Characterization of circulating molecules and activities in plasma of patients after allogeneic and autologous intraoral bone grafting procedures: a prospective randomized controlled clinical trial in humans.

BACKGROUND: The objective was to assess whether intraoral bone augmentation procedures have an impact on the patient's plasma levels of circulating nucleic acids, exosomes, miRNA levels and caspase activities. The null hypothesis was tested, that no significant differences between the two groups will be found. METHODS: In this prospective randomized controlled clinical trial 35 systemically healthy non-smoking participants were randomly allocated using sealed envelopes by a blinded clinician not involved in the clinical setting. Plasma samples were collected preoperatively and 3 times postoperatively (immediately, 5 weeks and 4 months postoperatively). The test group consisted of twenty-five patients who received allogeneic bone grafting material and the control group of ten patients who received autologous bone grafts. Levels of cell-free DNA (cfDNA) and microRNAs (miR-21, miR-27a, miR-218) were quantified by real-time PCR, caspase activities and exosome concentrations were determined by ELISA. RESULTS: Statistical evaluation reveled a significantly higher exosome level before surgery (p = 0.013) and the first postsurgical sample (p = 0.017) in the control group compared to the test group. The levels of miR-27a and miR-218 significantly differed between the plasma samples before surgery and after surgery in both groups. The levels of miR-21 only significantly differed between the pre- and postsurgical plasma samples in the test group, but not in the control group. All patients completed the study, no adverse events were recorded. CONCLUSIONS: Our data show the diagnostic potential of the plasma levels of miR-27a, miR-218 and miR-21 in detecting changes in bone metabolism after alveolar bone augmentation. Our very promising results indicate that there might be a high diagnostic potential in evaluating the plasma levels of the before mentioned miRNAs in order to detect bone resorption activities before they become clinically relevant. Trial registration Ethical commission of the Ärztekammer Hamburg, Germany (PV5211) on 11/03/2016 as well as by the German Registry of Clinical Studies (DRKS 00,013,010) on 30/07/2018 ( http://apps.who.int/trialsearch/ ).

Characterization of immunologically detectable T-cell sensitization, Immunohistochemical detection of pro-inflammatory cytokines, and clinical parameters of patients after allogeneic intraoral bone grafting procedures: a prospective randomized controlled clinical trial in humans.

BACKGROUND: The null hypotheses were tested that intraoral bone augmentation using two different allogeneic materials has no impact on the patient's blood levels of material-specific lymphocytes and on the immunohistochemical detection of pro-inflammatory cytokines IL-1α, IL1ß and TNF-α and T-cell markers CD4, CD8 in biopsies of the test groups. METHODS: In this prospective RCT, 60 systemically healthy participants were randomly assigned to two allogeneic test groups (1: Maxgraft®, freeze-dried, multiple donors, and 2: Puros®, solvent-dehydrated, single donor) and an autologous control group (10 patients). Plasma samples were collected pre-(T1) and postoperatively (2 weeks (T2) and 4 months (T3)). The Lymphocyte Transformation Test (LTT) was used for analyzing levels of transformed lymphocytes for type IV immune reactions by 3H-thymidine activity. Bone biopsies were harvested at T3 and immunohistochemically analyzed for IL-1α, IL1ß, TNF-α, CD4, CD8 and correlated with the immunological and clinical findings. RESULTS: A statistically significant difference between the tested materials was observed for LTT measurements at T3 (p = 0.033). Furthermore, three groups were identified: Group A (LTT negative T1-T3, n = 48), group B (LTT positive T1-T3, n = 7), group C (developing positive LTT at T2, n = 5). A highly significant elevation of IL-1α, IL1ß, TNF-α in patients of group C (p = 0.0001) and a significant elevation of CD4+ cells in patients of group B (p = 0.005) was shown. CONCLUSION: Our data show that following allogeneic bone grafting, local and systemic immunological reactions can be detected in some patients. These findings were statistically significant for the timepoint T3 between the tested materials as well as for the groups B and C correlated with group A for both tested materials. Therefore, the null hypotheses were rejected. A preoperative compatibility test for allogeneic materials in order to improve patient safety and the predictability of these materials would be desirable. TRIAL REGISTRATION: Ethical commission of the Ärztekammer Hamburg, Germany (PV5211) as well as by the German Registry of Clinical Studies (DRKS00013010) on 30/07/2018 ( http://apps.who.int/trialsearch/ ).

