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Expression of signaling proteins in bone cells depends on their embryological mesoderm-derived (e.g. tibia) or cranial neural crest (CNC)-derived (e.g. jaw) origin. Connexin 43 (Cx43) is a gap junction protein that plays an essential role in the mode of action of bisphosphonates (BP). This study aimed to investigate Cx43 expression and the influence of BP application on mesoderm- and CNC-derived bone. Using a rat model, molar extraction and tibia osteotomy with (Group 4) or without (Group 3) previous BP application was performed. Untreated (Group 1) and animals selectively treated with BPs (Group 2) served as controls. Cx43 expression was immunohistochemically determined 12 and 16 weeks postoperatively via a labeling index. Cx43 expression in CNC-derived bone was significantly higher compared with mesodermal bone. BP application decreased Cx43 expression; however, detected expression levels were still higher in jawbone (Group 2 tibia vs jaw: 5.83 ± 5.06 vs 23.52 ± 6.42; p = 0.007). During bone healing after surgical intervention (Group 3) there were no expression differences between tibia and jawbone. BP treatment prior to surgery resulted in significantly lower Cx43 expression in CNC-derived compared with tibia bone (Group 4 tibia vs jaw: 56.84 ± 15.57 vs 16.40 ± 5.66; p < 0.01). Increased Cx43 expression in jaw compared with tibia bone is in line with their embryological origins. A significant Cx43 suppression in jawbone after BP application and surgery might contribute to the selectively altered osseous turnover and development of MRONJ in CNC-derived bone., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to investigate intraluminal vessel diameters and endothelial expression levels of pro-inflammatory and -thrombotic mediators in patent and non-patent microvascular anastomoses. Endothelial expression of CD31, VCAM-1, E- and P-Selectin, eNOS, iNOS and PAI-1 was evaluated by immunohistochemistry and compared to non-anastomosed arteries as controls. Intraluminal diameters were determined via H.E.-staining. In 20 human anastomoses (8 patent, 12 non-patent) neither the analysis of endoluminal de-endothelialization (p = 0.966) nor luminal narrowing (p = 0.750) revealed any significant differences between patent and non-patent microanastomoses. Expressions of pro-inflammatory mediators were significantly higher in patent anastomoses compared to controls but did not show any difference compared to non-patent anastomoses (p > 0.050). iNOS was higher in non-patent compared to patent anastomoses (p = 0.030) and controls (p = 0.001), whereas eNOS did not reveal any differences between these groups (p = 0.611 and p = 0.130). In non-patent anastomoses PAI-1 was expressed higher compared to patent anastomoses and controls (p = 0.021 and p < 0.001). Irrespective of their patency, anastomoses are characterized by endothelial dysfunction with a pro-inflammatory and pro-thrombotic milieu. Avoiding endothelial trauma during suturing is essential in order not to aggravate existing endothelial dysfunction in microanastomoses. Additionally, the influence of medication-related changes on anastomoses should be investigated as this is still an indistinctive topic., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflict of interest to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study analyzed the expression of the PD1 receptor in tumor tissue and peripheral blood of oral squamous cell carcinoma (OSCC) patients, and correlated it with the PD1 ligands PD-L1 and PD-L2. The currently low response rates of checkpoint inhibitor treatment in OSCC could be increased by a better understanding of immune checkpoint biology. Despite evidence in the literature for upregulation of PD1 checkpoint ligands in OSCC tissue, there has been no correlation analysis of the PD1 receptor with its ligands in tissue specimens and peripheral blood of OSCC patients., Materials and Methods: An RT-qPCR analysis of PD1 mRNA expression was performed in oral cancer specimens, healthy mucosa, and corresponding blood samples. A cut-off point (COP) was determined and a chi-square (χ 2 ) test was carried out. PD1 expression was correlated with previously reported PD-L1 and PD-L2 expression values using the Spearman test., Results: Tissue and blood specimens of 48 OSCC patients and 26 healthy individuals were analyzed. PD1 expression in OSCC specimens was significantly increased (p = 0.006) compared with healthy oral mucosa. PD1 overexpression in tissue samples showed a significant association with the presence of malignancy (p = 0.006). PD1 expression in tissue samples showed a significant positive correlation (p < 0.001) with the ligands PD-L1 and PD-L2. In contrast, there was no correlation between PD1 and its ligands in blood samples. However, there was a significant positive correlation (p < 0.001) between the ligands PD-L1 and PD-L2, both in tissue and blood samples., Conclusions: Increased PD1 expression might be a manifestation of T-cell exhaustion in OSCC specimens, leading to immune tolerance. PD-L1/PD-L2-PD1 interaction may be a major mediator of local immunosuppression in OSCC, requiring advanced multimodal treatment protocols., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: