Effects of systemic ozone administration on the fresh extraction sockets healing: a histomorphometric and immunohistochemical study in rats.

OBJECTIVE: Studies have highlighted numerous benefits of ozone therapy in the field of medicine and dentistry, including its antimicrobial efficacy against various pathogenic microorganisms, its ability to modulate the immune system effectively, reduce inflammation, prevent hypoxia, and support tissue regeneration. However, its effects on dental extraction healing remain to be elucidated. .Therefore, this study aimed to evaluate the effects of systemically administered ozone (O3) at different doses in the healing of dental extraction sockets in rats. METHODOLOGY: To this end, 72 Wistar rats were randomly divided into four groups after extraction of the right upper central incisor: Group C - control, no systemic treatment; Group OZ0.3 - animals received a single dose of 0.3 mg/kg O3; Group OZ0.7 - a single dose of 0.7 mg/kg O3; and Group OZ1.0 - a single dose of 1.0 mg/kg O3, intraperitoneally. In total, six animals from each group were euthanized at 7, 14, and 21 days after the commencement of treatment. Bone samples were harvested and further analyzed by descriptive histology, histomorphometry, and immunohistochemistry for osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) protein expression. RESULTS: All applied doses of O3 were shown to increase the percentage of bone tissue (PBT) after 21 days compared to group C. After 14 days, the OZ0.7 and OZ1.0 groups showed significantly higher PBT when compared to group C. The OZ1.0 group presented the most beneficial results regarding PBT among groups, which denotes a dose-dependent response. OCN immunostaining was higher in all groups at 21 days. However, after seven and 14 days, the OZ1.0 group showed a significant increase in OCN immunostaining compared to C group. No differences in TRAP+ osteoclasts were found between groups and time points. CONCLUSION: Therefore, O3 therapy at higher doses might be beneficial for bone repair of the alveolar socket following tooth extraction.

The effects of sodium alendronate on socket healing after tooth extraction: a systematic review of animal studies.

The aim of this systematic review was to answer the following question: "Does alendronate, a nitrogen-containing bisphosphonate, improve or impair alveolar socket healing after tooth extraction in animal models"? To this end, a systematic review of the literature was carried out in PubMed, Scopus, LILACS, Web of Science, as well as in the gray literature up to May 2023. Preclinical studies that evaluated alveolar healing after tooth extraction and the intake of sodium alendronate compared with placebo were included. Two investigators were responsible for screening the articles independently, extracting the data, and assessing their quality through the SYRCLE's RoB tool for randomized trials in animal studies. The study selection process, study characteristics, risk of bias in studies, impact of alendronate on bone healing, and certainty of evidence were described in text and table formats. Methodological differences among the studies were restricted to the synthesis methods. The synthesis of qualitative results followed the Synthesis Without Meta-analysis (SWiM) reporting guideline. From the 19 included studies, five were considered to have low risk, three were of unclear risk, and eleven presented a high risk of bias. The studies were considered heterogeneous regarding alendronate posology, including its dosage and route of administration. Furthermore, a variety of animal species, different age ranges, diverse teeth extracted, and exposure or not to ovariectomy contributed to the lack of parity of the selected studies. Our results indicated that alendronate monotherapy negatively affects the early phase of wound healing after tooth extraction in preclinical studies, suggesting that the bone resorption process after tooth extraction in animals treated with alendronate might impair the bone healing process of the extraction socket. In conclusion, alendronate administration restrains bone resorption, thereby delaying alveolar socket healing . Future studies should be conducted to validate these findings and to better understand the effects of alendronate therapy on oral tissues.

Transplantation of bone marrow mesenchymal stem cells and fibrin glue into extraction socket in maxilla promoted bone regeneration in osteoporosis rat.

