Dental stem cell therapy with calcium hydroxide in dental pulp capping

Calcium hydroxide has been extensively and steadily used for direct pulp capping in modern clinical dentistry. As it was known to have potential to induce hard tissue repair, this chemical has been applied to the exposed dental pulp and the hard tissue is expected to be regenerated above the pulp. During the reparative process of exposed pulp, primary odontoblasts that were lost as a result of extensive damage are replaced with newly differentiated odontoblast-like cells. This process is known to follow the sequential steps of proliferation, migration, and differentiation of progenitor cells. This research will examine the relationship between calcium hydroxide and the recruitment, proliferation, and mineralization of postnatal dental stem cells, obtained from an immature dental tissue of beagle dogs. Immunocytochemical staining and reverse transcriptase-polymerase chain reaction were used to identify the putative stem cell markers. Immunoblot analysis, wound healing assay, cell migration assay, and alizarin red staining were used to evaluate proliferation, migration, and mineralization capacity of the calcium hydroxide-treated stem cells. As an in vivo study, a combination of calcium hydroxide and autologous dental pulp stem cells (DPSCs) was applied for the treatment of intentionally created tooth defects on the premolars and the molars in beagle dogs to observe dentin regeneration. Ex vivo expanded DPSCs and periodontal ligament stem cells expressed STRO-1 and CD146, the mesenchymal stem cell markers. It was evident that calcium hydroxide increased recruitment, migration, proliferation, and mineralization of the DPSCs and periodontal ligament stem cells. Such results are valuable for future availability of DPSCs, which are recently focused as the stem cell reservoir for regeneration of dentin upon tooth injury, as well as for elucidation of the role of calcium hydroxide in pulp capping therapy.This work was supported by grants from the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. 2009-0066366) to Pill-Hoon Choung and by the Ministry of Health and Welfare, the Republic of Korea, through the Musculoskeletal Bioorgans Center Program (no. 0405-BO01-0204-0006)

Stem Cell Property of Postmigratory Cranial Neural Crest Cells and Their Utility in Alveolar Bone Regeneration and Tooth Development

The vertebrate neural crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory cranial neural crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-β signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures

Molecular Responses in Osteogenic Differentiation of Mesenchymal Stem Cells Induced by Physical Stimulation

Mesenchymal stem cells (MSCs) have been recognized as a great source of stem cells in the field of regenerative medicine and regulation of MSCs such as differentiation into specific cells. Particular interest is the use of physical stimulation for the expression of the osteoblast-specific genes from MSCs for bone tissue regeneration. The mechanical forces on MSCs, such as fluid flow, enhance the mineralized matrix and specific gene expressions. This process called mechanotransduction comprises of the steps of mechanoreception, biochemical coupling, transmission of signal and effector cell response. Physical stimuli effectively regulate extracellular and intracellular signaling pathways to enhance the expression of specific transcription factors, and the release of osteocytes, ultimately expedite the production of active osteoblasts. Thus understating, identification and functional characterization of the mechanotransduction underlying the physical stimulation of MSCs is a critical issue for devising new bone regenerative treatments for bone-related diseases. In this review, we focus on the molecular mechanism responsible for the mechanotransduction of osteogenic differentiation of MSCs induced by physical stimulation.

Quantification of three-dimensional facial asymmetry for diagnosis and postoperative evaluation of orthognathic surgery

Abstract Background To evaluate the facial asymmetry, three-dimensional computed tomography (3D-CT) has been used widely. This study proposed a method to quantify facial asymmetry based on 3D-CT. Methods The normal standard group consisted of twenty-five male subjects who had a balanced face and normal occlusion. Five anatomical landmarks were selected as reference points and ten anatomical landmarks were selected as measurement points to evaluate facial asymmetry. The formula of facial asymmetry index was designed by using the distances between the landmarks. The index value on a specific landmark indicated zero when the landmarks were located on the three-dimensional symmetric position. As the asymmetry of landmarks increased, the value of facial asymmetry index increased. For ten anatomical landmarks, the mean value of facial asymmetry index on each landmark was obtained in the normal standard group. Facial asymmetry index was applied to the patients who had undergone orthognathic surgery. Preoperative facial asymmetry and postoperative improvement were evaluated. Results The reference facial asymmetry index on each landmark in the normal standard group was from 1.77 to 3.38. A polygonal chart was drawn to visualize the degree of asymmetry. In three patients who had undergone orthognathic surgery, it was checked that the method of facial asymmetry index showed the preoperative facial asymmetry and the postoperative improvement well. Conclusions The current new facial asymmetry index could efficiently quantify the degree of facial asymmetry from 3D-CT. This method could be used as an evaluation standard for facial asymmetry analysis

Vascularized bone flap for access on the maxillary sinus

This article describes a vascularized bony window for access to the maxillary sinus and reports the clinical results. A bony U-shaped window in the anterior sinus wall was pedicled on the surrounding soft tissue and periosteum. After the described sinus was cleared of disease, the window was repositioned in its original site either using resorbable sutures or not. The method was used in 47 maxillary sinus operations in 45 patients. Twenty-four patients were followed-up for more than 48 months. The vascularized bony window technique showed uneventful healing in all patients and none of the 24 patients reported any problems. The vascularized bony window technique provides a large antrostomy, which gives good access and visibility and results in satisfactory postoperative healing

