Tooth Extraction Wound Healing Research Articles

Differential effects of clopidogrel and/or aspirin on the healing of tooth extraction wound bone tissue.

A multitude of variables influence the healing of tooth extraction wounds, and delayed or non-healing extraction wounds might complicate later prosthodontic therapy. In this research, we analyzed the effects of systemic clopidogrel and aspirin alone or in combination on the healing of tooth extraction wounds in mice in order to provide experimental evidence for the healing of extraction wounds in patients who are clinically treated with the two medicines. 7-week-old ICR mice were randomly divided into four groups: control group (CON), clopidogrel group (CLOP), aspirin group (ASP), and clopidogrel combined with aspirin group (CLOP + ASP); left upper first molar was extracted, after which mice in 1week of adaptive feeding, CLOP/ASP/CLOP + ASP groups were respectively administered with clopidogrel (10mg/kg/d), aspirin (15mg/kg/d), clopidogrel (10mg/kg/d)+aspirin (15mg/kg/d), and the control group was given an equal amount of 0.9% saline by gavage. Mice in each group were euthanized at 14 and 28days postoperatively, and the maxilla was extracted. The tissues in the extraction sockets were examined using MicroCT and sectioned for HE staining, Masson staining, and TRAP staining, and immunohistochemistry staining (for TRAP, RANKL and osteoprotegerin). MicroCT analysis showed that at day 14, BS/BV was significantly lower in CLOP and CLOP + ASP groups compared to control and ASP groups, while BV/TV, Tb.Th was significantly higher. At day 28, BV/TV was significantly higher in the CLOP + ASP group compared to the CLOP group, with p < 0.05 for all results. HE staining and Masson trichrome staining findings revealed that at day 28, the mesenchyme in the bone was further decreased compared to that at day 14, accompanied with tightly arranged and interconnected bone trabeculae. In the quantitative analysis of Masson, the fraction of newly formed collagen was significantly higher in the CLOP group in comparison with that in the CON group (p < 0.05). At day 14, the ASP group had substantially more TRAP-positive cells than the CLOP and CLOP + ASP groups (p < 0.05). In immunohistochemical staining, RANKL expression was found to be significantly higher in the ASP group than those in the other three groups at day 28 (p < 0.05); OPG expression was significantly higher in the CLOP group and the CLOP + ASP group compared with that at day 14, and was higher than that in the ASP group at day 14 and day 28. OPG/RANKL was significantly higher in the CLOP and the CLOP + ASP groups than in the ASP group (p < 0.05). Clopidogrel alone promotes osteogenesis in the extraction wound, whereas aspirin alone inhibits alveolar bone healing. When the two drugs were combined, the healing effect of the extraction wound was more similar to that of the clopidogrel alone group. These results indicated that clopidogrel could promote the healing of the tooth extraction wound, and neutralize the adverse effect of ASP on osteogenesis when the two drugs were used in combination.

Reversibly Adhesive, Anti-Swelling, and Antibacterial Hydrogels for Tooth-Extraction Wound Healing.

Oral wound treatment faces challenges due to the complex oral environment, thus, sealing the wound quickly becomes necessary. Although some materials have achieved adhesion and sterilization, how to effectively solve the contradiction between strong adhesion and on-demand removal remains a challenge. Herein, a reversibly adhesive hydrogel is designed by free radical copolymerization of cationic monomer [2-(acryloyloxy) ethyl] trimethylammonium chloride (ATAC), hydrophobic monomer ethylene glycol phenyl ether acrylate (PEA) and N-isopropylacrylamide (NIPAAm). The cationic quaternary ammonium salts provide electrostatic interactions, the hydrophobic groups provide hydrophobic interactions, and the PNIPAAm chain segments provide hydrogen bonding, leading to strong adhesion. Therefore, the hydrogel obtains an adhesion strength of 18.67KPa to oral mucosa and can seal wounds fast within 10s. Furthermore, unlike pure PNIPAAm, the hydrogel has a lower critical solution temperature of 40.3°C due to the contribution of ATAC and PEA, enabling rapid removal with 40°C water after treatment. In addition, the hydrogel realizes excellent anti-swelling ratio (≈80%) and antibacterial efficiency (over 90%). Animal experiments prove that the hydrogel effectively reduces inflammation infiltration, promotes collagen deposition and vascular regeneration. Thus, hydrogel as a multi-functional dressing has great application prospects in oral wound management.