One of the severe side effects of bisphosphonate (BP) therapy is bisphosphonate-associated osteonecrosis of the jaw (BONJ). However, there is no information available about its pathogenesis. Hence, the aim of this observational study was to contribute to discerning this pathogenesis by comparing salivary quantity and quality in patients with BONJ and undergoing BP treatment., Materials and Methods: This study included 60 patients divided into three groups. The first group consisted of 20 patients with established BONJ, the second group had 20 patients undergoing BP treatment, and the third group comprised 20 healthy individuals. These groups were analysed for the flow rate of stimulated saliva, buffer capacity, and salivary pH level., Results: Reduced salivation was observed in a significantly high number of patients with established BONJ (n = 8) and those undergoing BP treatment (n = 9) in comparison with the healthy control group (n = 4; p = 0.039). Though the distribution of the mean value of stimulated saliva flow rates in patients undergoing BP treatment was lower than in the control group, the difference was not significant. Moreover, there were no significant differences in the salivary pH level and buffer capacity in patients undergoing BP treatment as compared with the healthy control group., Conclusions: It is possible that the quantity of human saliva is affected by BP treatment. This reduction in saliva production could have a negative effect on mucosal health and is perhaps a cofactor in the pathogenesis of BONJ., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Purpose: Surgical treatment of medication-related osteonecrosis of the jaw (MRONJ) consists of necrotic bone removal followed by dense mucosal closure. Fluorescence-guided surgery has become a promising tool to intraoperatively distinguish between healthy and necrotic bone. Until now, there has been a lack of histopathological studies correlating the intraoperative fluorescence situation to histopathological analyses of the respective bone areas in order to further validate this method., Materials and Methods: Histopathological sections from intraoperatively detected fluorescence- and non-fluorescence-labeled bone were analyzed detecting osteocyte and collagen content, RANK(L) and TRAP expression as well as proportion of immature bone regeneration. Samples were compared with viable-looking bone areas according to the intraoperative clinical situation., Results: Staining revealed a significant decrease of osteocytes and collagen type-I fibers in necrotic, non-fluorescing areas compared to fluorescing bone (R/RGB [%]: 0.56 ± 0.38 (fluorescence positive) vs. 3.18 ± 2.22 (fluorescence negative), p = 0.041). Furthermore, the number of osteocytes was higher in fluorescing, clinically viable bone samples (cell/mm 2 : 151.26 ± 95.77 (fluorescence positive) vs. 0.56 ± 0.38 (fluorescence negative), p = 0.028). Additionally, the amount of immature bone was substantially increased in luminescent jaw bone (proportion of red [%]: 6.78 ± 7.00 (fluorescence positive) vs. 2.24 ± 1.36 (fluorescence negative), p = 0.442). RANK(L) and TRAP expression did not differ between the investigated areas, resembling a generalized decrease in osteocyte-osteoclast function all over the jaw (RANK(L) -positive cells per mm 2 : 8.97 ± 7.85 (fluorescence positive) vs. 7.76 ± 6.41 (fluorescence negative), p = 0.793; TRAP-positive cells per mm 2 : 0.36 ± 0.38 (fluorescence positive) vs. 0.33 ± 0.41 (fluorescence negative), p = 0.887)., Conclusion: Intraoperative fluorescence-guided surgery might be more precise in identifying and resecting the necrotic bone compared to previous indicators like bone bleeding, which could be useful to further improve surgical therapy in MRONJ patients., (Copyright © 2019 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: Dental cysts can be of inflammatory (radicular cysts) or noninflammatory (dentigerous cysts) origin. Apical periodontitis is a necrosis of the pulp and infection of the root canal causing the development of apical granulomas or radicular cysts. The immunology of granuloma and cyst formation is important because modern root filling materials are immunologically active and can contribute to the resolution of apical granulomas. In contrast, radicular cysts often require apicectomy. A better understanding of the pathophysiology of inflammation and bone resorption in apical periodontitis could be the basis for developing new root filling materials with superior immunomodulatory properties., Methods: Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray of the 87 consecutive specimens was created, and human leukocyte antigen-DR isotype (HLA-DR)-, CD83-, receptor activator of nuclear factor kappa B ligand-, macrophage colony-stimulating factor (MCSF)-, galectin-3 (Gal3)-, CD4-, and CD8-positive cells were detected by immunohistochemistry. Tissue microarrays were digitized, and the expression of markers was quantitatively assessed., Results: HLA-DR, CD83, MCSF, and Gal3 expression was significantly (P < .05) higher in radicular cysts compared with apical granulomas. HLA-DR, CD83, MCSF, receptor activator of nuclear factor kappa B ligand, and Gal3 expression