Use of autologous tooth-derived material as a graft in the post-extraction socket. Split-mouth study with radiological and histological analysis.

BACKGROUND: The healing process after tooth removal involves bone remodelling which implies some loss of alveolar bone volume. Among materials proposed for minimising this remodelling and preserving the bone, autologous dental tissue is a promising option, but more data are needed. In this context, we evaluated size and density changes using cone beam computed tomography in autologous dental material (ADM)-preserved sockets compared to controls, and assessed biological responses by histological analysis. METHODS: A split-mouth study was conducted including 22 patients, who underwent removal of ≥ 2 single-rooted teeth with intact sockets, assigning one socket to the experimental group which received ADM for alveolar preservation and another to the control group, which only underwent blood clot stabilisation. Cone beam computed tomography was performed postoperatively (week 0) and at weeks 8 and 16 to assess socket size and bone density. Histological analysis was carried out on trephine biopsies taken (Ø4 × 4.5 mm) from the experimental group. RESULTS: Less horizontal shrinkage was observed in the ADM group, especially at week 16 considering the group-by-time interaction for the following variables: difference in height between the lingual and buccal alveolar crests (-1.00; p < .01; 95% CI: -0.28 - -1.73), and half-widths, measured as the distance from the long axis of the missing tooth to the buccal alveolar crest at 1 mm (-0.61; p < .01; 95% CI: -0.18 - -1.04) and at 3 mm (-0.56; p < .01; 95% CI: -0.15 - -0.97) below the crest, with mean decreases of 1.07 and 2.14 mm in height difference, 0.66 and 1.32 mm in half-width at 1 mm and 0.43 and 1.02 mm in half-width at 3 mm in ADM and control groups respectively. Densitometry analysis showed higher bone densities in Hounsfield units in the ADM group considering all factors analysed regardless of time point and socket third (coronal, middle, or apical). Histologically, there were no signs of inflammation or foreign body reaction, and dentin particles were surrounded by and in close contact with bone tissue. CONCLUSION: These results add to the evidence that dentin can be used successfully as a material for alveolar socket preservation, given its desirable mechanical and biological properties, and warrant larger studies.

NF-κB Decoy Oligodeoxynucleotide-Loaded Poly Lactic-co-glycolic Acid Nanospheres Facilitate Socket Healing in Orthodontic Tooth Movement.

Orthodontic space closure following tooth extraction is often hindered by alveolar bone deficiency. This study investigates the therapeutic use of nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides loaded with polylactic-co-glycolic acid nanospheres (PLGA-NfDs) to mitigate alveolar bone loss during orthodontic tooth movement (OTM) following the bilateral extraction of maxillary first molars in a controlled experiment involving forty rats of OTM model with ethics approved. The decreased tendency of the OTM distance and inclination angle with increased bone volume and improved trabecular bone structure indicated minimized alveolar bone destruction. Reverse transcription-quantitative polymerase chain reaction and histomorphometric analysis demonstrated the suppression of inflammation and bone resorption by downregulating the expression of tartrate-resistant acid phosphatase, tumor necrosis factor-α, interleukin-1ß, cathepsin K, NF-κB p65, and receptor activator of NF-κB ligand while provoking periodontal regeneration by upregulating the expression of alkaline phosphatase, transforming growth factor-ß1, osteopontin, and fibroblast growth factor-2. Importantly, relative gene expression over the maxillary second molar compression side in proximity to the alveolus highlighted the pharmacological effect of intra-socket PLGA-NfD administration, as evidenced by elevated osteocalcin expression, indicative of enhanced osteocytogenesis. These findings emphasize that locally administered PLGA-NfD serves as an effective inflammatory suppressor and yields periodontal regenerative responses following tooth extraction.

Detection of senescent cells in the mucosal healing process on type 2 diabetic rats after tooth extraction for biomaterial development.

