Platelet-rich fibrin for rehydration and pre-vascularization of an acellular, collagen membrane of porcine origin.

OBJECTIVES: Pre-vascularization of the collagen membranes with autologous platelet concentrates is a standard procedure in oral and maxillofacial surgery. This study analyzed the possible interaction of an acellular collagen membrane of porcine origin (NM) with platelet-rich fibrin (PRF) regarding its rehydration protocol with differences in pH values and effect on angiogenesis. MATERIALS AND METHODS: NM was analyzed alone and combined with solid PRF by plotting or co-culturing with injectable PRF. Different media (venous blood, buffer solution with a fixed pH value of 7, saline solution, and injectable PRF) were used to analyze the influence on pH value during rehydration. Chorion allantois membrane assay (CAM) was applied to check pro-angiogenic effects after 24, 48, and 72 h, followed by immunohistochemical analysis. RESULTS: Rehydration in injectable PRF showed acidity over time (p < 0.05). A definite pro-angiogenic effect of NM alone was found regarding neo-vessel formation supported by the respective light microscopically analysis without significant differences to PRF alone (p > 0.005). This pro-angiogenic effect could not be exaggerated when NM was combined with liquid/solid PRF (each p > 0.005). CONCLUSIONS: Rehydration with liquid PRF of the collagen membrane results in acidity compared to a saline solution or patient's blood. The significant pro-angiogenic potential of the membrane alone resulted in enhanced neo-vessel formation that could not be optimized with the addition of PRF. CLINICAL RELEVANCE STATEMENT: Using injectable PRF for rehydration protocol of the collagen membrane leads to acidosis that can ultimately optimize wound healing. Differences in the physio-mechanical interplay of collagen matrices and autologous platelet concentrates must result in clinical algorithms if pre-vascularization can maximize outcomes.

Cytotoxic impact of nicotine products on periodontal ligament cells.

OBJECTIVES: The primary objective of this in vitro experiment was an assessment of proliferative capacity, metabolic activity, and potential cellular detriment of human periodontal ligament cells (hPDL) exposed to cigarette smoke (CS), electronic cigarette vapor (eCV), and heated tobacco product aerosol (HTP), or air (control). MATERIALS AND METHODS: Using a CAD/CAM-designed exposition chamber, hPDL were exposed to CS, eCV, HTP, or air (control) based on the Health Canada Intense Smoking Regime. Cell proliferation, metabolic activity, and cellular detriment were assessed at various time points. RESULTS: Compared to the control, hPDL exposed to CS exhibited significantly decreased cell numbers at all time points. HTP exposure led to reduced cell numbers 48 h and 72 h post-exposure, while eCV-exposed cells showed no significant decrease. The metabolic activity of eCV-treated hPDL was slightly reduced at 7 h but recovered at 24 h and 48 h. In contrast, CS-treated cells exhibited significantly decreased metabolic activity at 24 h and 48 h, and HTP-exposed cells showed a significant decrease after 48 h. Flow cytometry indicated both apoptotic and necrotic cell death following CS exposure, with necrotic cell death being more pronounced. CONCLUSIONS: eCV and HTP demonstrated comparatively reduced detrimental effects on hPDL compared to CS. CLINICAL RELEVANCE: The findings suggest that conventional cigarette smoke poses a substantial risk to periodontal health by significantly impairing cell proliferation and metabolic activity. However, alternatives such as eCV and HTP may offer a comparatively reduced risk.

Clinical insights into traumatic injury of the inferior alveolar and lingual nerves: a comprehensive approach from diagnosis to therapeutic interventions.