in dentigerous cysts was significantly (P < .05) lower than in both periapical lesions (apical granulomas and radicular cysts). CD4 and CD8 infiltration was not statistically different between apical granulomas and radicular cysts. Dentigerous cysts showed a significantly (P < .05) lower T-cell infiltration than apical periodontitis. The CD4/CD8 ratio was not significantly different between the analyzed groups., Conclusions: The development of radicular cysts in apical periodontitis is associated with an increased expression of myeloid inflammatory markers and bone resorption parameters. Antigen-presenting cells and myeloid cells might be more relevant for the pathogenesis of apical periodontitis than T cells. Increased inflammation might promote the formation of radicular cysts and more pronounced bone resorption., (Copyright © 2019 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Purpose: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication of antiresorptive therapy with nitrogen-containing bisphosphonates (BP). With various suggestions as to pathogenesis, the etiology of BRONJ is not sufficiently understood. Osteoclasts and their precursors, that is, macrophages, are the main target cells of BP. BP can repolarize regeneration- and healing-associated M2 macrophages towards the tissue destructive M1-type. The current study aims to elucidate differences in macrophage and osteoclast polarization in BRONJ, osteoradionecrosis (ORN) and healthy control specimens., Materials and Methods: A total of 39 jaw bone samples (18 BRONJ, 8 ORN and 13 healthy controls) were processed for immunohistochemistry to detect CD68-, CD11c- and CD163-positive cells. Macrophages and osteoclasts were distinguished on the basis of morphological differences. Samples were digitized, and the macrophage and osteoclast cell counts were quantitatively analyzed., Results: In jaw bone affected by BRONJ, a significantly increased macrophage infiltration and M1 polarization of macrophages can be seen. The density of CD68-expressing osteoclasts is significantly increased in BRONJ specimens compared to ORN and to healthy controls., Conclusions: A bisphosphonate-derived shift of macrophage polarization towards M1-polarized macrophages might impair bone tissue homeostasis and thus contribute to the pathogenesis of BRONJ. The observed increase in osteoclast density might be caused by BP-induced prolonged osteoclast survival., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: Growing evidence suggests a correlation of alternative polarization of macrophages (M2) with a bad outcome of oral cancer. Macrophage polarization plays a significant role in the progression of hyperlipidemia and atherosclerosis, being influenced from plasma cholesterol. On the other hand plasma lipids have been studied epidemiologically as risk factors in carcinogenesis. Goal of our pilot study was the investigation of a possible association of plasma lipids with tumor outcome through their potential influence on macrophage polarization., Materials and Methods: 17 patients with small pN0 OSCC with different clinical outcome, treated operatively without postoperative R(C)T constituted our patient collective. Plasma lipids (total cholesterol and triglycerides) were studied in relation to macrophage polarization (determined through the expression of CD68, CD11c, CD163 and MRC1 antibodies) and tumor outcome., Results: Patients with pathological chronic course of either plasma cholesterol or triglycerides demonstrated an increased infiltration with alternatively polarized macrophages in their specimens. Patients with pathological chronic course of plasma cholesterol showed moreover a bad tumor outcome., Conclusion: A role of plasma lipids in the tumor outcome via alternative macrophage polarization could be assumed. A larger prospective study is needed to confirm our preliminary results., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Polarization of tumor infiltrating macrophages is associated with the prognosis of solid malignancies and correlates with the occurrence of lymph node metastases in oral squamous cell carcinomas (oscc). Early stage (T1/T2, N0) oscc are characterized by a good prognosis and can be cured by surgery. The postoperative regime usually contains no adjuvant radio-/chemotherapy. The current pilot study was conducted to elucidate whether macrophage polarization in tumor resection specimens and diagnostic biopsies of early stage oscc is associated with tumor outcome., Methods: Patients with T1/T2, N0, and R0>5mm oscc without adjuvant therapy and 3-year follow-up after tumor resection were retrospectively selected. Tissue microarrays (TMA) containing diagnostic biopsies (n=17) and tumor resection specimens (n=17) were processed for immunohistochemistry in this pilot study to detect CD68-, CD11c-, CD163- and MRC1-positive macrophages. Samples were digitized, and the expression of macrophage markers was quantitatively analyzed., Results: High infiltration of M2 polarized macrophages correlated with poor tumor outcome in early stage (T1/T2, N0) oscc. This correlation was observed in tumor resection specimens, but was also observed in diagnostic biopsies. M2 macrophage polarization in biopsies - but not in tumor