The delayed mucosal healing of tooth extraction sockets in diabetes has few known effective treatment strategies, and its underlying mechanism remains unknown. Senescent cells may play a pivotal role in this delay, given the well-established association between diabetes, senescent cells, and wound healing. Here, we demonstrated an increase in p21- or p16-positive senescent cells in the epithelial and connective tissues of extraction sockets in type 2 diabetic rats compared to those in control rats. Between 7 and 14 days after tooth extraction, a decrease in senescent cells and improvement in re-epithelialization failure were observed in the epithelium, while an increase in senescent cells and persistence of inflammation were observed in the connective tissue. These results suggest that cellular senescence may have been induced by diabetes and contributed to delayed mucosal healing by suppressing re-epithelization and persistent inflammation. These findings provide new targets for treatment using biomaterials, cells, and drugs.

Histological Evaluation of Alveolar Ridge Preservation Using Different Bone Grafts: Clinical Study Analysis Part II.

To compare histologically the percentage of bone formation 12-20 weeks after ridge augmentation using 2 different techniques. Tooth loss is associated with 3-dimensional bone remodeling and ridge atrophy. Ridge preservation procedures can prevent alveolar bone volume loss. Different techniques and materials are used to preserve the alveolar ridge. Computer-generated randomization software was used to assign 2 ridge preservation techniques for 11 extraction sites. In group I, type I bovine Achilles tendon collagen plugs with bioactive resorbable calcium apatite crystals (CPCAC) were placed, and in group II, cortico-cancellous bone chips (CCBC) mix and an expanded polytetrafluoroethylene (ePTFE) barrier membrane were placed. The histomorphometric studies were performed using a computer-based image analysis system (ImageJ 1.4, National Institute of Health, Bethesda, Md) to calculate the pixel area of bone tissue and the remaining bone graft material. The histomorphometric data were analyzed using a Student t test to compare the measurements between the 2 experimental groups. This parametric statistical test was employed to determine if there were any statistically significant differences in the quantitative histological parameters between the groups. The sockets that received CPCAC showed a lower (31.89%) percentage of native bone surface area compared with the CCBC group (43.87%). However, the difference was not statistically significant (P < .05). In addition, the CPCAC group showed evidence of foreign-body reaction. The CCBC graft covered with an ePTFE barrier may induce more bone formation with minimal inflammation in an extraction socket compared with a collagen plug with calcium apatite crystals. In addition, histological analysis of the CPCAC graft showed evidence of foreign-body reaction, which indicates a negative clinical impact.

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.

Regeneration of alveolar bone defects in the experimental pig model: A systematic review and meta-analysis.

OBJECTIVE: Pigs are emerging as a preferred experimental in vivo model for bone regeneration. The study objective was to answer the focused PEO question: in the pig model (P), what is the capacity of experimental alveolar bone defects (E) for spontaneous regeneration in terms of new bone formation (O)? METHODS: Following PRISMA guidelines, electronic databases were searched for studies reporting experimental bone defects or extraction socket healing in the maxillae or mandibles of pigs. The main inclusion criteria were the presence of a control group of untreated defects/sockets and the assessment of regeneration via 3D tomography [radiographic defect fill (RDF)] or 2D histomorphometry [new bone formation (NBF)]. Random effects meta-analyses were performed for the outcomes RDF and NBF. RESULTS: Overall, 45 studies were included reporting on alveolar bone defects or extraction sockets, most frequently in the mandibles of minipigs. Based on morphology, defects were broadly classified as 'box-defects' (BD) or 'cylinder-defects' (CD) with a wide range of healing times (10 days to 52 weeks). Meta-analyses revealed pooled estimates (with 95% confidence intervals) of 50% RDF (36.87%-63.15%) and 43.74% NBF (30.47%-57%) in BD, and 44% RDF (16.48%-71.61%) and 39.67% NBF (31.53%-47.81%) in CD, which were similar to estimates of socket-healing [48.74% RDF (40.35%-57.13%) and 38.73% NBF (28.57%-48.89%)]. Heterogeneity in the meta-analysis was high (I2 > 90%). CONCLUSION: A substantial body of literature revealed a high capacity for spontaneous regeneration in experimental alveolar bone defects of (mini)pigs, which should be considered in future studies of bone regeneration in this animal model.

Histologic wound healing in studies using different ridge preservation protocols: A review.