The Auriculomastoid Fasciocutaneous Island Flap: A New Flap for Orofacial Reconstruction

Various designs for previously reported postauricular skin flaps have the disadvantages of being two-stage procedures, providing a limited pedicle, or requiring microvascular anastomoses. To overcome such problems, a new auriculomastoid fasciocutaneous (AMFC) island flap for orofacial reconstruction has been developed. This article presents the technique and reports the clinical results. A long ipsilateral AMFC island flap pedicled by the parietotemporal fascia and based on the parietal branches of the superficial temporal artery, the occipital artery, and the postauricular artery was designed. Twenty-five of these island flaps were used to reconstruct intraoral or external facial defects. The fasciocutaneous flap could be extended to reach any orofacial defect as a single or compound design in a one-stage subcutaneous procedure. Compound types of AMFC island flaps, including scalp, parietal bone, or the parietotemporal fascia were performed successfully based on single vessels. The flaps survived well on poorly vascularized underlying tissues, except for one case. The flap has the characteristics of providing thin and pliable skin, a good color match to the face, and restored sensitivity. The donor defect is designed to be closed directly and concealed behind the ear without ear deformity. This flap is very useful in orofacial reconstruction because the skin quality equals that of the radial forearm flap, without the need for microvascular anastomoses, with many additional advantages and various modifications of design

An intraoral approach to treatment of condylar hyperplasia or high condylar process fractures using the intraoral verticosagittal ramus osteotomy

Purpose: The intraoral vertico-sagittal ramus osteotomy (J Craniomaxillofac Surg 20:153, 1992) can be used to reduce high condylar process fractures and recontour hyperplastic condyles while simultaneously correcting the malocclusion. This article presents the technique and reports the clinical results. Patients and Methods: A technique for removal and replantation of the condyloid process using the vertico-sagittal ramus osteotomy and rigid fixation was used to treat 23 patients with markedly displaced, high condylar process fractures and condylar hyperplasia associated with malocclusion. Results: The replanted condyles did not show ischemic necrosis or any functional disturbance when followed for more than 3 years. All patients showed nearly normal mouth opening, with slight mandibular deviation, usually in sixth postoperative month. Conclusions: In selected patients, this technique allows intraoral accessibility to the condyle and its repositioning. The method is particularly useful to treat vertical discrepancies associated with the hyperplastic or hypoplastic condyle

The coronoid process for paranasal augmentation in the correction of midfacial concavity

Objective: The coronoid process can be easily harvested as a donor bone by an intraoral approach during orthognathic surgery, especially during mandibular ramus surgery. This study was performed to provide an objective assessment of the coronoid process as a candidate material for paranasal augmentation. Study Design: The dimensions of the coronoid process and the paranasal area were directly measured in 15 dry skulls. Based on these data, the coronoid process was used for a paranasal augmentation in 54 patients. Results: The size and shape of the coronoid process was found suitable for paranasal augmentation; its thickness was 5.4 ± 0.8 mm on the right and 5.8 ± 1.2 mm on the left. All patients showed improved facial esthetics without complications when followed up for more than 12 months. Conclusion: The coronoid process seems to be suitable for paranasal augmentation in the dry skull study. Its clinical application is also favorable because its size and morphology fits into the paranasal region, with the additional advantages of biocompatibility, availability, and reduced operation time for harvesting. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:28-33

Effects of a bisphosphonate on the expression of bone specific genes after autogenous free bone grafting in rats.

The purpose of this study was to evaluate the clinical availability of a bisphosphonate in autogenous free bone grafts. Bisphosphonate (0.01 mg/kg/day) was administered daily after an autogenous free bone graft on a rat calvarium. The effects of a bisphosphonate on the resorption of grafted bone and mRNA expression in bone specific genes, i.e. bone morphogenetic protein 2, bone morphogenetic protein 4, alkaline phosphatase, osteocalcin, osteoclast inhibitory factor and calcitonin receptor, were studied via a reverse transcription‐polymerase chain reaction (RT‐PCR), real time RT‐PCR and tartrate‐resistant alkaline phosphatase (TRAP) staining. In a clinical and histomorphological review, bone resorption decreased in the experimental group in contrast to the control group where active bone resorption was observed. Bisphosphonate altered not only the mRNA expression of the bone resorption associated genes but also the bone formation associated genes. The expression of the calcitonin receptor (CTR) mRNA was not detected and the osteoclast inhibitory factor (OCIF) was significantly up‐regulated in the experimental group as opposed to the control group. The expressions of osteocalcin and alkaline phosphatase mRNAs were also higher in the experimental group. However, there was no significant difference in the mRNA expression of bone morphogenetic proteins between the two groups. The data suggest the possibility of a clinical application of bisphosphonates for decreasing resorption of grafted boneThis study was supported in part by a grant of the Korea Health 21 R & D project, Ministry of Health & Welfare (HMP- 00-CH-11-0010). We would like to thank Seong-Doo Hong and Hyun-Kyung Bae, oral pathologists in our hospital, for their helpful suggestions and examination of histological features in this study