resection samples - correlated with high scores in tumor grading., Conclusion: Macrophage polarization in early stage oscc is a potential prognostic marker for tumor outcome. The correlation of M2 polarized macrophages with tumor outcome can already be detected in the initial biopsies. Furthermore, M2 polarization of macrophages in biopsies is associated with an increased dedifferentiation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Microsurgical tissue transfer represents a standard technique for reconstruction in craniomaxillofacial surgery. The transferred tissue is anastomosed to vessels of varying diameters and different physiological conditions. The aim of this study was to evaluate the blood flow in free flaps at their origin and compare this with the flow after reperfusion. In 24 patients undergoing microsurgical procedures (13 radial forearm free flaps (RFFF) and 11 parascapular/scapular free flaps (PSFF)), blood flow was evaluated by intraoperative fluorescence angiography after flap raising and again after reperfusion in the neck area (Flow800, Carl Zeiss AG, Oberkochen, Germany). Flow is expressed by the blood flow index (BFI), maximum intensity (MaxInt) and half-time to MaxInt (t1/2) and was measured in the flap pedicle itself, as well as in the supplying vessels. Following anastomosis of the free flaps in the head and neck area, both the arterial and the venous BFI and MaxInt significantly increased, whereas t1/2 decreased significantly. There was no significant difference in the perfusion parameters between RFFF and PSFF. Intraoperative fluorescence angiography is a reliable method for assessing the perfusion of free microvascular flaps. In the head and neck area, free flaps undergo a significant increase in perfusion but show no differences between varying flap types., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to compare autologous bone (AB), bovine bone (BB), and equine bone (EB) blocks with regard to de novo bone formation, connective tissue, and residual bone substitute material portions in a standardized defect animal model., Material and Methods: In the frontal skull of 20 pigs, 106 standardized cylindrical "critical size defects" were prepared. Defects were randomly filled with AB, BB, and EB blocks. After a healing period of 30 and 60 days, de novo bone formation, residual bone substitute material, and connective tissue portion was assessed by means of histomorphometry (Toluidine blue O staining). Mann-Whitney U-tests were used to evaluate differences between the groups., Results: The de novo bone formation was significantly higher in the AB group in comparison to the xenogeneic groups (p < 0.05). After 30 days, EB showed significantly (p < 0.05) more newly formed bone compared to the BB group. The soft tissue formation was significantly higher in the BB and EB group. Defects augmented with BB showed significantly (p < 0.05) higher portions of bone substitute materials compared to sides augmented with EB after 30 days., Conclusion: In the extra-oral model, AB blocks were superior concerning de novo bone formation. No clinical advantages of EB blocks could be observed., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: In solid malignancies the influence of immunological parameters - especially of macrophages - on invasiveness, metastatic potential and prognosis has been shown. There are no studies quantitatively analysing the macrophage polarization in oral squamous cell carcinoma (oscc). The aim of this study was to correlate macrophage polarization in the epithelial and stromal compartment of oscc with histopathologic parameters., Methods: T1 and T2 oscc samples (n = 34) were used. Automated immunohistochemical staining detected CD68, CD11c, CD163 and MRC1 positive cells. All samples were completely digitalized using whole slide imaging and the number of stained cells per area was assessed quantitatively., Results: Primary tumours with lymphogenic metastasis (N+) showed a significantly (p < 0.05) increased count of CD68, CD11c, CD163 and MRC1 positive cells in the epithelial fraction compared to N0 tumours. The ratio of CD163 positive cells (M2 macrophages) to CD68 positive cells (M1 and M2 macrophages) was significantly (p < 0.05) increased in N+ tumours., Conclusion: An increased macrophage infiltration and an increased M2 polarization in primary oral squamous cell carcinomas with lymphogenic metastasis was shown. Macrophages that migrated into the epithelial tumour fraction seem to be of special biological importance. The results indicate a central role of macrophages in the progression of oscc., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The aetiology of anti-resorptive agent-induced osteonecrosis of the jaw (ARONJ) is still under debate. Clinical and genetic risk factors are currently being investigated to help understand its pathogenesis. This case-control study analysed a large number of cancer patients (n = 230) under therapy with intravenous bisphosphonates, half of which were diagnosed with ARONJ. Multiple myeloma, greater patient age and the use of more than one bisphosphonate were identified as clinical risk factors on logistic regression analysis. In addition, 204 patients were genotyped for HLA-DRB1 