BACKGROUND: Alveolar ridge preservation (ARP) procedures are designed to lessen dimensional changes in the alveolar ridge after tooth extraction. Wound healing after ridge preservation involves the formation of new vital bone in the former socket, and this vital bone is important in the osseointegration of dental implants. METHODS: A series of ARP studies have been performed to help clinicians better understand the wound-healing events that occur following tooth extraction and ridge preservation. Different protocols have been examined using various materials and periods of healing time prior to implant placement. The primary aim of these studies was to ascertain the relative percentage of vital bone formation, residual graft material, and connective tissue (CT)/other at the healing site using histomorphometric examination of bone core biopsies obtained during osteotomy preparation. RESULTS: For allografts, the use of demineralized bone alone or in combination with mineralized is associated with more vital bone formation than the use of mineralized allograft alone. For mineralized allografts, the use of cortical versus cancellous bone has only minimal impact on new bone formation. Xenografts from bovine and porcine sources appear to have similar vital bone formation. Longer healing times prior to implant placement are associated with increased vital bone formation and decreased residual graft material. The most stable component in most studies is the percentage of CT/other. CONCLUSIONS: The percentage of vital bone and residual graft at ARP sites is dependent on the materials used and the length of healing time prior to obtaining core biopsies. KEY POINTS: What factors may affect the amount of new bone at the ARP site? At a time point about 4 months after ARP, the type of graft material used for ARP plays a large role in new bone formation. Studies focus on means and standard deviations, but patients often do not "follow the mean." Even if a single ARP protocol is used for all patients, there is great interindividual variability in new bone formation, and there is often variability between sites within a single patient. How long after ARP with an allograft should I wait to place an implant? Longer healing times such as 4-5 months generally provide higher amounts of vital bone formation than shorter healing times like 2-3 months. Differences in vital bone formation between ARP protocols tend to decrease with longer healing time. FDBA that contains demineralized bone, either alone or combined with mineralized FDBA, often provides higher amounts of new bone formation than 100% mineralized allograft, especially at shorter healing periods. Even a year after ARP with an allograft, residual graft material is often still present at the ARP site.

A radiographic and histological study to compare red (650 nm) versus near infrared (810 nm) diode lasers photobiomodulation for alveolar socket preservation.

Previous findings indicated that the laser photobiomodulation is more effective than the control or placebo in preserving the alveolar socket. This study aimed to compare two different lasers regarding their effectiveness in aiding alveolar socket preservation. Twenty extraction sockets were selected then divided into two equal groups. Group A was exposed to 650 nm Diode laser, and Group B to 810 nm Diode laser following the same protocol and parameters after a standard alveolar socket preservation procedure with collagen plug. Radiographic analysis with cone beam computed tomography was done to compare the alveolar bone surface area immediately after extraction and three months post-operatively, while bone samples collected before implant drilling were histologically examined for newly formed bone evaluation and histomorphometric analysis in terms of percentage of new bone surface area, percentage of unmineralized bone and finally, immunohistochemical analysis of Osteocalcin reaction surface area as well as optical density. Radiographically, infrared (810 nm) Diode effect on alveolar bone surface area has significantly exceeded the red laser, while histologically, red (650 nm) Diode has demonstrated statistical significance regarding all parameters; newly formed bone surface area percentage, unmineralized bone area percentage and finally Osteocalcin bone marker reaction surface area percentage and optical density. Under the specified conditions and laser parameters, photobiomodulation using the 810 nm Diode got the upper hand radiographically, yet histologically, the red 650 nm Diode managed to dominate all histological parameters when both employed as an adjunct to alveolar socket preservation procedures.

Alveolar ridge preservation of two-wall bone defects using mineralized dentin matrix: An experimental pre-clinical study.