Effectiveness of Snakehead Fish Extract on Tooth Extraction Wound Healing

Tooth extraction can cause open wound in the oral cavity, if not handled properly it can cause complications such as bleeding, infection and delayed wound healing. Wound healing is a biological process associated with tissue growth and regeneration. The wound healing process can be accelerated by administering chemicals that can affect the inflammatory, proliferative and remodeling phases. One of them is by giving snakehead fish extract. The extract contains albumin, copper and zinc which play an important role in the wound healing phase. The purpose of writing this review article is to explain the mechanism of snakehead fish extract in accelerating the healing of tooth extraction wounds. Several studies have revealed that snakehead fish extract affects pro-inflammatory cytokines in helping the wound healing process and significantly helps increase the number of fibroblast cells in tooth socket wounds, so that the healing process can take place more quickly. Based on this, it can be concluded that snakehead fish extract has the potential to accelerate the healing of tooth extraction wounds.

To evaluate the effects of Low-level laser therapy (LLLT) on wound healing of extraction socket: A systematic review

Background: Low power laser therapy or low-level laser therapy (LLLT) is relatively novel and has demonstrated tremendous advantages in dentistry which includes reduction in post-surgical pain as well as swelling and also accelerates wound healing and helps in bone regeneration etc. Objective: This systematic review aimed to find out whether low-level laser therapy promotes tooth extraction wound healing. Materials and Methods: Literature was searched from January 2010 till 31 December 2020 using PubMed, Scopus, and Web of science. Further findings were done from gray literature google scholar, and Research Gate using Low-level laser therapy, photobiomodulation, wound healing, extraction socket healing, cold laser, biostimulation, low-level laser irradiation, and phototherapy. Any article that reported effects of low-level laser therapy on wound healing was included. 19 studies fulfilled the criteria and were included for this systematic review. Quality assessment was done for each article using Joanna Briggs Institute (JBI) checklist for analytical cross-sectional studies. Results and Discussion: Throughout the search, approximately 22,808 relevant articles were found. Out of which 50 articles fulfilled the selection criteria. 31 articles were excluded because that did not fulfill inclusion criteria. 19 articles were included for this systematic review that compared the effects of low level-laser therapy on wound healing after extraction of a tooth. Conclusion: Overall, this systematic review concluded that low-level laser therapy enhanced the process of wound healing after extraction of teeth but most of the research was conducted on animals. Further research is needed to investigate the biostimulatory effects of low-level irradiation on wound healing after extraction of a tooth Bangladesh Journal of Medical Science Vol. 22 No. 03 July’23 Page : 585-597

The evaluation of the effects of natural zeolite (Clinoptilolite) in diabetic rats on bone healing in dental extracting socket.

The fact that clinoptilolite reserves are abundant and economical in the world, its toxic effects are not observed in clinical studies in humans and animals, and it has superior physical properties suggests that clinoptilolite may be an easily accessible product for the healing of tooth extraction wounds. The aim of the study was to evaluate the effects of cliniotilolite on bone tissue healing and bone formation in the extraction socket in experimentally diabetic rats by micro-CT analysis. 36 male Wistar Albino rats were divided into 3 main groups as Healthy Control, Diabetes Control and Diabetes+Clinoptilolite. Afterwards, these groups were divided into 2 subgroups to be sacrificed on the 14th and 28th days, and each subgroup had 6 rats (n=6). At the 14th and 28th days, the rats were sacrificed and the effects of clinoptilolite on bone tissue healing and bone formation in the alveolar socket were evaluated by micro-CT analysis. According to the statistical analysis results, the difference between the groups in terms of bone volume, bone surface to bone volume, trabecular thickness and hounsfield units values, which are the parameters of the 14th day groups, was statistically significant (p<0.05). Among the parameters of the 28th day groups, only the hounsfield units value was statistically significant (p<0.05). The results of the study show that clinoptilolite can contribute to the healing of extraction wounds and bone formation.

