The Clinical Efficacy and Safety of ErhBMP-2/BioCaP/ß-TCP as a Novel Bone Substitute Using the Tooth-Extraction-Socket-Healing Model: A Proof-of-Concept Randomized Controlled Trial.

AIM: This first randomized controlled trial in humans aimed to assess the efficacy and safety of low-dosage Escherichia coli-derived recombinant human bone morphogenetic protein 2 (ErhBMP-2)-incorporated biomimetic calcium phosphate coating-functionalized ß-TCP (ErhBMP-2/BioCaP/ß-TCP) as a novel bone substitute using the tooth-extraction-socket-healing model. MATERIALS AND METHODS: Forty patients requiring dental implants after single-root tooth extraction were enrolled in this study and randomly assigned into three groups: ErhBMP-2/BioCaP/ß-TCP (N = 15), ß-TCP (N = 15) and natural healing (N = 10). New bone volume density from histomorphometric analyses was evaluated 6 weeks post-operatively as the primary outcome, and other histomorphometric analyses, alveolar bone and soft-tissue changes were the secondary outcomes. Safety parameters included adverse events, soft-tissue healing, oral health impact profile, serum BMP-2 concentrations and other laboratory tests. RESULTS: The findings revealed a significant increase in new bone volume density in patients treated with ErhBMP-2/BioCaP/ß-TCP compared to those receiving ß-TCP alone. The required bone augmentation procedures during implant placement surgery in the ErhBMP-2/BioCaP/ß-TCP group were significantly less than in the natural healing group. There were no significant differences in safety parameters among the three groups. CONCLUSION: This clinical trial primarily proved the safety and efficacy of ErhBMP-2/BioCaP/ß-TCP as a promising bone substitute.

Role of sclerostin deletion in bisphosphonate-induced osteonecrosis of the jaw.

PURPOSE: Bone resorption inhibitors, such as bisphosphonates (BP) and denosumab, are frequently used for the management of osteoporosis. Although both drugs reduce the risk of osteoporotic fractures, they are associated with a serious side effect known as medication-related osteonecrosis of the jaw (MRONJ). Sclerostin antibodies (romosozumab) increase bone formation and decrease the risk of osteoporotic fractures: however, their anti-resorptive effect increases ONJ. Thus, this study aimed to elucidate the role of sclerostin deletion in the development of MRONJ. METHODS: Sclerostin knockout (SostΔ26/Δ26) mice were used to confirm the development of ONJ by performing tooth extractions. To confirm the role of sclerostin deficiency in a more ONJ-prone situation, we used the BP-induced ONJ model in combination with severe periodontitis to evaluate the development of ONJ and bone formation in wild-type (WT) and SostΔ26/Δ26 mice. Wound healing assay using gingival fibroblasts with or without sclerostin stimulation and tooth extraction socket healing were evaluated in the WT and SostΔ26/Δ26 mice. RESULTS: ONJ was not detected in the extraction socket of SostΔ26/Δ26 mice. Moreover, the incidence of ONJ was significantly lower in the SostΔ26/Δ26 mice treated with BP compared to that of the WT mice. Osteogenic proteins, osteocalcin, and runt-related transcription factor 2, were expressed in the bone surface in SostΔ26/Δ26 mice. Recombinant sclerostin inhibited gingival fibroblast migration. The wound healing rate of the extraction socket was faster in SostΔ26/Δ26 mice than in WT mice. CONCLUSION: Sclerostin deficiency did not cause ONJ and reduced the risk of developing BP-induced ONJ. Enhanced bone formation and wound healing were observed in the tooth extraction socket. The use of romosozumab (anti-sclerostin antibody) has proven to be safe for surgical procedures of the jaw.

Evaluation of 4 and 8 Weeks of Healing in a Murine Implant Model.

Dental implants are increasing in prevalence as desirable options for replacing missing teeth. Unfortunately, implants come with complications, and animal models are crucial to studying the pathophysiology of complications. Current murine model experiments can be lengthy, with 8 weeks of extraction socket healing before implant placement. Therefore, we aimed to investigate the efficacy of decreasing extraction healing time from 8 to 4 weeks in a dental implant mouse model. Thirty-one 3-week-old C57BL/6J male mice underwent maxillary first and second molar extractions followed by 8 (control) or 4 (test) weeks of extraction socket healing before implant placement. Mice were euthanized after 4 weeks of implant osseointegration. Samples were analyzed via microcomputerized tomography and histology. When mice received implants 4 weeks after extractions, there was no statistical difference in initial bone crest remodeling or surrounding bone volume compared to those after 8 weeks of healing. Histologically, the hard and soft tissues surrounding both groups of implants displayed similar alveolar bone levels, inflammatory infiltrate, osteoclast count, and collagen organization. A 4-week extraction healing period can be utilized without concern for osseointegration in a murine implant model and is a viable experimental alternative to the previous eight weeks of healing. While small animal implant models are less directly applicable to humans, advancements in experimental methods will ultimately benefit patients receiving dental implants through improved prevention and treatment of complications. Subsequent research could investigate occlusal effects or whether healing time affects prognosis after induction of peri-implantitis.