OBJECTIVES: To study bone healing of two-wall bone defects after alveolar ridge preservation using mineralized dentin matrix. MATERIALS AND METHODS: After distal roots extraction of second and fourth premolars (P2, P4) on one lateral mandible in 12 beagles, two-wall bone defects (5 × 5 × 5 mm) were surgically created distally to the remaining mesial roots of P2 and P4. A total of 24 sites were randomly allocated to three groups (implant material- time of execution): mineralized dentin matrix (MDM)-3 m (MDM + collagen membrane; 3 months), MDM-6 m (MDM particles + collagen membrane; 6 months), and C-6 m (collagen membrane only; 6 months). Clinical, radiographic, digital, and histological examinations were performed 3 and 6 months after surgery. RESULTS: The bone healing in MDM groups were better compared to Control group (volume of bone regenerated in total: 25.12 mm3 vs. 13.30 mm3, p = .046; trabecular volume/total volume: 58.84% vs. 39.18%, p = .001; new bone formation rate: 44.13% vs. 31.88%, p = .047). Vertically, the radiological bone level of bone defect in MDM-6 m group was higher than that in C-6 m group (vertical height of bone defect: 1.55 mm vs. 2.74 mm, p = .018). Horizontally, no significant differences in buccolingual bone width were found between MDM and C groups at any time or at any level below the alveolar ridge. The percentages of remaining MDM were <1% in both MDM-3 m and MDM-6 m groups. CONCLUSIONS: MDM improved bone healing of two-wall bone defects and might be considered as a socket fill material used following tooth extraction.

Effects of boric acid on alveolar sockets filling after dental extraction in rats.

PURPOSE: After extraction, dental alveolus filling aims to reduce bone loss and maintain the alveolus volume during patient rehabilitation. Boric acid (BA) is a boron-derived compound with osteogenic properties and an interesting candidate for alveoli filling. This study aims to investigate the osteogenic capacity of the local application of BA in dental socket preservation. METHODS: Thirty-two male Wistar rats were submitted to upper right incisor extraction and randomly divided into four groups (n = 8): control group (no intervention), BA (8 mg/kg) socket filling, bone graft (Cerabone®, Botiss, Germany), and BA + bone graft socket filling. Animals were euthanized 28 days after dental extraction. MicroCT and histological analysis were performed to evaluate the newly formed bone on the dental alveolus. RESULTS: MicroCT analysis demonstrated that bone volume fraction (BV/TV), bone surface (BS), bone surface/bone volume ratio (BS/BV), bone surface density (BS/TV), trabecular thickness (Tb.Th), total bone porosity (Po-tot), and total volume of pore space (Po.V(tot)) from BA and BA + bone graft rats were significantly different from the control group. Histological evaluation displayed a delayed bone repair in BA rats, with the presence of connective tissue and inflammatory infiltrate. However, the BA + bone graft group demonstrated histological aspects like the bone graft animals, with less organized osteoblasts, suggesting inferior bone repair. CONCLUSION: Osteogenic capacity did not depend on the BA local application after 28 days of dental extraction. The presence of inflammation in the BA group can represent toxicity induced by the substance dosage used.

Recombinant bone matrix maintains the graft space, induces vascularized bone regeneration and preserves canine tooth extraction socket structure.

AIM: Recombinant bone matrix (RBM) is a newly conceived and engineered porous bone graft granule of average size 600 µm composed of purified recombinant collagen peptide. We sought to examine the behaviour with time of RBM that was grafted in the canine tooth extraction socket. MATERIALS AND METHODS: The canine tooth extraction socket of the hemisectioned mandibular third premolar distal root was grafted with RBM granules, whereas the opposite side extraction socket served as non-grafted control. The mandibular samples were harvested at 1, 3 and 6 months of healing and subjected to micro-CT imaging and decalcified paraffin-embedded histology. Separately, the effect of RBM was compared with that of deproteinized cancellous bovine bone (DCBB) and bovine atelocollagen plug (BACP) in the canine tooth extraction model at 3 months of healing. RESULTS: RBM maintained the grafted space in the socket and the gingival connective tissue until new bone was formed within its porous space. The regenerated bone was highly vascularized and continued to mature, while RBM was completely bioresorbed by 6 months. The buccal and lingual alveolar ridge heights of the RBM-grafted extraction socket was better preserved than those of non-grafted control sockets. The degree of socket preservation by RBM was equivalent to that by DCBB, although their healing mechanisms were different. CONCLUSIONS: This study demonstrated that RBM induced controlled active bone regeneration and preserved the extraction socket structure in a canine model. Bioresorbable RBM engineered without animal or human source materials presents a novel bone graft category with robust bone regenerative property.

