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.

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.

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.

Alveolar regeneration of the post-extraction site with cortical deficiency using the Lamina Socket Sealing technique: Retrospective study with histomorphometric analysis of regenerated bone and evaluation of soft tissue changes. Part 2/2.

PURPOSE: This retrospective observational study evaluated the histomorphometric and soft tissue outcome of a new alveolar ridge preservation (ARP) technique, "Lamina Socket Sealing" (LSS) technique, using a porcine barrier. METHODS: Patients with maxillary premolars to be extracted and extensive alveolar wall defects were enrolled and treated. Porcine-derived barriers and mesenchymal membrane were used to seal the extraction socket with alveolar particulate graft. An optical scan of the dental arches was performed with an intraoral scanner (Trios 3, 3Shape) at baseline and at a 4-month follow-up. At the time of implant placement, a bone sample was taken at the implant site with a trephine drill (Hager & Meisinger) and subjected to histomorphometric analysis. RESULTS: 36 subjects (21 females and 15 males) were treated. At 4 months, histomorphometric analysis of the bone samples revealed that the percentage of vital bone was 42.87%, 8.75% of residual granules, 30.76% of soft tissue. Linear comparison of the width of the keratinized gingiva showed an increase (mean + SE) of 3.16 ± 0.35 mm. The net volumetric change of soft tissue was (mean + SE) +28.41 ± 19.52 mm³. CLINICAL SIGNIFICANCE: This alveolar ridge preservation technique (Lamina Socket Sealing) using a resorbable heterologous cortical lamina with a flapless approach has proven effective in maintaining adequate soft tissue and grafting of particulate bone and lamina, with a high percentage of viable bone.

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.

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.

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.

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.

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.

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.

Healing of particulate allografts mixed with platelet concentrates in ridge preservation and sinus lift: a prospective histomorphometric study.

The objective of the present study was to evaluate the bone quality of sinus and alveolar grafts following filling with particulate allogenous bone (DFDBA 300-500µm) and platelet concentrate (platelet-rich fibrin, PRF). A prospective interventional clinical study was carried out. A total of 40 bone cores, 2mm in diameter, were taken from 21 patients: 22 from grafted alveoli, 7 from grafted sinus sites, and 11 from native bone used as a control. Fixed, paraffin-embedded samples were subjected to histological staining with hematoxylin-eosin and Masson's trichrome. Bone maturity of the samples was evaluated by two independent operators using histomorphometric analysis. There existed a greater proportion of lamellar neoformed bone than woven neoformed bone as the healing time increased. Moreover, there was also an increasing proportion of newly formed bone in the grafted sockets as a function of healing time (average: 41.22% ≤ 5 months, 55.89% Ëƒ 5 months). Resorption of DFDBA particles also appears to be correlated with healing time in the grafted socket (average: 15.43 ≤ 5 months, 13.72% Ëƒ 5 months). In conclusion, performing sinus lift and alveolar socket preservation techniques using DFDBA and PRF results in high quality, mature bone tissue according to histological criteria.

Ridge preservation in molar sites comparing xenograft versus mineralized freeze-dried bone allograft: A randomized clinical trial.

OBJECTIVES: The main objective of the study was to compare the dimensional ridge changes and the histological composition after the use of an allograft or xenograft and a resorbable membrane in ridge preservation in molar sites and to evaluate the influence of bone plate thickness on dimensional changes and the need of lateral sinus augmentation following ridge preservation. MATERIALS AND METHODS: Twenty-four patients in need of maxillary or mandibular first or second molar extraction and subsequent implant placement were included and randomly assigned to a group; allograft or xenograft, plus a collagen membrane. Cone-beam computed tomographies were obtained after molar extraction and after 5 months. A bone sample was harvested at the time of implant placement and analyzed by histomorphometry. RESULTS: Bone ridge was reduced significantly. Major changes in width occurred at 1 mm from the bone crest (-2.93 ± 2.28 mm) (p = .0002), while in height, the greatest reduction occurred at the buccal area (-1.97 ± 2.21 mm) (p = .0006). However, differences between groups were not significant. Thicker buccal bone plates exhibited less bone remodeling, while histologically, both biomaterials resulted in similar tissue composition. The resulting available bone height in the implant site measured 7.30 ± 3.53 mm initially and 6.8 ± 3.61 mm after 5 months which allowed implant placement without the need for lateral sinus augmentation in all cases. Still, 55% of the preserved areas needed transcrestal sinus lift. CONCLUSION: Ridge preservation in molar sites using a mineralized allograft or xenograft provides similar dimensional and histomorphometrical results after 5 months.