The prevalence of orofacial injuries in judo: A cross-sectional study.

BACKGROUND/AIMS: Judo is a popular martial art with a high risk of injury. Notwithstanding this risk, mouthguards were not allowed until June 2018. The aim of this study was to measure the prevalence of traumatic injuries in judo with a particular focus on dental and lip injuries. A further aim was to assess the influences of increased overjet and wearing fixed orthodontic appliances. MATERIAL AND METHODS: Judokas (n = 382) from two judo clubs in Bern, Switzerland, were interviewed with a standardized questionnaire. RESULTS: About two thirds had suffered at least one traumatic injury with a high number of limb injuries (n = 1054), followed by face injuries (n = 855) and spine, torso, occiput or neck injuries (n = 84). Among the face injuries, 562 lip injuries were recorded. A significantly higher number of lip injuries were found for judokas who wore fixed orthodontic appliances compared to judokas who never wore such appliances. Forty-seven dental trauma incidents during judo were recorded. During both judo and leisure time, 161 dental trauma incidents were recorded. Individuals with lip incompetence and increased overjet showed the highest number of dental injuries ( x ¯ = 0.815; SD = 0.622), which differed in statistically significant ways from the number of dental injuries in individuals with lip incompetence and normal or reduced overjet ( x ¯ = 0.278; SD = 0.461). For individuals with no lip incompetence, no difference between the sub-group with an increased overjet and the sub-group with a normal or reduced overjet could be found. Nobody in the study population was wearing a mouthguard, and the acceptance of mouthguards was low (9.7%). CONCLUSION: It is important to increase the awareness of the recent authorization of mouthguards and to promote their acceptance among judokas. The combination of increased overjet and lip incompetence was more relevant for the dental trauma risk than an increased overjet alone.

Characterization of circulating DNA in plasma of patients after allogeneic bone grafting.

OBJECTIVES: Cell-free DNA (cfDNA) harboring mutations has been found in patients with diseases. Experimental studies have shown that cfDNA can be transmitted, leading to transformations in the host. In the present study, we evaluated whether bone allograft material contains cfDNA and whether this foreign cfDNA can be released into the patient's blood circulation. MATERIALS AND METHODS: Plasma samples were collected preoperatively and postoperatively on the same day, at 5 weeks, and 4 months from 25 women who received bone allograft material (test group) from male donors and from 10 women who were treated with autologous graft (control group, only pre- and postoperative samples were collected). DNA was quantified and characterized in bone material and plasma samples by quantitative PCR with primers specific for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Y chromosome and gel electrophoresis. DNA in bone material was digested by different concentrations of DNase I. RESULTS: We detected between 1 and 1.8 µg cfDNA fragments at a length around 601 base pairs (bp) and smaller in each 100 mg allograft. Treatment of the allograft with DNase I completely degraded the longer but not the shorter DNA 90-bp fragments. Y-DNA was not detected in the patients' bloodstream at any time during the treatment and follow-up, but elevated levels of circulating cfDNA could be measured immediately postoperatively. CONCLUSIONS: Our results suggest that a transmission of DNA from allografts used for alveolar ridge reconstruction in humans is unlikely. The observed increase in circulating cfDNA in allograft and autograft patients immediately postoperatively may be elicited by the surgical procedure. CLINICAL RELEVANCE: The results support the safety of allograft materials. The results suggest that human allograft materials seem not to release DNA into the blood since we did not measure Y-DNA with our technique.