Demineralized dentin matrix promotes gingival healing in alveolar ridge preservation of premolars extracted for orthodontic reason: a split-mouth study.

Objective: The purpose of this study was to prospectively evaluate the efficacy of a demineralized dentin matrix (DDM) in decreasing the initial inflammatory response of the gingiva and facilitating the repair and regeneration of soft tissue in alveolar ridge preservation. Methods: This clinical study employed a split-mouth design. Fourteen patients with a total of forty-four sites underwent extraction and alveolar ridge preservation (ARP) procedures. A Bilaterally symmetrical extraction operation were conducted on the premolars of each patient. The experimental group received DDM as a graft material for ARP, while the control group underwent natural healing. Within the first month postoperatively, the pain condition, color, and swelling status of the extraction sites were initially assessed at different time points Subsequently, measurements were taken for buccal gingival margin height, buccal-lingual width, extraction socket contour, and the extraction socket area and healing rate were digitally measured. Additionally, Alcian Blue staining was used for histological evaluation of the content during alveolar socket healing. Results: Both groups experienced uneventful healing, with no adverse reactions observed at any of the extraction sites. The differences in VAS pain scores between the two groups postoperatively were not statistically significant. In the early stage of gingival tissue healing (3 days postoperatively), there were statistically significant differences in gingival condition and buccal gingival margin height between the two groups. In the later stage of gingival tissue healing (7, 14, and 30 days postoperatively), there were statistically significant differences in buccal-lingual width, extraction socket healing area, and healing rate between the two groups. Furthermore, the histological results from Alcian Blue staining suggested that the experimental group may play a significant role in promoting gingival tissue healing, possibly by regulating inflammatory responses when compared to the control group. Conclusion: The application of DDM in alveolar ridge preservation has been found to diminish initial gingival inflammation after tooth extraction. Additionally, it has shown the ability to accelerate early gingival soft tissue healing and preserve its anatomical contour. Clinical trial registration: chictr.org.cn, identifier ChiCTR2100050650.

Effects of different doses of ionizing radiation on alveolar bone repair in post-extraction tooth socket: an experimental study in rats.

OBJECTIVE: This study aimed to evaluate the dose-response effects of ionizing radiation (IR) on alveolar bone repair and bone strength after tooth extraction. MATERIALS AND METHODS: A total of 32 male Wistar rats were used in the study, 28 animals were included in the final analysis, and n = 7 for each experimental group. Mandibular first molars were extracted. After 7 days, the animals were randomly divided into four groups according to single-dose irradiation: NIr, control group; Ir15, irradiated at 15 Gy; Ir20, irradiated at 20 Gy; and Ir30, irradiated at 30 Gy. The tooth extraction sites were subjected to micro-computed tomography (micro-CT), histological, histomorphometric, and biomechanical analyses 14 days after extraction. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test (α = 0.05). RESULTS: Micro-CT analysis revealed that IR led to lower values of bone volume (BV, in mm3) (0.68 ± 0.08, P < 0.001) and bone volume fraction, ratio of the segmented bone volume to the total volume of the region of interest (BV/TV, in %) (44.1 ± 8.3, P < 0.001) for the Ir30 group compared to the control group. A significantly lower amount of newly formed bone was observed in the Ir30 (P = 0.005) than in the Ir15 group. The histomorphometric results of quantification of bone matrix neoformation and the micro-CT were in agreement, demonstrating greater damage to the Ir30 group. IR30 cells showed a lower percentage of densely packed collagen than control cells. No significant differences were found in the biomechanical parameters. CONCLUSION: IR affects alveolar bone repair. A dose of 30 Gy reduced the bone healing process owing to a smaller amount of newly formed bone and a lower percentage of densely packed collagen. Therefore, a dose of 30 Gy can be used to successfully establish an animal model of an irradiated mandible that mimics the irradiated clinical conditions. CLINICAL RELEVANCE: Radiotherapy can lead to severe side effects and tooth extraction is a major risk factor. A proper understanding of the pathological mechanisms of radiation in alveolar bone repair requires the establishment of a suitable animal model of clinical conditions.