Fluorescent risedronate analogue 800CW-pRIS improves tooth extraction-associated abnormal wound healing in zoledronate-treated mice

BackgroundBisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but serious side effect of nitrogen-containing bisphosphonate drugs (N-BPs) frequently prescribed to reduce skeletal-related events in bone malignancies and osteoporosis. BRONJ is associated with abnormal oral wound healing after dentoalveolar surgery and tooth extraction. We previously found that N-BP chemisorbed to bone mineral hydroxyapatite was dissociated by secondary applied N-BP. This study investigated the effect of the surface equilibrium-based removal of N-BP from jawbone on tooth extraction wound healing of zoledronate (ZOL)-treated mice.MethodsA pharmacologically inactive N-BP derivative (the 4-pyridyl isomer of risedronate equipped with a near-infrared 800CW fluorescent imaging dye, 800CW-pRIS) was designed and synthesized. 800CW-pRIS was intra-orally injected or topically applied in a deformable nano-scale vesicle formulation (DNV) to the palatal tissue of mice pretreated with ZOL, a potent N-BP. The female C56BL6/J mice were subjected to maxillary molar extraction and oral wound healing was compared for 800CW-pRIS/ZOL, ZOL and untreated control groups.Results800CW-pRIS is confirmed to be inactive in inhibiting prenylation in cultured osteoclasts while retaining high affinity for hydroxyapatite. ZOL-injected mice exhibit delayed tooth extraction wound healing with osteonecrosis relative to the untreated controls. 800CW-pRIS applied topically to the jaw one week before tooth extraction significantly reduces gingival oral barrier inflammation, improves extraction socket bone regeneration, and prevents development of osteonecrosis in ZOL-injected mice.ConclusionsTopical pre-treatment with 800CW-RIS in DNV is a promising approach to prevent the complication of abnormal oral wound healing associated with BRONJ while retaining the anti-resorptive benefit of legacy N-BP in appendicular or vertebrate bones.

High‐Strength and Injectable Supramolecular Hydrogel Self‐Assembled by Monomeric Nucleoside for Tooth‐Extraction Wound Healing (Adv. Mater. 13/2022)

Supramolecular Hydrogels In article number 2108300, Hang Zhao, Xianglong Han, Qianming Chen, and co-workers introduce a high-strength and injectable supramolecular hydrogel, which was constructed by the self-assembly of a monomeric nucleoside molecular gelator (2-amino-2'-fluoro-2'-deoxyadenosine, 2-FA). Notably, it also exhibits excellent biocompatibility, fast biodegradation, antibacterial properties, and osteoclast inhibition, making it a potential candidate biomaterial for tooth-extraction wound healing and tissue engineering.

Topical Medicine Potency of Musa paradisiaca var. sapientum (L.) kuntze as Oral Gel for Wound Healing: An In Vitro, In Vivo Study.

Topical application of ambonese banana (Musa paradisiaca var. sapientum (L.) kuntze) stem sap gel (GEGPA) on the socket wound area showed an increase in the expression of platelet-derived growth factor-BB, while decrease in the expression of matrix metalloproteinase-2 and 9. The aim of this study is to achieve standard formulation of GEGPA through stability, viscosity, distribution area, and drugs release for oral gel wound healing. This is an in vitro and in vivo study with the randomized posttest only control group design. The gel was formulated according to the composition of each group by adding hydroxypropyl methylcellulose (HPMC), Lexgard, propylene glycol, and cold water to obtain 100 g of gel. Observations were made through the following tests: stability, viscosity, distribution area, drug release, and histopathological analysis of tooth extraction wound healing. Data were analyzed using a one-way analysis of variance (α = 0.05) with GraphPad Prism-8 statistical software. The study showed that the GEGPA formulation was stable against changes in consistency, color, smell, homogeneity, and pH value. There is a significant difference between groups with respect to viscosity (p = 0.0001), adhesion (p = 0.004), dispersion (p = 0.000), and fibroblast cell numbers on days 3 and 5 (p = 0.007 and p = 0.001). There is no interaction between the active ingredients and the gel base of all formulations. Formulation 3 had better properties in terms of viscosity, broad distribution, and drug release compared with other groups. Application of GEGPA to tooth extraction wounds showed a significant proliferation of fibroblast cells on days 3 and 5. The formulation of M. paradisiaca var. sapientum (L.) kuntze extract with HPMC and propylene glycol obtained a gel preparation, GEGPA, that was organoleptically stable and met the topical gel standard for wounds in the oral cavity.