AIMS: Bone defect repair in osteoporosis remains a tremendous challenge for clinicians due to increased bone metabolism resulted from estrogen deficiency. This study aims to investigate the effect of bone marrow mesenchymal stem cells (BMSCs) combined with fibrin glue (FG) in the extraction socket healing process of osteoporosis rats, as well as estimate the role of estrogen receptors (ERs) played in BMSCs differentiation in vitro and in the alveolar bone reconstruction process in vivo. MAIN METHODS: Forty rats were randomly divided into four groups, under general anesthesia, three groups underwent bilateral ovariectomy(OVX) and one group with the sham operation. Three months later, the osteogenic ability of BMSCs, isolated from healthy and osteoporosis rats, respectively, was tested. The ERα and ERß mRNA expression in BMSCs was also evaluated by RT-PCR analysis. In vivo experiment, Micro-CT detection, histological and immunofluorescent analysis, tissue PCR was conducted up to 2, 4 and 6 weeks after transplantation of BMSCs/FG to assess the newly formed bone in the extraction socket. KEY FINDINGS: The BMSCs from osteoporosis rats displayed weaker osteogenic potential and lower ERs expression compared with the BMSCs from healthy rats. Newly formed bone tissue filled the socket defect in BMSCs/FG treated VOX rats after six weeks, which was comparable to the sham group, while reduced ERs expression was found in the regenerated bone of the OVX group. SIGNIFICANCE: The BMSCs seeded within FG might provide an alternative therapeutic method for repairing the extraction socket defect in osteoporosis condition.

Effects of Soft Tissue Closure on Medication-Related Osteonecrosis of the Jaw in a Rabbit Model with Tooth Extraction: A Pilot Study.

OBJECTIVES: The study investigated the effect of soft tissue closure after tooth extraction on the prevention of medication-related osteonecrosis of the jaw in a rabbit model. MATERIALS AND METHODS: Twenty female New Zealand white rabbits were randomly assigned into the experimental group administrated with zoledronic acid (ZA) and control groups treated with saline. Bilateral lower premolar extraction was performed 4 weeks after ZA/saline administration. Immediately after extraction, the wound on the right mandible was closed by suture while the other side was left open. Animals were sacrificed 4 weeks and 8 weeks after tooth extraction. Fluorochrome labeling solutions were injected subcutaneously to evaluate the bone growth rates. The mandibles were harvested and subjected for microcomputed tomography, confocal microscope, and histomorphological examinations. RESULTS: All extraction sites healed well without any signs of infection. Trabecular thickness (Tb.Th) was significantly higher in the ZA-treated group than in the control group at both week 4 and week 8, while no significant difference was detected in the rest of the assessed parameters. The bone growth rate in mandibles showed gradual reduction in the ZA-treated group. Histological analysis showed that at week 8, the animals in the ZA-treated group had significantly higher incidence of osteonecrosis than that in the control group, while no significance was revealed between the sutured and nonsutured side. CONCLUSIONS: ZA treatment significantly reduces bone growth rates but does not reveal a significant effect on bone mineral density and bone microarchitecture. Soft tissue closure of the extraction socket does not reduce the incidence of ONJ in the ZA-treated rabbit model.

Short-Term Evaluation of Guided Bone Reconstruction with Titanium Mesh Membranes and CGF Membranes in Immediate Implantation of Anterior Maxillary Tooth.

PURPOSE: The aim of the present prospective study was to evaluate the effect of titanium mesh and concentrated growth factor (CGF) membranes in reconstructing severe labial bone defects during immediate implantation of anterior maxillary tooth. METHODS: Patients with severe defects presenting on the anterior labial bone plate of maxillary were enrolled in this study. During immediate implantation, the titanium mesh was used to maintain the space of bone graft, collagen membrane, and xenograft bone that were used to guide bone regeneration (GBR). Cone beam computed tomography (CBCT) was used to measure the height and the labial bone thickness around the implant at the time of the second stage surgery, 6 months, 1 year, and 2 years after restoration. The pink esthetic score (PES) was used to evaluate the esthetic outcomes after restoration. RESULTS: 18 patients were enrolled in this study. The survival rate of implants was 100%, and no complication was observed, except for 1 case of titanium mesh exposure which did not affect osteogenesis. In the second stage of surgery, the labial bone was completely reconstructed, and the top of the implant was covered with a small amount of new bone. The thickness of the labial bone was 3.01 mm (±0.23), 2.96 mm (±0.21), 2.93 mm (±0.19), and 2.92 mm (±0.16) at the time of the second stage surgery, 6 months, 1 year, and 2 years after restoration, respectively. The height of the marginal bone around implants was above the top of implant at the time of the second stage surgery and then reduced 0.72 mm (±0.07), 0.91 mm (±0.08), and 0.90 mm (±0.07) at the time point of 6 months, 1 year, and 2 years after restoration, respectively. The changes of bone thickness and height were statistically significant within one year, but stable after one year. The PES values showed the same tendency. CONCLUSIONS: With the limitation of the present prospective study, the combination of titanium mesh and CGF membrane could provide space maintenance for bone augmentation of alveolar bone defects and improve the bone regeneration in patients with severe labial bone defect when immediate implant of anterior maxillary.

Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid.

This study investigated the role 5-lypoxigenase (5-LO) on alveolar socket healing in aged female mice treated with zoledronic acid (ZL). Forty 129/Sv female mice (64-68 weeks old), 20 wild type (WT) and 20 5-LO knockout (5LOKO) were equally distributed according to ZL treatment: WT Control, WT ZL, 5LOKO Control, and 5LOKO ZL. ZL groups were treated with an intraperitoneal injection of 250 µg/Kg of ZL, while controls were treated with saline. Treatments were administered once a week, starting four weeks before surgery for tooth extraction and until 7 and 21 days post-surgery. Mice were euthanized for a comprehensive microscopic analysis (microCT, histomorphometry and immunohistochemistry). WT ZL mice presented intense inflammatory infiltrate (7 days), delayed bone formation (21 days), reduced collagenous matrix quality, and a deficiency in Runx-2 + , TRAP + , and macrophages as compared to controls. 5LOKO ZL animals presented decreased number of Runx-2 + cells in comparison to 5LOKO Control at 7 days, but no major changes in bone healing as compared to WT or 5LOKO mice at 21 days. The knockout of 5LO favored intramembranous bone healing in aged female mice, with a direct impact on inflammatory response and bone metabolism on the development of ONJ-like lesions.

Effects of pre-extraction intermittent PTH administration on extraction socket healing in bisphosphonate administered ovariectomized rats.

The purpose of this study was to investigate the effect of administering intermittent parathyroid hormone (iPTH) before tooth extraction versus after tooth extraction on the risk of developing MRONJ in experimental animal model. Twenty-five ovariectomized rats received 6 weeks of bisphosphonate therapy. They were classified into 3 groups, based on the timing of the medication, as Control, Pre-PTH and Post-PTH groups. For Control group, normal saline was administered before and after tooth extraction. iPTH was administered during 4 weeks before tooth extraction for Pre-PTH group and after tooth extraction for Post-PTH group. The animals were euthanized 8 weeks after tooth extraction. Macroscopic, histological, micro-computed tomography (micro-CT), and histomorphometric examinations were conducted. The incidences of impaired healing were 11.11% both in Pre-PTH and Post-PTH groups, which was lower than the Control group (42.86%). Bone healing in the extraction socket, based on micro-CT and histomorphometry evaluations, was best in Post-PTH and worst in Control group. The Pre-PTH group showed moderate healing pattern. Despite of limitations in this study, the authors identified Pre-PTH group seems to have positive effect on extraction socket healing. With regard to timing, administering iPTH after tooth extraction was superior to applying it before tooth extraction.

Open-Healing Socket Preservation with a Novel Dense Polytetrafluoroethylene (dPTFE) Membrane: A Retrospective Clinical Study.

Background and objectives: Non-resorbable dense polytetrafluoroethylene (dPTFE) membranes are widely used for regeneration procedures, alone or in combination with particulate materials. The aim of this work was to examine the efficacy of a newly developed dPTFE membrane in the management of extraction socket healing. Materials and Methods: The extraction premolar sockets of 44 patients (20 men and 24 women) were preserved. One group received prosthetic rehabilitation with a fixed partial denture (FPD) (PROS group, N = 19) and a second group received immediate implant placement (IMPL group, N = 25). The PROS group sockets were augmented with a bovine derived xenograft and covered with a newly developed dPTFE membrane prior to FPD rehabilitation. Results: In the IMPL group, socket preservation was combined with immediate implant placement. Before (T0) and 6 months after surgery (T1), horizontal and vertical dimensions were measured with customized stents. No significant differences in alveolar bone loss from T0 to T1 were observed between the PROS and IMPL groups in the horizontal dimension for any tooth type. There was a significant difference in alveolar bone loss from T0 to T1 between the two groups for only single-rooted maxillary premolars in the vertical dimension. Conclusions: The use of the examined new dPTFE membrane consistently led to the preservation of hard tissue in the extraction sites.

The effects of intro-oral parathyroid hormone on the healing of tooth extraction socket: an experimental study on hyperglycemic rats.