and DQB1 and the allele frequencies were compared between ARONJ (n = 94) and unaffected cancer patients (n = 110). For the HLA class II alleles, a strong increase in the frequency of DRB1*15, DQB1*06:02, DRB1*01 and DQB1*05:01 was observed in the ARONJ group. These results were reinforced on analysis of the respective haplotypes, with DRB1*15-DQB1*06:02 being significantly associated with the development of ARONJ (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.3-5.0). The presence of at least one of the haplotypes DRB1*15-DQB1*06:02 and DRB1*01-DQB1*05:01 was highly associated with the development of ARONJ (OR 3.0; 95% CI 1.7-5.5). The data in this study of a large number of cancer patients receiving intravenous bisphosphonates suggest that MHC class II polymorphisms represent genetic risk factors for the development of ARONJ. This result supports recent findings that inflammation and infection might play an important role in the pathogenesis of ARONJ., (Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

In the present paper we report the oral findings of a patient who was diagnosed with hyperoxaluria. Hyperoxalurias can basically be classified as primary and secondary, with the first being inborn errors of metabolism and the second a result of excessive oxalate intake. Primary hyperoxalurias form a rare group of metabolic diseases that are inherited in the autosomal recessive fashion. The affected genes code for specific hepatic enzymes that are involved in glyoxylate metabolism and their deficiency results in overproduction of oxalate. Two different types are described: Primary hyperoxaluria type I results from a deficiency of peroxisomal enzyme alanine-glyoxylate aminotransferase and the more rare type II from a deficiency of cytosolic enzyme D-glycerate dehydrogenase. Since oxalate is primarily excreted through the kidneys, abnormally high concentration of oxalate in the urine occurs. This can in turn result in recurrent kidney stones and parenchymal renal damage and end-stage renal disease (ESRD). Inability to further excrete oxalate through the kidneys leads to its deposition in various organs (oxalosis). Several oral findings have been described in patients with oxalosis, most important of whose are bone resorption in the jaws, external root resorption and rapidly progressive dental mobility, as well as dental pain associated with deposition of oxalate in the dentine and the pulp., (Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: Impaired vascularization in the etiopathology of aminobisphosphonate-associated osteonecrosis of the jaw (BONJ) is assumed, but evidence is lacking. This immunohistochemical study differentiated vascularization and angiogenesis in BONJ-adjacent mucoperiosteal tissue., Study Design: Twenty BONJ (after zoledronate treatment) and 20 control mucoperiosteal tissue samples were processed with an autostaining-based alkaline phosphatase-antialkaline phosphatase staining kit. Vascularization was assessed by CD31 staining and angiogenesis-related neovessels by CD105 staining. The ratio of stained capillary area to total area of visible field was assessed. Statistics included Bonferroni adjustment., Results: CD31-stained microvessels were detected in each section and CD105-stained neovessels in each control. BONJ-adjacent mucoperiosteal tissue showed significantly fewer CD105-positive vessels in capillary areas (P < .05) than control samples. CD31-stained capillary area was not significantly reduced in mucoperiosteal BONJ-samples., Conclusions: Angiogenesis is impaired in BONJ-related mucoperiosteal tissue, but vascularization remains unaffected. Vessel remodeling and neovessel formation is delayed in BONJ, resulting in impaired tissue regeneration of bisphosphonate-exposed oral mucosa., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Purpose: Treatment of facial paralysis by muscular neurotization resulted in ectopic ossification in 1 of 134 cases in this department. That patient suffering from Moebius syndrome (MS) is presented. Reviewing the literature concerning MS, Hox genes and bone morphogenetic protein dysregulation, a pathogenesis of ossification in MS is suggested., Patient: The MS patient exhibited a congenital facial nerve palsy, which was treated by muscular neurotization (Lexer-Rosenthal). Because of postoperative ossification of scarred areas, osteotomy of the processus muscularis and mobilization of the masseter muscle was performed. Nevertheless, further ossification occurred at the interface between the mandible and zygoma and in two masticatory muscles. So, the construction of a neoarthrosis became necessary. Three years later, the iatrogenic bone defect had reossified despite of an active opening therapy., Conclusions: Ectopic ossification after muscular neurotization seems to be restricted to patients with MS and is triggered by trauma. Molecular pathogenesis: facial malformations in MS are caused by disturbances in embryonic patterning. Failure in the development of the second pharyngeal arch leads to a spatial BMP-4 dysregulation responsible for ossification after wounding of muscle fascia. Therefore, surgical rehabilitation of facial function by muscular neurotization is contra indicated in MS patients.