Evaluation of alveolar ridge preservation in sockets with buccal dehiscence defects using two types of xenogeneic biomaterials: An in vivo experimental study.

OBJECTIVES: Alveolar ridge preservation (ARP) has been extensively investigated in various preclinical and clinical studies, yielding favorable results. We aim to evaluate the effects of ARP using collagenated bovine bone mineral (CBBM) alone or particulated bovine bone mineral with a non-cross-linked collagen membrane (PBBM/NCLM) in tooth extraction sockets with buccal dehiscence in an experimental dog model. MATERIALS AND METHODS: The mesial roots of three mandibular premolars (P2, P3, and P4) were extracted from six mongrel dogs 4 weeks after inducing dehiscence defects. ARP was randomly performed using two different protocols: 1) CBBM alone and 2) PBBM/NCLM. Three-dimensional (3D) volumetric, micro-computed tomography, and histological analyses were employed to determine changes over a span of 20 weeks. RESULTS: In 3D volumetric and radiographic analyses, CBBM alone demonstrated similar effectiveness to PBBM/NCLM in ARP (p > .05). However, in the PBBM/NCLM group (3.05 ± 0.60 mm), the horizontal ridge width was well maintained 3 mm below the alveolar crest compared with the CBBM group (2.11 ± 1.01 mm, p = .002). CONCLUSION: Although the radiographic changes in the quality and quantity of bone were not significant between the two groups, the use of PBBM/NCLM resulted in greater horizontal dimensions and more favorable maintenance of the ridge profile.

Alveolar Ridge Preservation Procedures Performed with a Freeze-Dried Bone Allograft: Histologic Outcomes in a Cohort Study.

The primary aim of this study was to assess the histomorphometric outcomes of extraction sockets grafted with freeze-dried bone allograft (FDBA) and sealed with a collagen membrane after 3 months of healing in specific region of interest (ROI) areas. The secondary aims were to analyze the biomaterial resorption rate, the bone-to-biomaterial contact (BBC), and the area and perimeter of grafted particles compared with commercially available FDBA particles. Fifteen patients underwent tooth extractions and ridge preservation procedures performed with FDBA and a collagen membrane. Bone biopsy samples were harvested after 3 months at the time of implant placement for histologic and histomorphometric analysis. Two areas of concern (ROI1 and ROI2) with different histologic features were identified within the biopsy samples; ROI1, ROI2, and commercially available particles were analyzed and compared. The following parameters were analyzed: newly formed bone, marrow space, residual graft particles, perimeter and area of FDBA particles, and BBC. The histomorphometric analysis showed 35.22% ± 10.79% newly formed bone, 52.55% ± 16.06% marrow spaces, and 12.41% ± 7.87% residual graft particles. Moreover, the histologic data from ROI1 and ROI2 showed that (1) the mean percentage of BBC was 64.61% ± 27.14%; (2) the newly formed bone was significantly higher in ROI1 than in ROI2; (3) the marrow space was significantly lower in ROI1 than in ROI2; and (4) the FDBA particles in ROI1 sites showed significantly lower area and perimeter when compared to commercially available FDBA particles. This latter data led to the hypothesis that FDBA particles embedded in newly formed bone undergo a resorption/remodeling process.

Bone remodelling marker expression in grafted and ungrafted sheep tooth extraction sockets: A comparative randomised study.