Kangfuxin Accelerates Extraction Socket Healing by Promoting Angiogenesis Via Upregulation of CCL2 in Stem Cells.

Kangfuxin (KFX) shows potential in wound healing, but its role in socket healing is unclear. This research finds increased bone mass, mineralization, and collagen deposition in KFX-treated mice. Mouse bone marrow mesenchymal stem cells, human periodontal ligament stem cells (hPDLSCs), and human dental pulp stem cells (hDPSCs) are treated with KFX under osteogenic induction. RNA-sequencing reveals upregulated chemokine-related genes, with a threefold increase in chemokine (C-C motif) ligand 2 (Ccl2). The conditioned medium (CM) of hPDLSCs and hDPSCs treated with KFX promotes endothelial cell migration and angiogenesis. Ccl2 knockdown abolishes CM-induced endothelial cell migration and angiogenesis, which can be reversed by recombinant CCL2 treatment. KFX-treated mice showed increased vasculature. In conclusion, KFX increases the expression of CCL2 in stem cells, promoting bone formation and mineralization in the extraction socket by inducing endothelial cell angiogenesis. © 2023 American Society for Bone and Mineral Research (ASBMR).

Improved access to the bone marrow space by multiple perforations of the alveolar bundle bone after tooth extraction-A case report.

OBJECTIVES: The dental alveolus is lined by a thin cortical layer ("bundle bone", "alveolar bone proper", "cribriform plate", "lamina dura"), that can impede access to the bone marrow and its vasculature. During unassisted socket healing, the alveolar bundle bone is gradually resorbed allowing tissue resources from the bone marrow to enter into the socket space. An optimized wound healing process, either during unassisted socket healing or during ridge preservation procedures, with autogenous bone and/or any bone/collagen substitute material, depends at least partly on an adequate vascularization of the socket space. This ensures sufficient recruitment of osteoblast and osteoclast precursor cells and facilitates fast bone regeneration and/or uneventful integration of the augmentation material. METHODS: The present technical note describes an easy treatment step after tooth extraction aiming to improve socket healing with or without any ridge preservation procedure, by facilitating an increased blood inflow into the dental alveolus. Specifically, after tooth extraction the alveolar bundle bone is perforated several times - mainly in a palatally/lingually - by a small round bur (diameter < 1 mm) extending into the trabecular bone. RESULTS AND CONCLUSIONS: By means of this relatively simple treatment step, an increased blood inflow into the alveolus is achieved after tooth extraction, which might enhance socket healing and corticalization of the entrance, and in turn result in a lower complication rate (e.g., dry socket), in an enhanced graft incorporation, and/or in a reduced loss of alveolar ridge volume.

Endodontic remnants are found more than other radiopacities in proposed implant sites.

BACKGROUND: Foreign bodies may be a cause of concern in dental implant failure. PURPOSE: The aim of the present study was to assess the occurrence and to evaluate the types of radiopacities in dental extraction sites using cone beam computed tomography (CBCT). MATERIALS AND METHODS: The incidence, location, and types of radiopacities were evaluated in 180 CBCT scans. RESULTS: Different radiopaque structures could be noted in 84 scans. Foreign bodies and remaining roots were frequently seen. Most of the radiopacities were attributed to remaining endodontic filling in upper and lower jaws in 25 scans in different locations. Remaining roots could be detected in 20 scans. Focal and diffuse radiopaque bony lesions were observed in 16 scans. Tissue response in the form of radiolucency could be seen more with endodontic foreign bodies. Tissue reactions to radiopaque filling remnants were seen in 6.11% of cases. CONCLUSIONS: Foreign body remnants, mostly of endodontic fillings, were frequently seen in CBCT in upper and lower jaws. Evidence of tissue reactions to extraction remnants could be found. Endodontic filling remnants could be seen more in the upper jaw. Thorough examination of implant site for the presence of endodontic foreign body remnants should be stressed. Debridement of the extraction socket should be done carefully in endodontically treated teeth.