Objective To investigate the effects of intro-oral injection of parathyroid hormone (PTH) on tooth extraction wound healing in hyperglycemic rats. Methodology 60 male Sprague-Dawley rats were randomly divided into the normal group (n=30) and DM group (n=30). Type 1 diabetes mellitus (DM) was induced by streptozotocin. After extracting the left first molar of all rats, each group was further divided into 3 subgroups (n=10 per subgroup), receiving the administration of intermittent PTH, continuous PTH and saline (control), respectively. The intermittent-PTH group received intra-oral injection of PTH three times per week for two weeks. A thermosensitive controlled-release hydrogel was synthesized for continuous-PTH administration. The serum chemistry was determined to evaluate the systemic condition. All animals were sacrificed after 14 days. Micro-computed tomography (Micro-CT) and histological analyses were used to evaluate the healing of extraction sockets. Results The level of serum glucose in the DM groups was significantly higher than that in the non-DM groups (p<0.05); the level of serum calcium was similar in all groups (p>0.05). Micro-CT analysis showed that the DM group had a significantly lower alveolar bone trabecular number (Tb.N) and higher trabecular separation (Tb.Sp) than the normal group (p<0.05). The histological analyses showed that no significant difference in the amount of new bone (hard tissue) formation was found between the PTH and non-PTH groups (p>0.05). Conclusions Bone formation in the extraction socket of the type 1 diabetic rats was reduced. PTH did not improve the healing of hard and soft tissues. The different PTH administration regimes (continuous vs. intermittent) had similar effect on tissue healing. These results demonstrated that the metabolic characteristics of the hyperglycemic rats produced a condition that was unable to respond to PTH treatment.

Carbon nanotubes functionalized with sodium hyaluronate: Sterilization, osteogenic capacity and renal function analysis.

AIM: This study determined the optimum gamma irradiation dosage to sterilize sodium hyaluronate (HY), single-walled carbon nanotubes (SWCNT), multi-walled carbon nanotubes (MWCNT) and CNT functionalized with HY (HY-SWCNT and HY-MWCNT), evaluated the structural integrity of the materials and assessed whether sterilized materials kept biological properties without affecting renal function. MAIN METHODS: Materials were submitted to dosages of 100 gγ to 30 Kgγ and plated onto agar mediums for colony forming units (CFUs) counting. Sterilized samples were inoculated with 107Bacillus clausii, submitted again to gamma irradiation, and plated in agar mediums for CFUs counting. Scanning electron microscope was used for structural evaluation of sterilized materials. Tooth sockets of rats were treated with sterilized materials for bone formation assessment and renal function of the animals was analyzed. KEY FINDINGS: The optimum gamma dosage for sterilization was 250 gγ for HY and 2.5 Kgγ for the other materials without meaningful structural changes. Sterilized materials significantly increased bone formation (p < 0.05) and they did not compromise renal function and structure. SIGNIFICANCE: Gamma irradiation efficiently sterilized HY, SWCNT, MWCNT, HY-SWCNT and HY-MWCNT without affecting structural aspects while maintaining their desirable biological properties.

Effects of resveratrol on bone-healing capacity in the mouse tooth extraction socket.

BACKGROUND AND OBJECTIVE: After tooth extraction, the extraction socket undergoes several steps of soft and hard tissue healing. The healing process of the extraction socket is modulated by a range of signaling factors and biochemical agents. It has been reported that resveratrol, a polyphenolic compound, exhibits various biological effects, including anti-inflammatory, anti-carcinogenic, antioxidant, and anti-aging effects, and protects cardiovascular and bone tissues. In this study, we examined the cellular effects of resveratrol on human periodontal ligament (hPDL) cells and osteoblast-like (MC3T3-E1) cells and evaluated the bone-healing capacity of tooth extraction sockets in mice. MATERIAL AND METHODS: Resveratrol was applied to hPDL and MC3T3-E1 cells to detect cell proliferation and alkaline phosphatase (ALP) activity, and qPCR was employed to understand the gene expression level in vitro. For in vivo experiment, six-week-old C57BL/6 male mice were randomly divided into control (n = 15) and experimental (n = 15) groups and maxillary first molars were extracted by surgery. Experimental groups received 50-µM resveratrol on extraction sockets and analyzed the degree of new bone formation. RESULTS: Treatment of hPDL and MC3T3-E1 cells with resveratrol increased the cell proliferation and ALP activity and enhanced the expression of ALP, BMP-2, BMP-4, and OC genes. Resveratrol enhanced new bone formation in the lingual extraction socket in mice. CONCLUSION: These results suggest that resveratrol increases the cellular physiology of PDL and osteoblast including their proliferation and differentiation and may play an important role in bone-healing capacity after tooth extraction.

