures. (C) Newly formed bone (nb) is well-mineralized (von Kossa preparation), in contrast to the homing is substantiated not only
adjacent unmineralized, putative periodontal ligament (pdl). (D) Cells populated the scaffold’s by cell recruitment into scaffold
microchannels even without growth-factor delivery. Remarkably, SDF1 and BMP7 delivery yielded microchannels, but also by regen-
substantial cell homing in microchannels (E). (F) Combined SDF1 and BMP7 delivery homed
eration of a putative periodontal
significantly more cells into microchannels than without growth-factor delivery (p < 0.01; N = 11).
Angiogenesis took place in scaffolds’ microchannels without growth-factor delivery (G), but was more ligament and newly formed alveo-
substantial with growth-factor delivery (H). (I) Combined SDF1 and BMP7 delivery elaborated lar bone. Tooth regeneration
significantly more blood vessels than without growth-factor delivery (p < 0.05; N = 11). (J) The requires condensation of sufficient
numbers of recruited cells and blood vessels were quantified from 3 different locations along the entire cells of multiple lineages (Modino
root length of the rat mandibular incisor scaffold: the superior region of alveolar ridge and the inferior and Sharpe, 2005; Yelick and
region of root apex, with a midpoint in between. s, scaffold; GF, growth factor(s). Scale: 100 µm. Vacanti, 2006). The observed puta-
tive periodontal ligament and
newly formed alveolar bone sug-
different locations along the entire root length of the rat man- gest the ability of SDF1 and/or BMP7 to recruit multiple cell
dibular incisor scaffold: the superior region of the alveolar lineages. SDF1 is chemotactic for bone marrow stem/progenitor
ridge, and the midpoint and the inferior region of the root apex cells and endothelial cells, both of which are critical for angio-
(Fig. 3J). genesis (Herodin et al., 2003; Belema-Bedada et al., 2008; Nait
5. J Dent Res X(X) XXXX Tooth and Periodontal Regeneration by Cell Homing 5
Lechguer et al., 2008). SDF1 binds
to CXCR4, a chemokine receptor
for endothelial cells and bone mar-
row stem/progenitor cells (Belema-
Bedada et al., 2008; Kitaori et al.,
2009). Here, SDF1 likely has homed
mesenchymal and endothelial stem/
progenitor cells in native alveolar
bone into porous tooth scaffolds that
were implanted in rat jaw bone, and
connective tissue progenitor cells in
dorsal subcutaneous tissue into
human molar scaffold (Alhadlaq
and Mao, 2004; Steinhardt et al.,
2008; Crisan et al., 2009). BMP7
plays important roles in osteoblast
differentiation and phosphorylation
via SMAD pathways, which induces
transcription of multiple osteogenic/
odontogenic genes (Hahn et al.,
1992; Itoh et al., 2001). Here, BMP7
likely is responsible for newly
Figure 4. Ectopic tooth regeneration. (A) In human mandibular molar scaffolds, cells populated
formed, mineralized alveolar bone scaffold microchannels without growth-factor delivery. (B) Combined SDF1 and BMP7 delivery
in rat extraction socket and ectopic induced substantial cell homing into microchannels. (C) Combined SDF1 and BMP7 delivery homed
mineralization in human tooth scaf- significantly more cells into the microchannels than without growth-factor delivery (p < 0.01; N =
fold implanted into the dorsum. Our 11). (D) Combined SDF1 and BMP7 delivery elaborated significantly more blood vessels than
ongoing work has identified addi- without growth-factor delivery (p < 0.05; N = 11). (E,F) Mineral tissue in isolated areas in
tional growth factors that may con- microchannels adjacent to blood vessels and abundant cells, and confirmed by von Kossa staining.
(G) Tissue sections from coronal, middle, and two root portions of human molar scaffolds were
stitute an optimal conglomerate for
quantified for cell density and angiogenesis. s, scaffold; GF, growth factor(s). Scale: 100 µm.
tooth regeneration. Cell homing is
an under-recognized approach in tis-
sue regeneration (Mao et al., 2010), and offers an alternative to et al., 2009). The regenerated mandibular incisor-like structure was
cell-delivery-based tooth regeneration. Omission of cell isola- primarily the root with a portion of sub-occlusal crown. Further, no
tion and ex vivo cell manipulation may accelerate regulatory, attempt was made to regenerate enamel or dentin. Nonetheless, we
commercial, and clinical processes. The cost of tooth regenera- suggest that a regenerated tooth is biological primarily because of
tion by cell homing is not anticipated to be nearly as excessive its root, rather than the crown, which can be readily restored with a
as for cell delivery. clinical crown anchorable to a biologically regenerated root.