An in-vivo study of photobiomodulation using 403\xa0nm and 649\xa0nm diode lasers for molar tooth extraction wound healing in wistar rats

PurposeThis study aims to examine the effects of red 649 nm 4 J/cm2 and blue 403 nm 8 J/cm2 diode laser treatment for post-extraction wounded healing in rats through histopathological and immunohistochemical analysis.MethodsSamples of 54 Wistar rats were divided into six groups: C- control group without treatment; C + wounded group without treatment; TB wound group with Povidone-iodine treatment; TD wounded group with doxycycline treatment; TLB wounded group with 403 nm diode laser treatment; and TLR wounded group with 649 nm diode laser treatment. Mandibular samples were observed for the number of lymphocytes and fibroblasts cells, new blood vessels formation, Interleukin 1β, and Collagen 1α expression level.ResultsBased on the histopathological test results, red laser diode treatment significantly increased the number of lymphocyte, fibroblast cells and the formation of new blood vessels. Meanwhile, immunohistochemical tests showed an increase in the expression of the Colagen-1α protein which plays a role in the formation of collagen for new tissues formation after damage, as well as a decrease in Interleukin-1β expression level. Blue laser is also able to show a positive effect on wound healing even though its penetration level into the tissue is lower compared to red laser.ConclusionThe red diode laser 649 nm has been shown to accelerate the process of proliferation in wound healing post molar extraction based on histopathological and immunohistochemical test results.

Effect of bisphosphonates on healing of tooth extraction wounds in infectious osteomyelitis of the jaw.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) and infectious osteomyelitis of the jaw (OMJ) in antiresorptive-naïve patients are different disease entities. Although osteoclast inhibition is at the center of the pathogenesis of ARONJ, the role of osteoclast inhibition in infectious OMJ is unknown. The objective of this study was to determine the effect of bisphosphonate osteoclast inhibition in infectious OMJ. Osteomyelitis was induced in mice by S. aureus inoculation. The establishment of OMJ was verified by the culture of bone marrow samples obtained from the mandible. Infected animals received either zoledronic acid (ZA) or saline starting at week-2. Treated animals along with non-infected animals underwent tooth extractions at week-4 post-infection. Healing was assessed every week using in vivo micro-computed tomography and intraoral photos. Animals were euthanized at week-8 and cervical lymph nodes were assessed for lymphatic and blood vessels. Tooth extraction wounds did not heal in animals with OMJ. These wounds were characterized by incomplete soft tissue coverage, sporadic bone fill in the sockets, and inflammatory cell accumulation in the connective tissue at 4weeks after tooth extractions. Conversely, the majority of tooth extraction wounds in the infected animals treated with ZA had improved healing with better bone fill than even non-infected control animals. Consistently, atrophic lymphatic vessels were noted in the draining lymph nodes in animals with OMJ. However, infected animals treated with ZA had lymphatic vessels that were unaltered and showed a similar appearance to those in non-infected control animals. ZA treatment promoted wound healing in the jaw with infectious osteomyelitis. Clearly, antiresorptive therapy is contraindicated in patients with ARONJ. However, our finding suggests that osteoclast inhibition is potentially an effectual remedy for infectious OMJ in antiresorptive-naïve patients.

Interspecies comparison of alveolar bone biology: Tooth extraction socket healing in mini pigs and mice.

in an effort to identify and validate which animal models are best suited for dental implant research, we used multiscale analyses to examine tooth extraction wound healing in a well-accepted model, the Yucatan mini pig and a more controversial model, the laboratory mouse. first molar extractions were performed in adult, skeletally mature mini pigs and mice. Alveolar bone repair was evaluated at early, intermediate and late timepoints using quantitative micro-computed tomographic (μCT) imaging, histology, molecular, and cellular assays. Vital dye labeling was employed to quantify mineral apposition rates (MAR) in both species. Despite a 3000-fold difference in weight, the relative proportions of the mini pig and murine maxillae and are equivalent. Quantitative μCT demonstrated that within the posterior alveolar bone, the volume of mineralized bone was lower in mini pig than in the mice; during healing, however, the bone volume fraction was equivalent. The histologic appearance of healing sites was also comparable, and alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP) staining showed a similar temporal and spatial distribution of bone remodeling. Vital dye labeling indicated equivalent MAR between the species. The absolute duration of the healing period differed: in mice, complete healing was accomplished in ∼21 days. In mini pigs, the same process took four times longer. Extraction socket healing is histologically equivalent between mini pigs and mice, supporting the hypothesis that the underlying mechanisms of alveolar bone healing are conserved among species.