OBJECTIVES: This scoping review explores the risk and management of traumatic injuries to the inferior alveolar and lingual nerves during mandibular dental procedures. Emphasizing the significance of diagnostic tools, the review amalgamates existing knowledge to offer a comprehensive overview. MATERIALS AND METHODS: A literature search across PubMed, Embase, and Cochrane Library informed the analysis. RESULTS: Traumatic injuries often lead to hypo-/anesthesia and neuropathic pain, impacting individuals psychologically and socially. Diagnosis involves thorough anamnesis, clinical-neurological evaluations, and radiographic imaging. Severity varies, allowing for conservative or surgical interventions. Immediate action is recommended for reversible causes, while surgical therapies like decompression, readaptation, or reconstruction yield favorable outcomes. Conservative management, utilizing topical anesthesia, capsaicin, and systemic medications (tricyclic antidepressants, antipsychotics, and serotonin-norepinephrine-reuptake-inhibitors), proves effective for neuropathic pain. CONCLUSIONS: Traumatic nerve injuries, though common in dental surgery, often go unrecorded. Despite lacking a definitive diagnostic gold standard, a meticulous examination of the injury and subsequent impairments is crucial. CLINICAL RELEVANCE: Tailoring treatment to each case's characteristics is essential, recognizing the absence of a universal solution. This approach aims to optimize outcomes, restore functionality, and improve the quality of life for affected individuals.

DIGITAL DENTISTRY AND ITS IMPACT ON ORAL HEALTH-RELATED QUALITY OF LIFE.

Over the past 50 years, digitization has gradually taken root in dentistry, starting with computer tomography in the 1970s. The most disruptive events in digital dentistry were the introduction of digital workflow and computer-aided manufacturing, which made new procedures and materials available for dental use. While the conventional lab-based workflow requires light or chemical curing under inconsistent and suboptimal conditions, computer-aided manufacturing allows for industrial-grade material, ensuring consistently high material quality. In addition, many other innovative, less disruptive, but relevant approaches have been developed in digital dentistry. These will have or already impact prevention, diagnosis, and therapy, thus impacting patients' oral health and, consequently, their oral health-related quality of life. Both software and hardware approaches attempt to maintain, restore, or optimize a patient's perceived oral health. This article outlines innovations in dentistry and their potential impact on patients' oral health-related quality of life in prevention and therapy. Furthermore, possible future developments and their potential implications are characterized.

Bone reconstruction of extensive maxillomandibular defects in adults.

Reconstruction of significant maxillomandibular defects is a challenge that has been much discussed over the last few decades. Fundamental principles were developed decades ago (bone bed viability, graft immobilization). Clinical decision-making criteria are highly relevant, including local/systemic factors and incision designs, the choice of material, grafting technique, and donor site morbidity. Stabilizing particulated grafts for defined defects-that is, via meshes or shells-might allow significant horizontal and vertical augmentation; the alternatives are onlay and inlay techniques. More significant defects might require extra orally harvested autologous bone blocks. The anterior iliac crest is often used for nonvascularized augmentation, whereas more extensive defects often require microvascular reconstruction. In those cases, the free fibula flap has become the standard of care. The development of alternatives is still ongoing (i.e., alloplastic reconstruction, zygomatic implants, obturators, distraction osteogenesis). Especially for these complex procedures, three-dimensional planning tools enable facilitated planning and a surgical workflow.

Platelet-rich fibrin ensures hemostasis after single-tooth removal under factor Xa inhibitors - a clinical prospective randomized split-mouth study.

OBJECTIVES: In this prospective, double-blinded, randomized split-mouth study, the local hemostatic effect of platelet-rich fibrin (PRF) inserted into the extraction socket in patients taking factor Xa (FXa) inhibitors (apixaban, rivaroxaban, edoxaban) was compared to a hemostatic gelatine sponge (GS) as the "therapeutic gold standard" without withdrawal of oral anticoagulant therapy. MATERIALS AND METHODS: Single-tooth extraction was conducted under local anesthesia in n = 21 patients using a split-mouth design (42 teeth). Using a double-blind approach, the extraction socket on one side of the jaw was filled with PRF and on the other with a GS. Bleeding was assessed immediately after surgery, in 30 min, 1 h, 1.5 h, and on follow-up appointments in 24 h and on the 7th day. RESULTS: In 67% of cases, mild postoperative oozing could be stopped 30-90 min after tooth extraction via gauze pressure without any delayed bleeding. Concerning bleeding events, there was no difference among the PRF and GS groups and no significant difference among rivaroxaban, apixaban, and edoxaban (all p > 0.15). CONCLUSION: PRF and GS are reliable hemostatic methods in postextraction sockets of patients taking FXa inhibitors. CLINICAL RELEVANCE: Consequently, there is no need to discontinue FXa inhibitors because of a single-tooth removal, eliminating the risk of thrombus formation.