OBJECTIVE: To compare key markers of bone remodelling in a sheep tooth extraction model for sockets left to heal naturally or grafted with the bovine-derived xenograft Bio-Oss® covered with a collagen Bio-Gide® membrane. DESIGN: Right side premolar teeth were removed from thirty Romney-cross ewes. Standardised sockets in each sheep were randomly allocated treatments, a grafted test and an empty control. At 4-, 8- and 16-weeks sheep were euthanized and tissue collected (N = 10/group). RANK, RANKL and OPG immunohistochemical analysis was performed (n = 3). RANK, RANKL, OPG, COL1A1, TIMP3, SP7 and MSX2 mRNA expression levels were determined using RT2-qPCR assays (n = 3). RESULTS: Histologically, more new woven bone was observed in the test group at all time points. Strong RANK and RANKL expression was found in both groups; at all time points with stronger RANK staining in the test group at 8 and 16 weeks. Strong OPG staining was localized to both osteoblasts and connective tissues. RANK receptor mRNA was expressed at a lower level in the test group (-4.26-fold; p = 0.02) at 4 weeks and SP7 at 16 weeks (-2.89-fold; p = 0.04). COL1A1 and TIMP3 mRNA expression increased significantly over time in the control group (p = 0.045, F = 5.4 and p = 0.003, F = 42.2 respectively). CONCLUSION: Socket healing over time was comparable. The sheep tooth extraction model was found to be suitable for the evaluation of changes in the alveolar bone at the molecular level.

Influence of age and gender on alveolar bone healing post tooth extraction in 129 Sv mice: a microtomographic, histological, and biochemical characterization.

OBJECTIVES: To analyze the effect of biological sex and aging on craniofacial bone features in 129 Sv mice and their influence on dental socket healing post tooth extraction. MATERIALS AND METHODS: A total of 52 129 Sv mice were used, of which 28 were young (3-4 months) and 24 were aged (17-18 months), equally distributed according to biological sex. After an upper right incisor extraction, mice specimens were collected at 7, 14, and 21-days post-surgery for microtomographic (microCT) and comprehensive histological analysis. Mandible, skull bones, and maxillae at 21 days were analyzed by microCT, while blood plasma samples were collected for the detection of key bone turnover markers (P1NP and CTX-1) by enzyme-linked immunosorbent (ELISA) assay. RESULTS: Aged females depicted significantly decreased mineralized bone content in alveolar sockets in comparison to young females and aged males at day 7, and aged males at day 14. Mandible RCA and Ma.AR of aged females were also significantly decreased in comparison with young females. Histological evaluation revealed that all alveolar sockets healed at 21 days with inflammation resolution and deposition of new bone. Immunohistochemistry for TRAP revealed increased area density for osteoclasts in alveolar sockets of aged females when compared to young females at 21 days. While a significant increase in CTX-1 levels was detected in blood plasma of aged females when compared to young females, P1NP levels did not significantly change between young and older females. No significant changes were observed for males. CONCLUSIONS: Age and gender can significantly affect craniofacial bones of 129 Sv mice, especially maxilla and mandible in females. Considering the altered bone resorption parameters and delayed alveolar bone healing in older females, careful deliberation is necessary during development of pre-clinical models for craniofacial research. CLINICAL RELEVANCE: Aging can be a contributing factor to slower bone healing in craniofacial bones. However, there are no sufficient experimental studies that have addressed this phenomenon along with biological sex taken into consideration.

Intrasocket reactive tissue: The state of current knowledge.

This review focuses on intrasocket reactive tissue and its impact on extraction socket healing. It summarises the current knowledge about intrasocket reactive tissue from a histopathological and biological perspective and discusses the mechanisms by which residual intrasocket reactive tissue can have a positive or negative effect on healing. Additionally, it provides an overview of the various hand and rotary instruments that are currently used for intrasocket reactive tissue debridement. The review also discusses preserving intrasocket reactive tissue as a socket sealing material and the benefits this may offer. It presents clinical cases where either removal or preservation of intrasocket reactive tissue was adopted following extraction and prior to alveolar ridge preservation. Future studies are needed to investigate the suggested beneficial effects of intrasocket reactive tissue on socket healing outcomes.

Clinical evaluation of different alveolar ridge preservation techniques after tooth extraction: a randomized clinical trial.