LED photobiomodulation therapy combined with biomaterial as a scaffold promotes better bone quality in the dental alveolus in an experimental extraction model.

A bone scaffold added to the dental alveolus immediately after an extraction avoids bone atrophy and deformity at the tooth loss site, enabling rehabilitation with implants. Photobiomodulation accelerates bone healing by stimulating blood flow, activating osteoblasts, diminishing osteoclastic activity, and improving the integration of the biomaterial with the bone tissue. The aim of the present study was to evaluate the effect of photobiomodulation with LED at a wavelength of 850 nm on bone quality in Wistar rats submitted to molar extraction with and without a bone graft using hydroxyapatite biomaterial (Straumann® Cerabone®). Forty-eight rats were distributed among five groups (n = 12): basal (no interventions); control (extraction) (basal and control were the same animal, but at different sides); LED (extraction + LED λ = 850 nm); biomaterial (extraction + biomaterial), and biomaterial + LED (extraction + biomaterial + LED λ = 850 nm). Euthanasia occurred at 15 and 30 days after the induction of the extraction. The ALP analysis revealed an improvement in bone formation in the control and biomaterial + LED groups at 15 days (p = 0.0086 and p = 0.0379, Bonferroni). Moreover, the LED group had better bone formation compared to the other groups at 30 days (p = 0.0007, Bonferroni). In the analysis of AcP, all groups had less resorption compared to the basal group. Bone volume increased in the biomaterial, biomaterial + LED, and basal groups in comparison to the control group at 15 days (p < 0.05, t-test). At 30 days, the basal group had greater volume compared to the control and LED groups (p < 0.05, t-test). LED combined with the biomaterial improved bone formation in the histological analysis and diminished bone degeneration (demonstrated by the reduction in AcP), promoting an increase in bone density and volume. LED may be an important therapy to combine with biomaterials to promote bone formation, along with the other known benefits of this therapy, such as the control of pain and the inflammatory process.

Distribution of mature and newly regenerated nerve fibres after tooth extraction and dental implant placement: An immunohistological study.

BACKGROUND: The time-dependent peri-implant innervation needs to be elucidated in detail. OBJECTIVES: To examine the distribution of mature and newly regenerated nerves around the implant with immunofluorescence during 28-day follow-up after implantation. METHODS: 35 male Sprague-Dawley rats were grouped into non-operated (n = 5), extraction (n = 5) and implant (n = 25) groups. For rats in the extraction and implant groups, three right maxillary molars were extracted. One month later, a titanium implant was placed into the healed alveolar ridge in the implant group. The implant group was further divided into 5 subgroups according to day 1, 3, 7, 14 or 28 after implantation, on which day serial histological sections were prepared for immunohistochemistry. On day 28, the serial sections were also prepared in the non-operated and extraction groups. Soluble protein-100 and growth-associated protein-43 were used to immunolabel mature and newly regenerated nerve fibres, respectively. RESULTS: In the peri-implant soft tissues, the number of both mature and newly regenerated nerves showed an increasing trend in 28 days. In the bone tissues, the number of mature or newly regenerated nerves in both areas at less than 100 µm and 100-200 µm from the implant surface on day 28 grew significantly compared with that on day 1 or 3. In addition, the closest distance from mature nerves to the implant surface decreased evidently. CONCLUSION: The number of peri-implant nerves increased in 28 days since implantation. The innervation in the soft tissue took place faster than in the bone tissue. The mature nerves in the bone tissue approached the implant gradually.

Comparison of Injectable Biphasic Calcium Phosphate and a Bovine Xenograft in Socket Preservation: Qualitative and Quantitative Histologic Study in Humans.