Strontium ranelate improves alveolar bone healing in estrogen-deficient rats.

This study evaluated the impact of strontium ranelate on tooth-extraction wound healing in estrogen-deficient and estrogen-sufficient rats. Ninety-six Wistar rats (90 days of age) were allocated into one of the following groups: sham-surgery+water (estrogen-sufficient); ovariectomy+water (estrogen-deficient), sham-surgery+strontium ranelate (625mg/kg/d) (strontium/estrogen-sufficient); ovariectomy+strontium ranelate (625mg/kg/d) (strontium/estrogen-deficient). Water or strontium ranelate were administrated from the 14th day post-ovariectomy/sham surgery until euthanasia. Maxillary first molars were extracted at 21 days after sham/ovariectomy surgery. Rats were euthanized at 10, 20, and 30 days post-extractions. The following parameters were analyzed inside tooth-extraction wound: proportion of newly formed bone (bone healing/BH), number of cells stained for tartrate-resistant acid phosphatase (TRAP) and immunohistochemical staining for five bone metabolism-related markers (osteocalcin [OCN], osteopontin [OPN], bone sialoprotein [BSP], osteoprotegerin [OPG] and receptor activator of NF-КB ligand [RANKL]). The estrogen-deficient group presented lower BH than all other groups at 20 and 30 days post-extraction (P<0.05). The number of TRAP-stained cells was higher in the estrogen-deficient group than in estrogen-sufficient group at 30 days post-extraction (P<0.05). The strontium /estrogen-sufficient group exhibited stronger staining for OCN, when compared to the estrogen-sufficient and estrogen-deficient groups (P<0.05). Both strontium ranelate-treated groups presented higher staining of OPN and BSP than both untreated groups (P<0.05). The strontium/estrogen-sufficient group demonstrated stronger staining for OPG than the estrogen-deficient group (P<0.05). The estrogen-sufficient group and both groups treated with strontium ranelate showed lower expression of RANKL than the estrogen-deficient group (P<0.05). Strontium ranelate benefited BH and the expression of bone markers in tooth-extraction wound in estrogen-deficient rats whereas its benefits in estrogen-sufficient rats were modest.

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.

Rescue bisphosphonate treatment of alveolar bone improves extraction socket healing and reduces osteonecrosis in zoledronate-treated mice.

Bisphosphonate (BP)-related osteonecrosis of the jaw, previously known as BRONJ, now referred to more broadly as medication-related osteonecrosis of the jaw (MRONJ), is a morbid condition that represents a significant risk for oncology patients who have received high dose intravenous (IV) infusion of a potent nitrogen containing BP (N-BP) drug. At present, no clinical procedure is available to prevent or effectively treat MRONJ. Although the pathophysiological basis is not yet fully understood, legacy adsorbed N-BP in jawbone has been proposed to be associated with BRONJ by one or more mechanisms. We hypothesized that removal of the pre-adsorbed N-BP drug common to these pathological mechanisms from alveolar bone could be an effective preventative/therapeutic strategy. This study demonstrates that fluorescently labeled BP pre-adsorbed on the surface of murine maxillo-cranial bone in vivo can be displaced by subsequent application of other BPs. We previously described rodent BRONJ models involving the combination of N-BP treatment such as zoledronate (ZOL) and dental initiating factors such as tooth extraction. We further refined our mouse model by using gel food during the first 7 days of the tooth extraction wound healing period, which decreased confounding food pellet impaction problems in the open boney socket. This refined mouse model does not manifest BRONJ-like severe jawbone exposure, but development of osteonecrosis around the extraction socket and chronic gingival inflammation are clearly exhibited. In this study, we examined the effect of benign BP displacement of legacy N-BP on tooth extraction wound healing in the in vivo model. Systemic IV administration of a low potency BP (lpBP: defined as inactive at 100 μM in a standard protein anti-prenylation assay) did not significantly attenuate jawbone osteonecrosis. We then developed an intra-oral formulation of lpBP, which when injected into the gingiva adjacent to the tooth prior to extraction, dramatically reduced the osteocyte necrosis area. Furthermore, the tooth extraction wound healing pattern was normalized, as evidenced by timely closure of oral soft tissue without epithelial hyperplasia, significantly reduced gingival inflammation and increased new bone filling in the extraction socket. Our results are consistent with the hypothesis that local application of a rescue BP prior to dental surgery can decrease the amount of a legacy N-BP drug in proximate jawbone surfaces below the threshold that promotes osteocyte necrosis. This observation should provide a conceptual basis for a novel strategy to improve socket healing in patients treated with BPs while preserving therapeutic benefit from anti-resorptive N-BP drug in vertebral and appendicular bones.