The present scaffold design represents a variation from pre- Regeneration of a putative periodontal ligament and new bone that
vious approaches in tooth regeneration by relying primarily on integrated with native alveolar bone appears to provide the ground
soft materials, including collagen gel, silk, or PLGA (e.g., for a clinically translatable approach. The present work does not
Young et al., 2002; Modino and Sharpe, 2005; Ikeda et al., preclude parallel studies of tooth regeneration by cell transplanta-
2009). Mechanical stiffness of PCL-HA hybrid is suitable for tion. Our recent work continues to explore regeneration of multiple
load-bearing (Woodfield et al., 2005). Among rapid prototyping tissues by cell delivery (Lee et al., 2009; Yang et al., 2010). One of
methods, 3D bioprinting offers the advantage of precise control the pivotal issues in tooth regeneration is to devise economically
of pore size, porosity, stiffness, and interconnectivity as well as viable approaches that are not cost-prohibitive and can translate
anatomic dimensions (Woodfield et al., 2005; Lee et al., 2009). into therapies for patients who cannot afford or are contra-indicated
Clinically, the patient’s healthy, contralateral tooth form can be for dental implants. Cell-homing-based tooth regeneration may
imaged by CT or MR, and then fed into a computer-aided design provide a tangible pathway toward clinical translation.
and a bioprinter to generate 3D scaffolds. Anatomically shaped
scaffolds can either be patient-specific or of generic sizes, and
made available as off-the-shelf implants in dental offices. ACKNOWlEDGMENTs
The present study, being the first of its kind for de novo forma-
tion of tooth-like tissues by cell homing, is not without limitations. We thank F. Guo and K. Hua for technical and administrative
All in vivo-harvested samples were embedded in PMMA, because assistance. This research was supported by NIH Grant 5RC2
PCL-HA cannot be decalcified for paraffin embedding. PMMA DE020767 from the National Institute of Dental and Craniofacial
embedding disallows immunoblotting by certain antibodies (Lee Research (NIDCR).
6. 6 Kim et al. J Dent Res X(X) XXXX
REFERENCEs Mantesso A, Sharpe P (2009). Dental stem cells for tooth regeneration and
repair. Expert Opin Biol Ther 9:1143-1154.
Abukawa H, Zhang W, Young CS, Asrican R, Vacanti JP, Kaban LB, et al. Mao JJ, Giannobile WV, Helms JA, Hollister SJ, Krebsbach PH, Longaker
(2009). Reconstructing mandibular defects using autologous tissue- MT, et al. (2006). Craniofacial tissue engineering by stem cells. J Dent
engineered tooth and bone constructs. J Oral Maxillofac Surg 67:335-347. Res 85:966-979.
Ahsan T, Bellamkonda R, Nerem RM (2007). Tissue engineering and regen- Mao JJ, Stosich MS, Moioli E, Lee CH, Fu S, Bastian B, et al. (2010). Facial
erative medicine: advancing toward clinical therapies. In: Translational reconstruction by biosurgery: cell transplantation vs. cell homing.
approaches in tissue engineering and regenerative medicine. Mao JJ, Tissue Eng Part B Rev [Epub ahead of print, March 8, 2010] (in press).
Vunjak-Novakovic G, Mikos AG, editors. Norwood, MA, USA: Artech Modino SA, Sharpe PT (2005). Tissue engineering of teeth using adult stem
House, Inc., pp. 3-16. cells. Arch Oral Biol 50:255-258.
Alhadlaq A, Mao JJ (2004). Mesenchymal stem cells: isolation and thera- Nait Lechguer A, Kuchler-Bopp S, Hu B, Haikel Y, Lesot H (2008).
peutics. Stem Cells Dev 13:436-448. Vascularization of engineered teeth. J Dent Res 87:1138-1143.
Belema-Bedada F, Uchida S, Martire A, Kostin S, Braun T (2008). Efficient Nakao K, Morita R, Saji Y, Ishida K, Tomita Y, Ogawa M, et al. (2007). The
homing of multipotent adult mesenchymal stem cells depends on development of a bioengineered organ germ method. Nat Methods
FROUNT-mediated clustering of CCR2. Cell Stem Cell 2:566-575. 4:227-230.
Crisan M, Chen CW, Corselli M, Andriolo G, Lazzari L, Peault B (2009). No Authors Given (2008). Evaluation criteria for musculoskeletal and cra-
Perivascular multipotent progenitor cells in human organs. Ann NY niofacial tissue engineering constructs: a conference report. Tissue Eng
Acad Sci 1176:118-123. Part A 14:2089-2104.
Duailibi MT, Duailibi SE, Young CS, Bartlett JD, Vacanti JP, Yelick PC Ohazama A, Modino SA, Miletich I, Sharpe PT (2004). Stem-cell-based
(2004). Bioengineered teeth from cultured rat tooth bud cells. J Dent tissue engineering of murine teeth. J Dent Res 83:518-522.