The effects of intro-oral parathyroid hormone on the healing of tooth extraction socket: an experimental study on hyperglycemic rats

Abstract Objective To investigate the effects of intro-oral injection of parathyroid hormone (PTH) on tooth extraction wound healing in hyperglycemic rats. Methodology 60 male Sprague-Dawley rats were randomly divided into the normal group (n=30) and DM group (n=30). Type 1 diabetes mellitus (DM) was induced by streptozotocin. After extracting the left first molar of all rats, each group was further divided into 3 subgroups (n=10 per subgroup), receiving the administration of intermittent PTH, continuous PTH and saline (control), respectively. The intermittent-PTH group received intra-oral injection of PTH three times per week for two weeks. A thermosensitive controlled-release hydrogel was synthesized for continuous-PTH administration. The serum chemistry was determined to evaluate the systemic condition. All animals were sacrificed after 14 days. Micro-computed tomography (Micro-CT) and histological analyses were used to evaluate the healing of extraction sockets. Results The level of serum glucose in the DM groups was significantly higher than that in the non-DM groups (p<0.05); the level of serum calcium was similar in all groups (p>0.05). Micro-CT analysis showed that the DM group had a significantly lower alveolar bone trabecular number (Tb.N) and higher trabecular separation (Tb.Sp) than the normal group (p<0.05). The histological analyses showed that no significant difference in the amount of new bone (hard tissue) formation was found between the PTH and non-PTH groups (p>0.05). Conclusions Bone formation in the extraction socket of the type 1 diabetic rats was reduced. PTH did not improve the healing of hard and soft tissues. The different PTH administration regimes (continuous vs. intermittent) had similar effect on tissue healing. These results demonstrated that the metabolic characteristics of the hyperglycemic rats produced a condition that was unable to respond to PTH treatment.

Evaluation of the effect of honey on the healing of tooth extraction wounds in 4- to 9-year-old children.

OBJECTIVE: The aim of the this study was to evaluate the effect of honey on the healing of tooth extraction wounds in children 4‒9 years of age. SUBJECTS AND METHODS: In the present randomized clinical trial, 51 patients, 4‒9 years of age were selected randomly. All the subjects required extraction of one deciduous molar tooth. The subjects were randomly assigned to two groups. In group 1, after extraction of the tooth, the dentist used a cotton swab applicator to place a layer of honey on a piece of gauze moistened with normal saline solution (NSS) and placed it on the socket. In group 2, honey was not used; rather, NSS was applied. On days 3 and 7 after tooth extraction, the wound sizes were measured. RESULTS: In both groups, the wound sizes decreased significantly on the third day compared with baseline and on the seventh day compared with the third day (P < 0.05). On the third and seventh days after tooth extraction, wound sizes in the honey group were significantly lower than those in the NSS group (P < 0.05). CONCLUSION: Honey resulted in a decrease in wound sizes and faster healing after extraction of teeth in children. Therefore, use of honey can be recommended after minor surgeries in the oral cavity.

The effects of luteolin nanoparticles on the healing of extracted tooth socket in rabbits

Objective: To evaluate the effects of luteolin nanoparticles on the process tooth socket healing in rabbits. Design: This study comprised five rabbits randomly assigned to control animal and experimental animals. Immediately after the extraction of an upper maxillary incisor, the alveolar sockets of experimental animals were treated with topical luteolin while alveolar sockets of the control group remained without treatment. The animals were sacrificed by decapitation with deep anesthesia seven days post tooth extraction. The tooth sockets were sectioned and stained with hematoxylin and eosin stains. Results: Histological evaluation revealed that luteolin treatment induced earlier healing of extracted tooth sockets. Conclusion: These findings suggest that luteolin accelerates the healing process in tooth sockets of rabbits.

WNT3A accelerates delayed alveolar bone repair in ovariectomized mice.