OBJECTIVE: The aim of the present randomized controlled trial (RCT) was to evaluate the efficacy of different alveolar ridge preservation (ARP) techniques on dimensional alterations after tooth extraction, based on clinical measurements. BACKGROUND: Alveolar ridge preservation (ARP) is a common procedure in every day clinical practice, when dental implants are involved in treatment planning. In ARP procedures, a bone grafting material is combined with a socket sealing (SS) material in order to compensate the alveolar ridge dimensional alterations after tooth extraction. Xenograft and allograft are the most frequently used bone grafts in ARP, while free gingival graft (FGG), collagen membrane, and collagen sponge (CS) usually applied as SS materials. The evidence comparing xenograft and allograft directly in ARP procedure is scarce. In addition, FGG is usually combined with xenograft as SS material, while the evidence combing allograft with FGG is absent. Moreover, CS could probably be an alternative choice in ARP as SS material, since it has been used in previous studies but more clinical trials are required to evaluate its effectiveness. MATERIALS AND METHODS: Forty-one patients were randomly assigned in four treatment groups: (A) freeze-dried bone allograft (FDBA) covered with collagen sponge (CS), (B) FDBA covered with free gingival graft (FGG), (C) demineralized bovine bone mineral xenograft (DBBM) covered with FGG, and (D) FGG alone. Clinical measurements were performed immediately after tooth extraction and 4 months later. The related outcomes pertained to both vertical and horizontal assessment of bone loss. RESULTS: Overall, groups A, B, and C presented significantly less vertical and horizontal bone resorption compared to group D. No statistically significant difference was observed between allograft and xenograft, except for the vertical bone resorption at the buccal central site, where xenograft showed marginally statistically significantly reduced bone loss compared to allograft (group C vs group B: adjusted ß coef: 1.07 mm; 95%CI: 0.01, 2.10; p = 0.05). No significant differences were observed in hard tissue dimensions when CS and FGG were applied over FDBA. CONCLUSIONS: No differences between FDBA and DBBM could practically be confirmed. In addition, CS and FGG were equally effective socket sealing materials when combined with FDBA, regarding bone resorption. More RCTs are needed to compare the histological differences between FDBA and DBBM and the effect of CS and FGG on soft tissue dimensional changes. CLINICAL RELEVANCE: Xenograft and allograft were equally efficient in ARP 4 months after tooth extraction in horizontal level. Xenograft maintained the mid-buccal site of the socket marginally better than the allograft, in vertical level. FGG and CS were equally efficient as SS materials regarding the hard tissue dimensional alterations. TRIAL REGISTRATION: Clinical trial registration Number: NCT04934813 (clinicaltrials.gov).

Dose-response effect of Montelukast on post-extraction dental socket repair and skeletal phenotype of mice.

Bone metabolism and repair are directly regulated by arachidonic acid metabolites. At present, we analyzed the dose-response effects of a selective cysteinyl leukotriene receptor type-1 antagonist during bone repair after tooth extraction and on non-injured skeleton. Sixty-three 129 Sv/Ev male mice composed the groups: C-Control (saline solution); MTK2-2 mg/Kg of Montelukast (MTK) and MTK4-4 mg/Kg of MTK, daily administered by mouth throughout all experimental periods set at 7, 14, and 21 days post-operative. Dental sockets were analyzed by computed microtomography (microCT), histopathology, and immunohistochemistry. Femurs, L5 vertebra and organs were also removed for observation. Blood was collected for plasma bone and liver markers. Histopathology and microCT analysis revealed early socket repair of MTK2 and MTK4 animals, with significant increased BV/TV at days 14 and 21 compared to C. Higher plasma calcium was detected at days 7 and 21 in MTK4 in comparison to C, while phosphate was significantly increased in MTK2 in the same periods in comparison to C and MTK4. No significant differences were found regarding plasma ALP and TRAP, neither for local TRAP and Runx2 immunolabeling at the healing sockets. Organs did not present histological abnormalities. Increased AST levels have been detected in distinct groups and periods. In general, femur phenotype was improved in MTK treated animals. Collectively, MTK promoted early bone formation after tooth extraction and increased bone quality of femurs and vertebra in a time-dose-dependent manner, and should be considered as an alternative therapy when improved post-extraction socket repair or skeleton preservation is required.