This study is the first histologic evaluation of an injectable biphasic calcium phosphate (IBCP) in humans six months after socket preservation according to the principles of guided bone regeneration. After tooth extraction, the alveolar ridge of 21 patients was augmented with IBCP (maxresorb® inject) in the test group, while 20 patients in the control group received a bovine xenograft (BX) (cerabone®). Six months after augmentation, a reentry procedure was performed to collect biopsies of regenerated bone for qualitative and quantitative histologic analysis. A total of 20 biopsies were taken for analysis. Qualitative histologic analysis showed complete integration of the biomaterial and no inflammatory tissue reaction, indicating the biocompatibility of the bone grafts and the surrounding tissue in both groups. Histomorphometric analysis showed comparable results in terms of newly formed bone (IBCP: 26.47 ± 14.71%, BX: 30.47 ± 16.39%) and residual biomaterial (IBCP: 13.1 ± 14.07%, BX: 17.89 ± 11.81%), with no significant difference found across groups (p > 0.05, Mann­Whitney U test). Statistical significance between groups was found in the result of soft tissue percentage (IBCP: 60.43 ± 12.73%, BX: 51.64 ± 14.63%, p = 0.046, Mann­Whitney U test). To conclude, IBCP and BX showed good osteoconductivity and biocompatibility with comparable new bone formation six months after alveolar ridge preservation.

Tissue reaction to novel customized calcium silicate cement based dental implants. A pilot study in the dog.

OBJECTIVES: The purpose of this study was to determine the level of periodontal tissue regeneration in a canine model following post-extraction placement of an implant molded from a composite material made from extracted tooth dentin and a calcium silicate cement (CSC) material. The investigation used autologous dentin in conjunction with a CSC material to form a composite implant designed for immediate tooth replacement. METHODS: Two (2) beagles had a periodontal and radiographic examination performed to rule out any pre-treatment inflammation, significant periodontal disease, or mobility. Then, ination eleven (11) teeth were extracted and polyvinyl siloxane molds were made to fabricate three different types of implants: Particulate Implant (Test Group 1, n = 4), Shell Implant Alone (Test Group 2, n = 2), Shell Implant with Emdogain® (Test Group 3, n = 3). Teeth in the control group were extracted, scaled (n = 2), and then re-implanted into their respective fresh extraction sockets. At 4 weeks, a clinical, radiographic, and histologic assessment was performed. RESULTS: Clinical evaluation revealed no mobility in any of the test or control implants and no radiographic evidence of significant bone loss or active disease. Based on the MicroCT analysis, direct bone to implant contact was observed in some areas with an apparent periodontal ligament space. Implant-related inflammation, on average, was similar among all groups, with low numbers of infiltrates. Implant-related inflammatory reaction was generally minimal and not interpreted to be adverse. CONCLUSION: The proposed novel composite materials revealed that not only do these materials demonstrate high biocompatibility, but also their successful integration in the alveolus is likely secondary to a partial ligamentous attachment. The current investigation may lead to the use of calcium silicate-based materials as custom dental implants. Further research on this novel composite's biomechanical properties is necessary to develop the optimal material composition for use as a load-bearing dental implant.

Photobiomodulation as an adjunctive therapy for alveolar socket preservation: a preliminary study in humans.

Bone remodeling results in loss of alveolar bone height and thickness. Photobiomodulation (PBM) based on photochemical stimulation by low-intensity lasers emerges as an adjunctive therapy for alveolar socket preservation. Our study aimed to evaluate the effects of PBM therapy on alveolar bone repair. Twenty healthy patients in need of bilateral extraction of lower molars were enrolled in this split-mouth randomized and blind clinical trial. The extraction sites were randomly selected to receive either the PBM therapy with a CW GaAIAs diode laser (808 nm; 0.028 mm2; 0.1 W; 3.6 W/cm2; 89 J/cm2; 2.5 J/point) or no treatment (Control). Bone biopsies were harvested 45 days after the dental extraction and evaluated using micro-computerized tomography (µCT), morphometric, and histological analysis. Data were compared using the paired t test, and the level of significance was set at 5%. Bone surface (p = 0.029), bone surface/total volume (p = 0.028), trabecular number (p = 0.025), and connectivity density (p = 0.029) were higher at the PBM group compared with Control. The histological observations confirmed the µCT findings. PBM samples exhibited higher number of organized and connected bone trabeculae along with higher density of blood vessels than Control. Control samples displayed a dense and highly cellular connective tissue at the central area accompanied by the presence of immature bone trabeculae at the periphery. Our results indicated that the PBM therapy improved the newly bone trabeculae formation and their connectivity which increased bone surface, indicating the positive effect of the laser on alveolar human socket repair.