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

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. 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. 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). 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.

Sponge amnion potential in post tooth extraction wound healing by interleukin-6 and bone morphogenetic protein-2 expression analysis: An animal study

Wound tooth extraction is a mechanical injury that traumatizes adjacent tissue. Sponge amnion contains growth factors that can promote postextraction wound healing. Amnion membranes can be transformed into sponge form rendering it easier to use. The aim of this study is to analyze interleukin-6 (IL-6) and bone morphogenetic protein-2 (BMP-2) expression in postextraction wound healing on the 1st and 7th day after sponge amnion application. Twenty-eight Wistar rats were used in this experimental descriptive analytical study. Fourteen animals' first right anterior mandible tooth was extracted; then, the socket applied by sponge amnion and sutured (treatment group), while 14 others only sutured (as control group). The alveolar bone tissue of animal was observed 1st and 7th days after extraction and then was analyzed using immunohistostaining to identify the expression of IL-6 and BMP-2. Statistical analysis was performed using one-way ANOVA with the level of significance (P < 0.05). IL-6 expression in the treatment group was significantly lower than the control group on the 1st and 7th days (P = 0.000). BMP-2 expression in the treatment group was significantly higher than the control group on the 1st and 7th days (P = 0.000). Sponge amnion can promote the healing process by increasing the expression of BMP-2 and decreasing IL-6 expression.

Risk of Delayed Healing of Tooth Extraction Wounds and Osteonecrosis of the Jaw among Patients Treated with Potential Immunosuppressive Drugs: A Retrospective Cohort Study.

Bone-modifying or antiresorptive agents that target osteoclasts, such as bisphosphonates, are known to cause delayed wound healing and osteonecrosis of the jaw (ONJ) following tooth extraction. However, there are no data on whether such adverse events are also caused by drugs that may suppress the immune system, including corticosteroids, immunosuppressants, biological agents, and disease-modifying anti-rheumatic drugs (DMARDs). The aim of this retrospective study was to examine the incidence of delayed post-extraction wound healing and identify risk factors among patients treated with potential immunosuppressive drugs undergoing tooth extraction. We performed a retrospective cohort study involving 101 patients by reviewing their medical records. The underlying diseases of the enrolled patients included dilated cardiomyopathy, hematological malignancy, sarcoidosis, rheumatoid arthritis, and systemic lupus erythematosus. The sample comprised 131 cases of tooth extraction among the 101 patients; delayed post-extraction wound healing occurred in 10 patients (12 cases, 9.2%), including ONJ in three patients (3 cases, 2.3%). The surgical tooth extraction performed for impacted teeth or a residual root (P = 0.009), the number of surgical tooth extraction (P = 0.012), decreased lymphocyte counts (P = 0.008), and decreased eosinophil counts (P = 0.009) were significantly related to delayed wound healing. Thus, among patients taking corticosteroids, immunosuppressants, biological agents, and/or DMARDs, there is a risk of delayed wound healing and ONJ. Moreover, the significant risk factors are low lymphocyte counts, low eosinophil counts, and surgical extraction. It is of particular importance to prevent surgical site infection, when the high-risk patients undergo tooth extraction.