A 3-year prospective randomized clinical trial of alveolar bone crest response and clinical parameters through 1, 2, and 3 years of clinical function of implants placed 4 months after alveolar ridge preservation using two different allogeneic bone-grafting materials.

PURPOSE: The aim of this study was to longitudinally evaluate changes in alveolar bone crest (ABC) levels and differences in resorption rates (RR) between the tested grafting materials following alveolar ridge preservation (ARP) after tooth extraction after 1, 2, and 3 years (T1-T8) of clinical function. METHODS: Patients were randomly assigned to two different bone allografts (group 1 maxgraft®, group 2 Puros®) for ARP. Non-restorable teeth were minimal traumatically extracted. Sockets were augmented with the tested materials and covered with a pericardium membrane. After 4 months of healing, 36 implants were placed and sites were clinically and radiographically monitored in the mesial (ABC-M), the distal (ABC-D, T1-T8), the bucco-lingual (ABC-BL), buccal (ABC-B) and oral (ABC-O) aspect (T1-T4). RESULTS: Changes in (ABC-M), (ABC-D), (ABC-BL), (ABC-B), and (ABC-O) levels showed statistically highly significant differences between T1 and T2 for both bone allografts (p < 0.001). Changes at the ABC-M and ABC-BL levels between T2 and T3 of group 1 showed a statistically significant difference (p < 0.001). Both groups achieved and maintained increased ABC levels without statistically significant differences throughout the monitoring periods of 1-3 years (T6-T8) of clinical function. No failures or adverse events were observed. CONCLUSIONS: To the best of our knowledge, this study is within its limitations the first study to directly compare ABC-changes and differences in RR of two different allogeneic grafting materials for a period of 3 years after ARP. It was demonstrated to be, despite significant differences in RR, a successful method of preserving increased ABC levels through 1, 2, and 3 years of clinical function. Trial registration DRKS00013010, registered 07/30/2018, http://apps.who.int/trialsearch.

The use of plasma rich in growth factors (PRGF) in guided tissue regeneration and guided bone regeneration. A review of histological, immunohistochemical, histomorphometrical, radiological and clinical results in humans.

BACKGROUND: Modern surgeries have advanced toward personalized minimal-invasive treatments with a high rate of clinical healing that facilitates the regeneration of tissues. One of the leading approaches to deliver endogenous plasma- and platelet-derived growth factors is the plasma rich in growth factors (PRGF). This narrative review determines the effects of using PRGF in different oral surgical procedures including alveolar ridge augmentation, socket preservation, sinus floor augmentation and periodontal regeneration. METHODS: For this narrative review, a literature search was conducted using PubMed and Researchgate. A combination of the following text words was used to maximize search specificity and sensitivity: "platelet-rich plasma", "PRP", "PRGF", "Platelet-rich growth factor", "socket preservation", "Extraction", "infra-bony pockets", "sinus floor augmentation", "randomized clinical controlled trials", "Alveolar osteitis", "Periodontal regeneration", "guided bone regeneration", "guided tissue regeneration". RESULTS: Investigations have generally agreed that PRGF can promote and accelerate the healing process. PRGF optimizes the patient's quality of life by reducing pain, swelling and inflammation rate and also accelerates regeneration of soft tissue and bone tissue regeneration as well. CONCLUSIONS: There is increasing evidence to support the use of PRGF in oral surgical procedures in order to improve the healing processes of the oral soft and hard tissues.

Histological and immunohistochemical comparison of two different allogeneic bone grafting materials for alveolar ridge reconstruction: A prospective randomized trial in humans.