The impact of electronic and conventional cigarettes on periodontal health-a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis examined the effects of electronic cigarettes on periodontal health compared to conventional cigarette smoke and a non-smoking population. MATERIALS AND METHODS: MEDLINE, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were screened for literature. Eligibility criteria included clinical studies published between 2006 and 2022 that compare e-cigarettes and conventional cigarettes on periodontal health (bleeding on probing (BoP), plaque index (PI), probing depth (PD), attachment loss (AL), marginal bone loss (MBL), tooth loss, molecular inflammation markers, salivary flow rate). Meta-regression analysis was used to examine the influence of moderator variables. RESULTS: Sixteen studies were found to be eligible for qualitative synthesis. Individual analyses showed that cigarette smokers had significantly higher PI, PD, AL, and MBL and increased concentrations of proinflammatory mediators than e-cigarette users and non-smokers. Meta-analysis revealed a 0.33-fold lower chance for BoP in e-cigarette users compared to smokers (p = 0.03), whereby meta-regression failed to detect any effects regarding the age of users and frequency of smoking. A 0.01-fold decreased chance for positive BoP in e-cigarette users compared with non-smokers was seen (p < 0.01). CONCLUSIONS: The current findings suggest that that e-cigarette use might be considered a healthier alternative to cigarette smoking concerning periodontal health. Even so, harmful effects of electronic nicotine delivery system (ENDS) usage on periodontal health were seen as well. However, a definitive decision on this research question remains elusive due to the absence of randomized controlled trials. CLINICAL RELEVANCE: Electronic cigarettes, marketed as a safer alternative to traditional cigarettes, are becoming increasingly popular. Evidence on the use of electronic cigarettes as a cessation aid and its beneficial impact compared to cigarette smoke remains inconclusive, so the analysis conducted in this review addresses a recent question of high clinical relevance.

Evaluation of Medication-Related Osteonecrosis of the Jaw (MRONJ) in Terms of Staging and Treatment Strategies by Dental Students at Different Educational Levels.

Background: The role of medication-related osteonecrosis of the jaw (MRONJ) as a dento-maxillo-facial pathology is becoming increasingly important due to its growing prevalence. The success of preventive and therapeutic measures relies mainly on the dentist's ability to correctly diagnose the disease. Methods: The aim of this study was to evaluate the skills of dental students of different educational levels in choosing the correct stage, diagnostics, and treatment option for MRONJ based on clinical and radiographic imaging (panoramic radiograph, CBCT). The study was designed as a cross-sectional cohort study. Twenty dental students were asked to complete a questionnaire in their third and fifth year of studies in which they had to correctly stage the disease, choose the radiological diagnostics and recommend the treatment. The control group contained experienced oral and maxillofacial surgeons. Results: With an overall performance of 59% (third year: 145.2/248 points; fifth year: 145.3/248 points), no statistically significant difference between the educational levels could be observed. The classification based on CBCT imaging was significantly more often correct compared to panoramic radiographs (p < 0.001). Conclusions: This study highlights students' lack of knowledge in staging, diagnostics, and treatment of MRONJ, even though the CBCT positively affected decision-making. No significant increase in knowledge could be confirmed through clinical education. This study highlights the need for students to catch up on MRONJ diagnostics and treatment planning. Further expansion of teaching in this disease's context and X-ray diagnostics is needed.

Long-term results in three-dimensional, complex bone augmentation procedures with customized titanium meshes.

OBJECTIVES: Complex, three-dimensional bony defects still represent challenging situations in routine implant dentistry. The aim of this study was to evaluate implant survival in customized bone regeneration using a patient-specific titanium mesh. MATERIAL AND METHODS: Patients (n = 21, implants 36) who had obtained an augmentation procedure with patient-specific titanium mesh were examined after 5.7 ± 0.38 years. Survival rate, clinical parameters for periimplantitis (Bleeding on Probing [BOP] and suppuration), and radiographic examination were evaluated. Peri-implant marginal bone loss (MBL) was calculated by using an image assessment program. Additionally, the influence of various factors on treatment outcomes such as periodontitis, smoking, professional maintenance, or diabetes was assessed as well as the impact on quality of life applying the Oral Health Impact Profile (OHIP). RESULTS: The implant survival rate was 97%, with one implant loss in the lower jaw. At the end of the observation period, MBL showed mesial 0.13 ± 1.84 mm and distal -0.13 ± 1.73 mm. The lower jaw showed significant more MBL mesial compared with the upper jaw (p = .034, cluster-adjusted). Periodontitis was significantly associated with MBL mesial and distal (p < .05). Positive BOP (four implants) was significantly associated with MBL mesial (p = .0031) and distal (p = .0018). MBL was significantly associated with suppuration mesial (p < .0001) and distal (p < .0001). CONCLUSIONS: CBR® results in high implant survival rate and stabilized augmented marginal bone after follow-up of minimum 5 years. Periodontitis seems to play the mayor role for long-term stability indicated by BOP and suppuration.