Influence of ridge preservation procedures on extraction socket healing under antiresorptive therapy: An experimental study in rabbits.

BACKGROUND: To assess the influence of ridge preservation procedures on the healing of extraction sockets under antiresorptive therapy. MATERIAL AND METHODS: A total of 10 Dutch Belted rabbits were randomly allocated to either the intravenous administration of amino-bisphosphonate (zoledronic acid) (Za) (n = 5) or a negative control group (no Za [nZa]) (n = 5). At 6 months, the mandibular and maxillary molars were extracted and the four experimental sites randomly allocated to the following subgroups: (a) socket grafting using a collagen-coated natural bone mineral (BOC) + primary wound closure, (b) coronectomy (CO), or (c) spontaneous healing + primary wound closure (SP). Za medication was continued for another 4 months. Histomorphometrical analyses considered, for example, crestal hard tissue closure of the extraction site (C) and mineralized tissue (MT) formation. RESULTS: Za-SP was associated with an incomplete median C (31.76% vs 100% in nZa-SP) and signs of bone arrosion along the confines of the socket. BOC had no major effects on increases in C and MT values in the Za group. CO commonly resulted in an encapsulation and partial replacement resorption of residual roots by MT without any histological signs of osteonecrosis. CONCLUSIONS: (a) Za-SP was commonly associated with a compromised socket healing and signs of osteonecrosis, (b) BOC had no major effect on socket healing in the Za group, and (c) CO at noninfected teeth might be a feasible measure for the prevention of a Za-related osteonecrosis of the jaw.

Mandibular trabecular structures in alveolar ridge preservation using different grafting materials after tooth extraction / Estructura trabecular mandibular en preservación de reborde alveolar utilizando diferentes materiales de injerto después de la exodoncia

The aim was to describe the star volume analysis in ridge preservation using different grafting materials. Bilateral extraction of the first mandibular molars of sixteen male rabbits was performed, divided at random into four groups (n= 4 in each group) according to graft, using: blood clot (G1), xenograft (G2), pure phase beta-tricalcium phosphate (G3) and biphasic calcium phosphate (60 % HA / 40 % beta-TCP) (G4). Rabbits were euthanized at 4, 6, or 8 wk post-extraction; the trabecular bone structures was evaluated by star volume analysis. The Levene test was used to analyze variance, as was the independent sample t-test. A P-value of < 0.001 was used to establish a statistically significant. The star volume analysis of the mandibular trabecula shows that the marrow space star volume (V*m.space) was higher than the trabecular star volume (V*tr). At 6-week post-extraction, new trabecular bone was evident. At 8-week post-extraction V*tr increase in all groups and the V*m.space diminish, suggesting coarsening of the internal architecture. In G2, some trabecular bone was observed in the central region. In G3, most of the socket regions were occupied by newly formed and loose trabecular bone and in the G4, the sockets were almost entirely filled with trabecular bone. Star volume analysis is adequate to analysis of bone patterns formation using bone substitutes.

El objetivo de esta investigación fue describir el volumen estrella en preservación alveolar utilizando diferentes injertos óseos. La exodoncia bilateral del primer molar mandibular de 16 conejos machos fue realizada, dividiéndolos en 4 grupos (n= 4 en cada grupo) de acuerdo al injerto utilizado, siendo: coágulo sanguíneo (G1), xenoinjerto (G2), beta-tricalcio fosfato puro (G3) y fosfato de calcio bifásico (60 % HA / 40 % beta-TCP) (G4). Los conejos fueron sometidos a eutanasia a las 4, 6 u 8 semanas post exodoncia; el trabeculado óseo fue evaluado por medio del volumen estrella. La prueba de Levene fue utilizado para el análisis de varianza y luego la prueba t-test para muestras independientes. El valor de P menor a 0.001 fue establecido como significancia estadística. El análisis del volumen estrella del trabeculado mostró que el espacio medular de volumen estrella (V*m.space) fue mayor que trabeculado (V*tr). A 6 semanas post exodoncia, nuevo trabeculado óseo fue evidente. A las 8 semanas post exodoncia V*tr aumenta en todos los grupos y el V*m.space disminuye, sugiriendo un engrosamiento de la arquitectura interna. En el grupo G2, algún trabeculado óseo fue observado en la región central. En el G3, la mayoría del alveolo fue ocupado por nuevo hueso y perdió trabeculado óseo y en G4, el alveolo fue ocupado casi enteramente por hueso trabecular. El análisis de volumen estrella es adecuado para analizar el modelo de formación ósea utilizando sustitutos óseos.