Our goal was to evaluate alveolar bone healing in OVX mice, and to assess the functional utility of a WNT-based treatment to accelerate healing in mice with an osteoporotic-like bony phenotype. INTRODUCTION: Is osteoporosis a risk factor for dental procedures? This relatively simple question is exceedingly difficult to answer in a clinical setting, for two reasons. First, as an age-related disease, osteoporosis is frequently accompanied by age-related co-morbidities that can contribute to slower tissue repair. Second, the intervals at which alveolar bone repair are assessed in a clinical study are often measured in months to years. This study aimed to evaluate alveolar bone repair in ovariectomized (OVX) mice and provide preclinical evidence to support a WNT-based treatment to accelerate alveolar bone formation. METHODS: OVX was performed in young mice to produce an osteoporotic-like bone phenotype. Thereafter, the rate of extraction socket healing and osteotomy repair was assessed. A liposomal WNT3A treatment was tested for its ability to promote alveolar bone formation in this OVX-induced model of bone loss. RESULTS: Bone loss was observed throughout the murine skeleton, including the maxilla, and mirrored the pattern of bone loss observed in aged mice. Injuries to the alveolar bone, including tooth extraction and osteotomy site preparation, both healed significantly slower than the same injuries produced in young controls. Given sufficient time, however, all injuries eventually healed. In OVX mice, osteotomies healed significantly faster if they were treated with L-WNT3A. CONCLUSIONS: Alveolar bone injuries heal slower in OVX mice that exhibit an osteoporotic-like phenotype. The rate of alveolar bone repair in OVX mice can be significantly promoted with local delivery of L-WNT3A.

Nerve electrical stimulation enhances osseointegration of implants in the beagle.

Dental implantation has been the primary method for the treatment of tooth loss, but longer than 3 months healing times are generally required. Because immediate load implants are suitable only for certain categories of implant patients, it has value to develop a novel method to facilitate the implant-bone osseointegration process. Cylindrical titanium implants were implanted in the tooth sockets of beagles, and microelectrode stimulation of the sympathetic nerves in the infraorbital nerve was performed after implantation for 1 week. The authors found that one-sided nerve stimulation was shown to evoke consistent electric potential changes in both sides of the infraorbital nerves. Moreover, after 4 weeks of implantation, more new bone was clearly observed around the implants in the beagles that received electrical stimulation treatment than was observed in the control animals. Furthermore, a higher mineralization density was measured in the new peri-implant bone tissues of the stimulated beagles when compared to controls. These results demonstrate that the simple and safe physical method of microelectrode stimulation to sympathetic nerves can promote the formation of new bone and the osseointegration of implants. This technique is worth promoting and has the potential to reduce the healing time of dental implantation in future clinical cases.

Prevention of tooth extraction-triggered bisphosphonate-related osteonecrosis of the jaws with basic fibroblast growth factor: An experimental study in rats.

Osteonecrosis of the jaw induced by administration of bisphosphonates (BPs), BP-related osteonecrosis (BRONJ), typically develops after tooth extraction and is medically challenging. As BPs inhibit oral mucosal cell growth, we hypothesized that suppression of the wound healing-inhibiting effects could prevent BRONJ onset after tooth extraction. Since basic fibroblast growth factor (bFGF) promotes wound healing, but has a short half-life, we examined whether the initiation of BRONJ could be prevented by applying a bFGF-containing gelatin hydrogel over the extraction sockets of BRONJ model rats. Forty-three rats, received two intravenous injections of zoledronic acid 60 µg/kg, once per week for a period of 2 weeks, underwent extraction of a unilateral lower first molar. The rats here were randomly assigned to the bFGF group (n = 15 rats, gelatin hydrogel sheets with incorporated bFGF applied over the sockets); the phosphate-buffered saline (PBS) group (n = 14 rats, gelatin hydrogel sheets without bFGF applied over the sockets); or the control group (n = 14 rats, nothing applied over the sockets). One rat in the bFGF group was sacrificed immediately after tooth extraction. Twenty-one rats were sacrificed at 3 weeks, and the remaining 21 rats were sacrificed at 8 weeks after tooth extractions. The harvested mandibles were analyzed using micro-computed tomography and sections were evaluated qualitatively for mucosal disruption and osteonecrosis. The incidence of osteonecrosis at 8 weeks after tooth extraction was 0% in the bFGF group, 100% in the PBS group, and 85.7% in the control group. The frequency of complete coverage of the extraction socket by mucosal tissue was significantly greater in the bFGF group than in the other groups. These results suggest that application of bFGF in the extraction socket promoted socket healing, which prevented BRONJ development. The growth-stimulating effects of bFGF may have offset the inhibition of wound healing by BP.

Effect of CBX7 deficiency on the socket healing after tooth extractions.