Biomechanical evaluation of cyanoacrylate-based tissue adhesive for intraoral wound closure.

OBJECTIVES: The aim of this study was to analyze the biomechanical characteristics of a novel cyanoacrylate-based tissue adhesive (CTA) for soft-tissue closure of the (non-) tooth-bearing alveolar process and around dental implants. MATERIALS AND METHODS: Halves of porcine mandibles (n = 21) were randomly divided into three experimental intraoral wound closure groups (A-C) with three different mucoperiosteal flap types (F1-3, n = 7 each): F1, crestal incision between the last incisor and the canine with a mesial and distal vestibular relief; F2, crestal double-T-shaped incision and dental implant placement between the canine and the first premolar; and F3, trapezoidal incision on the second premolar. F1-3 were respectively closed using (A) monofil non-resorbable sutures, (B) CTA, and (C) a combination of both. Tensile strength (TS) and elasticity (E) measurements were performed for biomechanical analysis. RESULTS: In F1, CTA showed a significantly reduced TS compared to A (p < 0.001) and C (p < 0.01). In F2, an increased TS of C compared to A (p < 0.01) and B (p < 0.001) was found. Here, E was significantly increased in C compared to B (p < 0.02). In F3, TS was significantly decreased in B compared to A (p < 0.01) and C (p < 0.001). The E in group C was significantly increased compared to B (p < 0.01). CONCLUSIONS: Different biomechanical characteristics between CTA and sutures were found. CTA could be a possible alternative to sutures for intraoral wound closure in special conditions. CLINICAL RELEVANCE: A combination of both, suturing and CTA, could be a promising option in critical soft-tissue wounds requiring high functional stability and elasticity.

Effects of throat packs in upper airway surgery under intubation anesthesia: a randomized controlled trial.

INTRODUCTION: Throat packs (TP) are used in upper airway surgery to avoid accumulation and aspiration of blood, foreign bodies, and fluids. But side effects such as sore throat and TP retention have been reported and challenge the standardized use of TP. The aim of this study is to compare benefits and side effects of TP versus no TP for upper airway procedures in intubation anesthesia. MATERIAL AND METHODS: One hundred forty-eight patients with surgical interventions at the upper airway under intubation anesthesia were included. Of those, n = 74 each were treated without (A, control) and with (B) TP. Study group B was subdivided whether TP was placed by the surgeon (B1; n = 37) or by the anesthesiologist (B2; n = 37). TP-related side effects such as sore throat, foreign body sensation, hoarseness, dyspnea, difficulty of swallowing, nausea, retching, nausea, aspiration, and pneumonia as well as the influence of TP design and the applicant (surgeon or anesthetist) were analyzed. RESULTS: A significantly increased rate of difficulty of swallowing (p = 0.045), intensity of sore throat (p = 0.04), and foreign body sensation (p = 0.024) was found in group B when compared to group A. There was no correlation between hoarseness, dyspnea, nausea, retching, and TP. No case of aspiration or pneumonia was seen but one TP was accidentally forgotten in the patient. B2 showed an increased frequency of difficulty swallowing, followed by A and B1. B1 led to the highest incidence of nausea followed by the A and B2. CONCLUSION: The use of TP led to a high rate of side effects without showing the propagated advantages. CLINICAL RELEVANCE: The use of TP must be considered critically and cannot generally be recommended without specific reasons, such as high aspiration risk.

Treatment concepts of horizontally deficient ridges-A retrospective study comparing narrow-diameter implants in pristine bone with standard-diameter implants in augmented bone.