Res 83:523-528. Pihlstrom BL, Michalowicz BS, Johnson NW (2005). Periodontal diseases.
Duailibi SE, Duailibi MT, Zhang W, Asrican R, Vacanti JP, Yelick PC Lancet 366:1809-1820.
(2008). Bioengineered dental tissues grown in the rat jaw. J Dent Res Poole DFGI (1967). Structural and chemical organization of teeth. Vol.
87:745-750. I. Miles AEW, editor. New York, USA: Academic Press, pp. 111-
Ferreira CF, Magini RS, Sharpe PT (2007). Biological tooth replacement 149.
and repair. J Oral Rehabil 34:933-939. Rutherford B (2001). BMP-7 gene transfer to inflamed feret dental pulps.
Goldberg M, Six N, Decup F, Buch D, Soheili Majd E, Lasfargues JJ, et al. Eur J Oral Sci 109:422-424.
(2001). Application of bioactive molecules in pulp-capping situations. Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, et al. (2006).
Adv Dent Res 15:91-95. Mesenchymal stem cell-mediated functional tooth regeneration in
Hahn GV, Cohen RB, Wozney JM, Levitz CL, Shore EM, Zasloff MA, et al. swine. PLoS One 1:e79.
(1992). A bone morphogenetic protein subfamily: chromosomal local- Steinhardt Y, Aslan H, Regev E, Zilberman Y, Kallai I, Gazit D, et al. (2008).
ization of human genes for BMP5, BMP6, and BMP7. Genomics Maxillofacial-derived stem cells regenerate critical mandibular bone
14:759-762. defect. Tissue Eng Part A 14:1763-1773.
Herodin F, Bourin P, Mayol JF, Lataillade JJ, Drouet M (2003). Short-term Stosich MS, Moioli EK, Wu JK, Lee CH, Rohde C, Yoursef AM, et al.
injection of antiapoptotic cytokine combinations soon after lethal (2009). Bioengineering strategies to generate vascularized soft tissue
gamma-irradiation promotes survival. Blood 101:2609-2616. grafts with sustained shape. Methods 47:116-121.
Ikeda E, Morita R, Nakao K, Ishida K, Nakamura T, Takano-Yamamoto USDHHS (2005). Oral health in America: a report of the Surgeon General.
T, et al. (2009). Fully functional bioengineered tooth replacement as Rockville, MD: USDHHS, University Press of the Pacific.
an organ replacement therapy. Proc Natl Acad Sci USA 106:13475- Woodfield TB, Van Blitterswijk CA, De Wijn J, Sims TJ, Hollander AP,
13480. Riesle J (2005). Polymer scaffolds fabricated with pore-size gradients
Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (2001). as a model for studying the zonal organization within tissue-engineered
Promoting bone morphogenetic protein signaling through negative cartilage constructs. Tissue Eng 11:1297-1311.
regulation of inhibitory Smads. EMBO J 20:4132-4142. Xu WP, Zhang W, Asrican R, Kim HJ, Kaplan DL, Yelick PC (2008).
Kitaori T, Ito H, Schwarz EM, Tsutsumi R, Yoshitomi H, Oishi S, et al. Accurately shaped tooth bud cell-derived mineralized tissue formation
(2009). Stromal cell-derived factor 1/CXCR4 signaling is critical for on silk scaffolds. Tissue Eng Part A 14:549-557.
the recruitment of mesenchymal stem cells to the fracture site during Yang R, Chen M, Lee CH, Yoon R, Lal S, Mao JJ (2010). Clones of ectopic stem
skeletal repair in a mouse model. Arthritis Rheum 60:813-823. cells in the regeneration of muscle defects in vivo. PloS One (in press).
Kuo TF, Huang AT, Chang HH, Lin FH, Chen ST, Chen RS, et al. (2008). Yelick PC, Vacanti JP (2006). Bioengineered teeth from tooth bud cells.
Regeneration of dentin-pulp complex with cementum and periodontal Dent Clin North Am 50:191-203, viii.
ligament formation using dental bud cells in gelatin-chondroitin- Young CS, Terada S, Vacanti JP, Honda M, Bartlett JD, Yelick PC (2002).
hyaluronan tri-copolymer scaffold in swine. J Biomed Mater Res A Tissue engineering of complex tooth structures on biodegradable poly-
86:1062-1068. mer scaffolds. J Dent Res 81:695-700.
Lee CH, Marion NW, Scott HJ, Mao J (2009). Tissue formation and vascu- Young CS, Abukawa H, Asrican R, Ravens M, Troulis MJ, Kaban LB, et al.
larization of anatomically shaped human tibial condyle in vivo. Tissue (2005). Tissue-engineered hybrid tooth and bone. Tissue Eng 11:1599-
Eng Part A 15:3923-3930. 1610.