CBX7 is shown to down-regulate the expression of osteopontin (OPN) that is associated with osteoblast function. Here, we studied the role of CBX7 in the wound healing of tooth extraction socket in which osteoblast activity is critical via comparison between CBX7-knockout (CBX7-/-) mice and their wild-type (WT) counterparts of 6 weeks old with maxillary first molar extracted. Mice were euthanized at 7, 14, and 21 days after extractions, and alveolar sockets were assessed by semi-quantitative histomorphometry for hard tissue healing, including new bone fill (Masson's trichrome staining), osteoblast activity (OPN/osterix, Osx), osteoclast activity (tartrate-resistant acid phosphatase, TRAP), and for soft tissue healing, including blood vessels (alpha smooth muscle actin, α-SMA). Also, the bone microarchitecture was evaluated by micro-CT. In radiological analysis, CBX7-/- mice increased bone mass significantly more than WT mice did. Consistently, both the amount of new bone fill and OPN/Osx-immunopositive cells in the extraction sockets were significantly increased in CBX7-/- mice at each time point with respect to their WT siblings, while osteoclast number exhibited a trend of more increase in CBX7-/- mice at all time points as well. In agreement with enhanced bone formation during socket healing, significantly elevated α-SMA-immunopositive area was noted in CBX7-/- mice in contrast to WT mice. Taken together, these data suggest that CBX7 deficiency has a positive effect on tooth extraction socket healing.

Alendronate improves bone density and type I collagen accumulation but increases the amount of pentosidine in the healing dental alveolus of ovariectomized rabbits.

BACKGROUND: It has been shown that the oral aminobisphosphonate sodium alendronate (ALN) therapy reduces the risk of main fractures in osteoporotic women, but its effect on the jaw bones is poorly known. Here, we hypothesized that ALN affects the newly formed alveolar bone, particularly the quality of the type I collagen cross-linking. METHODS: Osteoporosis was induced by ovariectomy (OVX) in 6-month old rabbits. Six weeks following surgery, eight animals were treated by oral gavage with ALN (OVX + ALN) and ten received placebo (OVX + Pbo). Another six rabbits which were sham operated also received placebo (SHAM + Pbo). One month following the beginning of treatment, the upper and lower left first premolars were removed. Six weeks later, the upper and the lower right first premolars were also extracted. One month after the second extraction, biopsies were collected from the maxillary extraction sites and collagen crosslinks were analyzed in the newly formed bone tissue by HPLC. Also, at this time, mandibular bone segments were subjected to µCT. RESULTS: Animals treated with ALN achieved a roughly 2-time greater bone volume fraction value at a late healing period than animals in the other groups (p < 0.05). Collagen mean results were 2- to 4-times superior in the OVX + ALN group than in the control groups (p < 0.05). ALN-treated animals presented higher amounts of the non-enzymatic collagen cross-link pentosidine (PEN) than the sham-operated rabbits (p < 0.05), whereas the OVX + Pbo group presented the highest amount of PEN (p < 0.05). CONCLUSION: Alendronate increases bone volume and collagen accumulation, but does not fully rescue the non-osteoporotic alveolar tissue quality as is evident from the increased quantity of pentosidine.

Hyaluronic acid accelerates bone repair in human dental sockets: a randomized triple-blind clinical trial.

This study evaluated the effects of hyaluronic acid (HA) on bone repair of human dental sockets. Thirty-two lower first premolars were extracted from 16 patients (2 per patient) for orthodontic reasons. Following the extractions, one socket was randomly filled with 1% HA gel, while the other was allowed to naturally fill with blood clot. After 30 and 90 days of surgery, patients underwent cone beam computed tomography. Five central orthoradial slices were captured from each socket. The gray intensity was measured in each image and results were reported as mean percentage of bone formation. The buccolingual alveolar ridge width was measured and dimensional changes were compared between the postoperative intervals. The pattern of alveolar trabecular bone was evaluated through the fractal dimension. Treated sockets showed a higher percentage of bone formation and fractal dimension values (58.17% and 1.098, respectively) compared with controls (48.97% and 1.074, respectively) in the 30-day postoperative period (p < 0.05). After 90 days, there was no significant difference between groups. Additionally, no significant difference was found between groups regarding the alveolar dimensions (p > 0.05). Use of 1% HA gel after tooth extraction accelerates bone repair in human dental sockets.