Plasticity of Myeloid Cells during Oral Barrier Wound Healing and the Development of Bisphosphonate-related Osteonecrosis of the Jaw

Injury to the barrier tissue initiates a rapid distribution of myeloid immune cells from bone marrow, which guide sound wound healing. Bisphosphonates, a widely used anti-bone resorptive drug with minimal systemic side effects, have been linked to an abnormal wound healing in the oral barrier tissue leading to, in some cases, osteonecrosis of the jaw (ONJ). Here we report that the development of ONJ may involve abnormal phenotypic plasticity of Ly6G+/Gr1+ myeloid cells in the oral barrier tissue undergoing tooth extraction wound healing. A bolus intravenous zoledronate (ZOL) injection to female C57Bl/6 mice followed by maxillary first molar extraction resulted in the development of ONJ-like lesion during the second week of wound healing. The multiplex assay of dissociated oral barrier cells exhibited the secretion of cytokines and chemokines, which was significantly modulated in ZOL mice. Tooth extraction-induced distribution of Ly6G+/Gr1+ cells in the oral barrier tissue increased in ZOL mice at week 2. ONJ-like lesion in ZOL mice contained Ly6G+/Gr1+ cells with abnormal size and morphology as well as different flow cytometric staining intensity. When anti-Ly6G (Gr1) antibody was intraperitoneally injected for 5 days during the second week of tooth extraction, CD11b+GR1(hi) cells in bone marrow and Ly6G+ cells in the oral barrier tissue were depleted, and the development of ONJ-like lesion was significantly attenuated. This study suggests that local modulation of myeloid cell plasticity in the oral barrier tissue may provide the basis for pathogenesis and thus therapeutic as well as preventive strategy of ONJ.

Effect of Alendronate on Bone Formation during Tooth Extraction Wound Healing

Alendronate (ALN) is an antiresorptive agent widely used for the treatment of osteoporosis. Its suppressive effect on osteoclasts has been extensively studied. However, the effect of ALN on bone formation is not as clear as its effect on resorption. The objective was to determine the effect of short-term ALN on bone formation and tooth extraction wound healing. Molar tooth extractions were performed in mice. ALN, parathyroid hormone (PTH), or saline (vehicle control) was administered. PTH was used as the bone anabolic control. Mice were euthanized at 3, 5, 7, 10, and 21 d after extractions. Hard tissue healing was determined histomorphometrically. Neutrophils and lymphatic and blood vessels were quantified to evaluate soft tissue healing. Gene expression in the wounds was assessed at the RNA level. Furthermore, the vossicle bone transplant system was used to verify findings from extraction wound analysis. Alkaline phosphatase (ALP) was visualized in the vossicles to assess osteoblast activity. ALN exhibited no negative effect on bone formation. In intact tibiae, ALN increased bone mass significantly more than PTH did. Consistently, significantly elevated osteoblast numbers were noted. In the extraction sockets, bone fill in the ALN-treated mice was equivalent to the control. Genes associated with bone morphogenetic protein signaling, such as bmp2, nog, and dlx5, were activated in the extraction wounds of the ALN-treated animals. Bone formation in vossicles was significantly enhanced in the ALN versus PTH group. In agreement with this, ALN upregulated ALP activity considerably in vossicles. Neutrophil aggregation and suppressed lymphangiogenesis were evident in the soft tissue at 21 d after extraction, although gross healing of extraction wounds was uneventful. Bone formation was not impeded by short-term ALN treatment. Rather, short-term ALN treatment enhanced bone formation. ALN did not alter bone fill in extraction sockets.

RUNX2 expression during early healing of tooth-extraction wounds in rats

Determining the molecular mechanisms involved in the healing of wounds created by tooth extraction will likely increase understanding of jawbone healing after dental surgery. Runt-related transcription factor 2 (RUNX2) is required for mesenchymal stem cells to differentiate to osteoprogenitor cells. Therefore, we used a rat model to analyze RUNX2 expression during wound-socket healing after tooth extraction. Immunohistochemical analyses of wound tissue immediately after tooth extraction revealed RUNX2 expression in monocytic cells in the coagulum and, to a lesser extent, in remnants of the periodontal ligament. Shortly thereafter, fibroblastic cells proliferated in the coagulum and large polymorphic cells were enclosed within the newly formed bone matrix. Western blot analysis showed that RUNX2 expression peaked from 12 h to 1 day after extraction and then rapidly declined. These findings indicate that the osteogenic commitment of cells derived from hematopoietic tissue in the extraction wound was greater than that of cells in remnants of the periodontal ligament. Thus, cells derived mainly from hematopoietic tissue and RUNX2 expression are essential in the differentiation of mesenchymal stem cells to osteoprogenitor cells immediately after tooth extraction.