BACKGROUND: Preclinical studies have hypothesized a possible immunological reponse to allogeneic materials due to detection of remnants of potential immunogenic molecules. However, their impact on integration, bone remodeling and immunological reaction after the augmentation procedure is largely unknown and a direct correlation of analytical data and evaluation of human biopsies is missing. PURPOSE: The present study aimed to compare two commercially available allogeneic materials regarding their content of cellular remnants as well as the bone remodeling, and integration and potential immunologic reactions on a histological and immunohistochemical level, integrating also in vitro analytical evaluation of the specific batches that were used clinically. MATERIALS AND METHODS: Twenty patients were randomly assigned to treatment with Maxgraft or Puros for lateral ridge augmentation in a two-stage surgery. After a mean healing period of 5 months, implants were placed and biopsies were taken for histological, immunhistochemical, and histomorphometrical evaluation regarding bone remodeling and inflammation, protein concentrations in vitro and the presence of MHC molecules of the same batches used clinically. RESULTS: No differences in clinical outcome, histological, immunohistochemical, and in vitro protein analysis between the two bone grafting materials were observed. Active bone remodeling, amount of newly formed bone, and residual grafting material was independent of the materials used, but varied between subjects. MHC1 residues were not detected in any sample. CONCLUSIONS: Within the limitations of this study, both tested materials yielded equivalent results in terms of clinical outcome, new bone formation, and lack of immunological potential on a histological and immunohistochemical level.

Improved guided bone regeneration by combined application of unmodified, fresh autologous adipose derived regenerative cells and plasma rich in growth factors: A first-in-human case report and literature review.

BACKGROUND: Novel strategies are needed for improving guided bone regeneration (GBR) in oral surgery prior to implant placement, particularly in maxillary sinus augmentation (GBR-MSA) and in lateral alveolar ridge augmentation (LRA). This study tested the hypothesis that the combination of freshly isolated, unmodified autologous adipose-derived regenerative cells (UA-ADRCs), fraction 2 of plasma rich in growth factors (PRGF-2) and an osteoinductive scaffold (OIS) (UA-ADRC/PRGF-2/OIS) is superior to the combination of PRGF-2 and the same OIS alone (PRGF-2/OIS) in GBR-MSA/LRA. CASE SUMMARY: A 79-year-old patient was treated with a bilateral external sinus lift procedure as well as a bilateral lateral alveolar ridge augmentation. GBR-MSA/LRA was performed with UA-ADRC/PRGF-2/OIS on the right side, and with PRGF-2/OIS on the left side. Biopsies were collected at 6 wk and 34 wk after GBR-MSA/LRA. At the latter time point implants were placed. Radiographs (32 mo follow-up time) demonstrated excellent bone healing. No radiological or histological signs of inflammation were observed. Detailed histologic, histomorphometric, and immunohistochemical analysis of the biopsies evidenced that UA-ADRC/PRGF-2/OIS resulted in better and faster bone regeneration than PRGF-2/OIS. CONCLUSION: GBR-MSA with UA-ADRCs, PRGF-2, and an OIS shows effectiveness without adverse effects.

Transreplantation: An alternative for periodontally hopeless teeth.

The periodontal therapy of severely damaged teeth that have advanced bone loss, a significant degree of mobility, and often tooth migration and elongation, frequently exposes the dental clinician to difficult decisions regarding the appropriate therapy for the patient. Extensive rehabilitation, with the replacement of periodontally hopeless teeth, has biologic, prognostic, and financial limitations. A possible alternative in such cases is the transreplantation of periodontally hopeless teeth. Ankylosis of the tooth is induced by appropriate extraoral pretreatment and thus the mobility disappears and the alveolar bone is reformed. This little-known technique is described step by step, with reference to a clinical case.

Immediate implant placement and restoration in the anterior maxilla: a tissue-related approach. Observations at 12 months after loading.

Retreatment of a failed prosthetic rehabilitation often presents a challenge for both clinicians and patients. Endosseous dental implants are a commonly used treatment modality to restore esthetics and function. Implant protocols differ considerably with regard to healing time and the number of surgical procedures required. This has a great impact on the treatment strategy used and therefore significantly influences patient acceptance. The present case report describes the rehabilitation of a failed maxillary anterior fixed partial denture using immediate implant placement and provisionalization. This tissue-related, esthetically driven treatment strategy is comprehensively presented with a follow-up of 12 months postoperatively.