OBJECTIVES: To compare clinical and radiological outcomes of narrow-diameter implants (NDI) placed in pristine bone to standard-diameter implants placed in combination with horizontal bone augmentation procedures (SDI+A) for horizontally deficient alveolar ridges. MATERIAL AND METHODS: For this retrospective study, the outcome of 597 NDI (∅ 3.3 mm, 272 patients), inserted in pristine bone, were compared with 180 SDI (∅ 4.1 mm, 83 patients), inserted in combination with horizontal augmentation procedures. Oral health-related quality of life was assessed in patients available for recall. RESULTS: After a mean follow-up of 37.6 ± 40 months for the NDI and of 42.4 ± 49 months for the SDI+A, survival rates were 96.1% for NDI and 95.6% for SDI+A. Cumulative 5-year and 10-year implant survival rates were 94.3% and 92.2% for the NDI group and 97.0% and 88.3% for the SDI+A group, indicating no significant difference (p = .89). According to the criteria of Buser et al., an implant success rate of 84.3% was obtained for the NDI and an implant success rate of 81.3% for the SDI+A (p = .79). Regarding oral health-related quality of life, a similar and high patient satisfaction could be observed in both groups. CONCLUSIONS: NDI without augmentation procedures showed a similar clinical outcome as SDI in combination with augmentation procedures after a follow-up of more than 3 years. Therefore, NDI might be a reasonable alternative in cases of horizontal bone atrophy (no clinical trial registration as patient inclusion started 2003).

Complications or rather side effects? Quantification of patient satisfaction and complications after orthognathic surgery-a retrospective, cross-sectional long-term analysis.

OBJECTIVES: The aim of this clinical analysis was to evaluate intraoperative and early postoperative complications as well as late findings and the overall patient satisfaction following orthognathic surgery. MATERIALS AND METHODS: In a retrospective, cross-sectional study, 119 patients after orthognathic surgery were included. Surgical approaches were single bilateral sagittal split osteotomy (BSSO (n = 52)), single LeFort-I osteotomy (n = 5) and bimaxillary osteotomy (LeFort-I + BSSO (n = 62)). Intraoperative and early (0-4 weeks postoperative) complications were investigated retrospectively (n = 119), whereas late findings and quality of life were assessed via clinical follow-up and survey (mean: 59 months postoperative) on 48 patients. RESULTS: Bad split (n = 4/114) was the most common intraoperative complication followed by one case of severe bleeding. Regarding early postoperative complications, temporary damage of the inferior alveolar nerve after BSSO was most common (n = 33/114), followed by facial nerve dysfunction (n = 3), failed osteosynthesis (n = 2) and one case of postoperative dyspnoea. Permanent hypaesthesia of the lower lip was the most prevalent (n = 28/45(BSSO and LeFort-I + BSSO)) late finding with varying extent, followed by temporomandibular dysfunction (TMD) (n = 25/48). Skeletal relapse mostly occurred after class II treatment, followed by class III, posterior crossbite and open bite. Overall, the surgery improved the patients' self-perception (85.4%), with 60.4% of patients opting for surgery again. CONCLUSIONS: Long-term complications after orthognathic surgery occurred more frequently than commonly described in the literature, and analyses of the quality of life show the need for more comprehensive preoperative patient education. CLINICAL RELEVANCE: Hypaesthesia of the lower lip presented less as complication but rather as side effect following BSSO. As orthognathic surgery is mostly elective, preoperative patient education is of pivotal importance and should include proactive risk stratification.

Inflammation in the Human Periodontium Induces Downregulation of the α1- and ß1-Subunits of the sGC in Cementoclasts.

Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α1- and ß1-subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α1- and ß1-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α1- and ß1-subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.

Zoledronate Causes a Systemic Shift of Macrophage Polarization towards M1 In Vivo.