Molecular, Cellular and Pharmaceutical Aspects of Filling Biomaterials During the Management of Extraction Sockets.

After a tooth extraction both hard and soft tissues undergo dimensional changes. The use of a ridge preservation technique at the moment of the tooth extraction could help could help to prevent the volume loss, thus simplifying the subsequent prosthetic and/or implant therapy. Some studies were conducted in order to examine the biomaterials and the surgical technique used for ridge preservation procedures. Clinical, histological, volumetric and molecular outcomes were registered and analyzed in different studies, in order to comprehend the biological events and the consequences of a socket preservation procedure and to allow the clinician to make the correct choice.

High-Frequency, Low-Intensity Pulsed Ultrasound Enhances Alveolar Bone Healing of Extraction Sockets in Rats: A Pilot Study.

Most studies of the beneficial effects of low-intensity pulsed ultrasound (LIPUS) on bone healing have used frequencies between 1.0 and 1.5 MHz. However, after consideration of ultrasound wave characteristics and depth of target tissue, higher-frequency LIPUS may have been more effective on superficially positioned alveolar bone. We investigated this hypothesis by applying LIPUS (frequency, 3.0 MHz; intensity, 30 mW/cm(2)) on shaved right cheeks over alveolar bones of tooth extraction sockets in rats for 10 min/d for 2 wk after tooth extraction; the control group (left cheek of the same rats) did not receive LIPUS treatment. Compared with the control group, the LIPUS group manifested more new bone growth inside the sockets on histomorphometric analysis (maximal difference = 2.5-fold on the seventh day after extraction) and higher expressions of osteogenesis-related mRNAs and proteins than the control group did. These findings indicate that 3.0-MHz LIPUS could enhance alveolar bone formation and calcification in rats.

The Effects of Topical Hemocoagulase Solution on the Healing Process of Post-extraction Wounds: A Split Mouth Design.

OBJECTIVES: To evaluate the effects of topical hemocoagulase on intra-oral extraction sockets and impact on the healing process as well as to produce a clinico-histological healing score. STUDY DESIGN: This prospective study compared two extraction sites in each subject. One site received topical hemocoagulase while other site did not receive it. Both the sites were chosen in the same patient and extraction was done at separate intervals. The biopsy was done on a random basis with the pathologist being blinded to the study. Clinical evaluation was done on days 7, 14 and 21. Biopsy was done either on days 7 or 14 for the case as well as for the control. A clinical as well as histological score was developed and the healing was assessed. Statistical analysis was done using Wilcoxon signed rank test and p value ≤ 0.05 was considered significant and z-score was also calculated. RESULTS: The clinical score did not show any statistical significance. The histological total score on day 14 and combined overall analysis of days 7 and 14 showed statistical significance. There was an increased incidence (n = 4) of osteoid formation in the hemocoagulase group on day 14. CONCLUSION: The application of hemocoagulase may improve and accelerates the process of wound healing in extraction sockets.

Alveolar ridge preservation with a free gingival graft in the anterior maxilla: volumetric evaluation in a randomized clinical trial.

The aim of this study was to evaluate and compare the dimensional changes in maxillary extraction sockets that have healed spontaneously and those treated with free gingival grafts. Ten subjects with at least two maxillary anterior teeth scheduled for extraction were selected for this study. Two maxillary teeth were allocated randomly to either the test group or the control group. In the test group, the extraction socket was covered with a free gingival graft harvested from the palate, while in the control group the sockets healed spontaneously. Cone beam computed tomography (CBCT) scans were taken on the day of extraction and at 3 months postoperative. Soft tissue healing of the extraction sockets was assessed visually by clinical inspection. Hard tissue measurements were obtained from the CBCT scans. After 3 months of healing, the control sockets had lost height in the buccal and lingual crestal bones (-1.03 and -0.56mm, respectively); however, the height in the buccal and lingual crestal bones was preserved at the test sites (+0.06 and +0.25mm, respectively). This difference between the two groups was statistically significant (P<0.05). In contrast, both the control and test groups lost width in the buccal and lingual crestal bones; the difference between the control and test groups was not statistically significant (P>0.05). The authors propose that covering the orifice of the extraction socket with a free gingival graft can result in preservation of the alveolar bone height.