Background: Overexpression of inflammatory cytokines interleukin 1-beta (IL-1beta), transforming growth factor beta-1 (TGF-beta1), and vascular endothelial growth factor (VEGF) may cause healing impairment following implant insertion, jeopardizing success especially in patients previously irradiated. Limited data is available regarding expression pattern of inflammatory cytokines in peri-implant soft tissue caused by the surgical intervention itself., Study Design: This study examined 21 patients receiving dental implants. Biopsies of peri-implant tissue were harvested at re-entry 4 months after initial surgery. Eight patients underwent probing of untreated mucosa. Three groups were created (group 1: regular peri-implant mucosa; group 2: patients with irradiated peri-implant mucosa, radiation treatment due to oral squamous cell cancer; group 3: control). Immunohistochemical staining was performed for TGFss1, IL-1ss, and VEGF., Results: Following the placement of dental implants (group 1 vs group 3) a significant increase (P > .05) in TGF-beta1, IL-1beta, and VEGF expression in the peri-implant mucosa was demonstrated. No alteration of this distinct pattern was found for previously irradiated tissue (group 1 vs. group 2)., Conclusions: The study highlights the fundamental involvement of TGF-beta1, IL-1beta, and VEGF during the regeneration of peri-implant soft tissue structures. The use of extended interim solutions may be one clinical implication of these prolonged tissue remodeling processes.

Objective: This prospective animal study examined the de novo bone formation following application of deproteinized bovine bone matrix (DBBM) with or without autogenous bone (AB) to osseous defects., Study Design: Defects of defined size were created in the frontal skull of domestic pigs and filled with DBBM alone (group A) and DBBM+25%AB (group B). De novo bone formation was analyzed qualitatively and quantitatively at 9 different times (0.5, 1, 2, 3, 4, 6, 8, 12, 26 weeks) by means of light microscopy, microradiography, and statistical analysis., Results: Histological analysis indicated sufficient osseointegration of DBBM in both groups. Microradiography demonstrated a significant increase of bone formation in group B after 6 weeks (P = .0159) and 8 weeks (P = .0317)., Conclusion: The addition of 25%AB to DBBM results in accelerated de novo bone formation in osseous defects. This effect is likely caused by osteoinductive properties of cellular elements transplanted with the autogenous bone.

This in vivo study compared the regenerative processes within defined defects of the porcine skull after delivery of a porous algae-derived hydroxyapatite (adHA), a similar, experimental adHA carrying the cell binding peptide P-15, used solely and in combination with 25% autogenous bone (AB). Particulated AB served as a control group. During an observation period of 26 weeks, microradiography and histology were performed at four specific times. Significantly higher mineralization rates (p=0.008) were found 4 weeks after application of the bioactive material in combination with AB. At 12 weeks there was a significantly higher mineralization (p=0.036) following the application of the bioactive form alone. This study showed significantly higher mineralization after use of a P-15 bioactivated material at early stages. Thus, it can be concluded that the application of the P-15 sequence to an hydroxyapatite accelerates the process of early bone formation, whereas no long-term effect was traced.