BACKGROUND: Immunomodulatory properties of bisphosphonates (BP) are suggested to contribute to the development of medication-associated osteonecrosis of the jaw (MRONJ). Furthermore, bisphosphonate-derived immune modulation might contribute to the anti-metastatic effect observed in breast cancer patients. Macrophages are potential candidates for the mediation of immunomodulatory effects of bisphosphonates. The study aimed to investigate the influence of bisphosphonates alone and in combination with surgical trauma on systemic macrophage polarization (M1 vs. M2) using an in vivo rat model. METHODS: A total of 120 animals were divided into four groups. Groups 2 and 4 were treated with 8 × 40 µg/kg body weight of the BP Zoledronate i.p. (week 0-7). Groups 3 and 4 were exposed to surgical trauma (week 8, tooth extraction + tibia fracture), whereas in Group 1 neither medication nor surgical trauma was applied. After 8, 10, 12 and 16 weeks, skin, lung and spleen were immunohistochemically examined for macrophage polarization via expression analysis of CD68, CD163 and iNOS using a tissue microarray (TMA). RESULTS: A significant shift of macrophage polarization towards M1 was observed in skin, spleen and lung tissue of animals, with and without surgical trauma, treated with BP when compared to those without BP application. Surgical trauma did not cause a significant increase towards M1 polarization. CONCLUSIONS: BP application leads to a systemic pro-inflammatory situation in vivo, independent of surgical trauma, as evidenced by the shift in macrophage polarization towards M1 in various somatic tissues. This provides a possible explanation for the clinically observed anti-tumor effect of bisphosphonates and might also contribute to pathogenesis of MRONJ.

Treatment Modalities of Recurrent Oral Mucosal Melanoma In Situ.

Oral mucosal melanoma (OMM) represents an extremely rare entity that is associated with a poor prognosis due to late diagnosis and early metastasis. Here, extensive surgical therapy is the therapy of choice. In contrary, for OMM in situ, the respective therapeutical recommendations are lacking. In this case report, treatment modalities of an OMM in situ of the palate, including the maxillary alveolar process, are reported. The tumor relapsed twice despite adequate surgical therapy and reconstruction. Therefore, irradiation was performed as an adjuvant therapy. At a follow-up of two years, the patient was free from recurrences.

Extracorporeal Shock Wave Stimulates Angiogenesis and Collagen Production in Facial Soft Tissue.

BACKGROUND: This study investigated the efficacy of extracorporeal shock wave (ESW) application in stimulating dermal thickness, vascularity, and collagen synthesis of facial skin in a large animal model. MATERIALS AND METHODS: The facial skin of the maxillary and mandibular areas of goats (n = 6 per group) was treated with ESWs of different intensities (0.15 and 0.45 mJ/mm2; 1000 pulses). After 4 d, histology and immunohistochemistry were used to evaluate the following: dermal thickness, total number and abundance of microvessels, amount of type 1 collagen, and α-smooth muscle actin expression. RESULTS: Dermal thickness, number and abundance of microvessels, and collagen synthesis increased after ESW application at both intensities (each P < 0.05). When comparing ESW groups, the highest collagen abundance was seen after 0.15 mJ/mm2 (P = 0.034), whereas the highest number of microvessels was detected after treatment with 0.45 mJ/mm2 (P = 0.002). CONCLUSIONS: A single-session application of focused low-energy ESWs to facial skin can increase dermal thickness by stimulating collagen production and local microcirculation. These findings commend the technique for future investigation for pretreatment of local or microvascular skin flaps to enhance tissue healing.

Cigarette smoke modulates binding of the transcription factor MZF1 to the VEGF promoter and regulates VEGF expression in dependence of genetic variation SNP 405.

BACKGROUND: Vascular endothelial growth factor (VEGF) affects carcinogenesis of the upper aerodigestive tract. Cigarette smoke (CSE) influences VEGF-gene regulation. The single nucleotide polymorphism +405 G/C (SNP +405 G/C) and the transcriptional factor (TF) myeloid zinc finger 1 (MZF1) are endogenic regulators of the VEGFpromoter as the polymorphism 405 potentially affects binding of the transcription factor MZF1. Therefore, this in vitro study analysed cancer cells of the upper aerodigestive tract after CSE incubation concerning MZF1-binding specificity and VEGF expression in dependency of VEGF polymorphism +405 G/C compared to wild type (wt). METHODS: In human alveolar epithelial-like type-II cells (A549) and oral squamous cell cancer cells (HNSCCUM-02T) SNP +405 G/C- and MZF1-dependent VEGF promoter activity and VEGF expression were analysed by qRT-PCR and Western blot after incubation with 10% CSE. Temporary knock-down of MZF1 was performed using siRNA. MZF1 binding was analysed by Co-Chromatin-Immunoprecipitation (Co-ChiP) (each test n = 3). RESULTS: We found a stronger MZF1 binding to VEGF polymorphism 405 in A549 cells (P < .05) compared to HNSCCUM-02T cells (P = .02), where MZF1 binding was reduced. MZF1 knock out reduced VEGF promoter activity in HNSCCUM-02T cells, showing the relevance of the factor for transcriptional activation of the VEGF promoter. Finally, we found that CSE increases promoter activity in both cell lines and no significant differences between the two analysed polymorphisms concerning their activating capacity. CONCLUSION: In summary, both VEGF promoter polymorphisms are similar effective in terms of transcriptional activity, and MZF1 is a transcriptional activator of VEGF promoter. Moreover, cigarette smoke increases MZF1 binding of VEGF-promoter and directly affects VEGF-gene regulation.