The Influence of Local Pamidronate Application on Alveolar Dimensional Preservation after Tooth Extraction-An Animal Experimental Study.

The aim of this randomized, controlled animal exploratory trial was to investigate the influence of local application of aminobisphosphonate pamidronate during the socket preservation procedure. Mandibular premolars were extracted in five Göttingen minipigs. Two animals underwent socket preservation using BEGO OSS (n = 8 sockets) and three animals using BEGO OSS + Pamifos (15 mg) (n = 12 sockets). After jaw impression, cast models (baseline, eight weeks postoperative) were digitized using an inLab X5 scanner (Dentsply Sirona) and the generated STL data were superimposed and analyzed with GOM Inspect 2018 (GOM, Braunschweig). After 16 weeks, the lower jaws were prepared and examined using standard histological methods. In the test group (BEGO OSS + pamidronate), buccooral dimensional loss was significantly lower, both vestibulary (0.80 ± 0.57 mm vs. 1.92 ± 0.63 mm; p = 0.00298) and lingually (1.36 ± 0.58 mm vs. 2.56 ± 0.65 mm; p = 0.00104) compared with the control group (BEGO OSS). The test group showed a significant difference between vestibular and lingual dimensional loss (p = 0.04036). Histology showed cortical and cancellous bone in the alveolar sockets without signs of local inflammation. Adjuvant application of pamidronate during socket preservation reduces alveolar dimensional loss significantly. Further investigations with regard to dose-response relationships, volume effects, side effects, and a verification of the suitability in combination with other bone substitute materials (BSMs) are necessary.

Alveolar bone healing in mice genetically selected in the maximum (AIRmax) or minimum (AIRmin) inflammatory reaction.

The exact role of inflammatory immune response in bone healing process is still unclear, but the success of the alveolar bone healing process seems to be associated with a moderate and transitory inflammatory response, while insufficient or exacerbated responses seems to have a detrimental influence in the healing outcome. In this context, we performed a comparative analysis of mice strains genetically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response to address the influence of inflammation genes in alveolar bone healing outcome. Experimental groups comprised 8-week-old male or female AIRmax and AIRmin submitted to extraction of upper right incisor, and evaluated at 0, 3, 7, 14 and 21 days after upper incision extraction by micro-computed tomography (µCT), histomorphometry, birefringence, immunohistochemistry and molecular (PCRArray) analysis. Overall, the results demonstrate a similar successful bone healing outcome at the endpoint was evidenced in both AIRmin and AIRmax strains. The histormophometric analysis reveal a slight but significant decrease in blood clot and inflammatory cells density, as well a delay in the bone formation in AIRmax strain in the early times, associated with a decreased expression of BMP2, BMP4, BMP7, TGFb1, RUNX2, and ALP. The evaluation of inflammatory cells nature reveals increased GR1+ cells counts in AIRmax strain at 3d, associated with increased levels of neutrophil chemoattractants such as CXCL1 and CXCL2, and its receptor CXCR1, while F4/80+ cell prevails in AIRmin strain at 7d. Also, our results demonstrate a relative predominance of M2 macrophages in AIRmin strain, associated with an increased expression of ARG1, IL10, TGFb, while M1 macrophages prevail in AIRmax, which parallel with increased IL-1B, IL-6 and TNF expression. At late repair stage, AIRmax presents evidences of increased bone remodeling, characterized by increased density of blood vessels and osteoclasts in parallel with decreased bone matrix density, as well increased levels of MMPs, osteoclastogenic and osteocyte markers. In the view of contrasting inflammatory and healing phenotypes of AIRmin and AIRmax strains in other models, the unpredicted phenotype observed suggests the existence of specific QTLs (Quantitative trait loci) responsible for the regulation 'sterile' inflammation and bone healing events. Despite the similar endpoint healing, AIRmax strain delayed repair was associated with increased presence of neutrophils and M1 macrophages, supporting the association of M2 cells with faster bone healing. Further studies are required to clarify the elements responsible for the regulation of inflammatory events at bone healing sites, as well the determinants of bone healing outcome.