Calcium Phosphate-Coated Titanium Implants in the Mandible: Limitations of the in vivo Minipig Model.

INTRODUCTION: We aimed to compare implant osseointegration with calcium phosphate (CaP) surfaces and rough subtractive-treated sandblasted/acid etched surfaces (SA) in an in vivo minipig mandible model. MATERIALS AND METHODS: A total of 36 cylindrical press-fit implants with two different surfaces (CaP, n = 18; SA, n = 18) were inserted bilaterally into the mandible of 9 adult female minipigs. After 2, 4, and 8 weeks, we analyzed the cortical bone-to-implant contact (cBIC; %) and area coverage of bone-to-implant contact within representative bone chambers (aBIC; %). RESULTS: After 2 weeks, CaP implants showed no significant increase in cBIC and aBIC compared to SA (cBIC: mean 38 ± 5 vs. 16 ± 11%; aBIC: mean 21 ± 1 vs. 6 ± 9%). Two CaP implants failed to achieve osseointegration. After 4 weeks, no statistical difference between CaP and SA was seen for cBIC (mean 54 ± 15 vs. 43 ± 16%) and aBIC (mean 43 ± 28 vs. 32 ± 6). However, we excluded two implants in each group due to failure of osseointegration. After 8 weeks, we observed no significant intergroup differences (cBIC: 18 ± 9 vs. 18 ± 20%; aBIC: 13 ± 8 vs. 16 ± 9%). Again, three CaP implants and two SA implants had to be excluded due to failure of osseointegration. CONCLUSION: Due to multiple implant losses, we cannot recommend the oral mandibular minipig in vivo model for future endosseous implant research. Considering the higher rate of osseointegration failure, CaP coatings may provide an alternative to common subtractive implant surface modifications in the early phase post-insertion.

Biofunctionalization of porcine-derived collagen matrices with platelet rich fibrin: influence on angiogenesis in vitro and in vivo.

OBJECTIVES: Porcine-derived collagen matrices (CM) can be used for oral tissue regeneration, but sufficient revascularization is crucial. The aim of this study was to analyze the influence of platelet-rich fibrin (PRF) on angiogenesis of different CM in vitro and in vivo. MATERIALS AND METHODS: Three different CM (mucoderm®, jason®, collprotect®) were combined with PRF in a plotting process. Growth factor release (VEGF, TGF-ß) was measured in vitro via ELISA quantification after 1,4 and 7 days in comparison to PRF alone. In ovo yolk sac (YSM) and chorion allantois membrane (CAM) model, angiogenic potential were analyzed in vivo with light- and intravital fluorescence microscopy after 24 h, then verified with immunohistochemical staining for CD105 and αSMA. RESULTS: Highest growth factor release was seen after 24 h for all three activated membranes in comparison to the native CM (VEGF 24 h: each p < 0.05; TGF-ß: each p < 0.001) and the PRF (no significant difference). All activated membranes revealed a significantly increased angiogenic potential in vivo after 24 h (vessels per mm2: each p < 0.05; branching points per mm2: each p < 0.01; vessel density: each p < 0.05) and with immunohistochemical staining for CD105 (each p < 0.01) and αSMA (each p < 0.05). CONCLUSIONS: PRF improved the angiogenesis of CM in vitro and in vivo. CLINICAL RELEVANCE: Bio-functionalization of CM with PRF could easily implemented in the clinical pathway and may lead to advanced soft tissue healing.