Implant surface modifications and their impact on osseointegration and peri-implant diseases through epigenetic changes: A scoping review.

Dental implant surfaces and their unique properties can interact with the surrounding oral tissues through epigenetic cues. The present scoping review provides current perspectives on surface modifications of dental implants, their impact on the osseointegration process, and the interaction between implant surface properties and epigenetics, also in peri-implant diseases. Findings of this review demonstrate the impact of innovative surface treatments on the epigenetic mechanisms of cells, showing promising results in the early stages of osseointegration. Dental implant surfaces with properties of hydrophilicity, nanotexturization, multifunctional coatings, and incorporated drug-release systems have demonstrated favorable outcomes for early bone adhesion, increased antibacterial features, and improved osseointegration. The interaction between modified surface morphologies, different chemical surface energies, and/or release of molecules within the oral tissues has been shown to influence epigenetic mechanisms of the surrounding tissues caused by a physical-chemical interaction. Epigenetic changes around dental implants in the state of health and disease are different. In conclusion, emerging approaches in surface modifications for dental implants functionalized with epigenetics have great potential with a significant impact on modulating bone healing during osseointegration.

Unveiling the consequences of early human saliva contamination on membranes for guided bone regeneration.

AIMS: GBR membranes have various surface properties designed to elicit positive responses in regenerative clinical procedures; dental clinicians attempt to employ techniques to prevent the direct interaction of contaminated oral fluids with these biomaterials. However, saliva is uninterruptedly exhibited in oral surgical procedures applying GBR membranes, suggesting a persistent interaction with biomaterials and the surrounding oral tissues. This fundamental study aimed to investigate potential alterations in the physical, chemical, and key biological properties of membranes for guided bone regeneration (GBR) caused by isolated early interaction with human saliva. METHODS: A reproducible step-by-step protocol for collecting and interacting human saliva with membranes was developed. Subsequently, membranes were evaluated for their physicochemical properties, protein quantification, DNA, and 16S rRNA levels viability of two different cell lines at 1 and 7 days, and ALP activity. Non-interacted membranes and pure saliva of donors were applied as controls. RESULTS: Qualitative morphological alterations were noticed; DNA extraction and 16S quantification revealed significantly higher values. Furthermore, the viability of HGF-1 and MC3T3-E1 cells was significantly (p < .05) reduced following saliva interaction with biodegradable membranes. Saliva contamination did not prejudice PTFE membranes significantly in any biological assay. CONCLUSIONS: These outcomes demonstrated a susceptible response of biodegradable membranes to isolated early human saliva interaction, suggesting impairment of structural morphology, reduced viability to HGF-1 and MC3T3-E1, and higher absorption/adherence of DNA/16S rRNA. As a result, clinical oral procedures may need corresponding refinements.

Histological and radiological outcome after horizontal guided bone regeneration with bovine bone mineral alone or in combination with bone in edentulous atrophic maxilla: A randomized controlled trial.

OBJECTIVE: To assess the radiological and histological outcome after horizontal guided bone regeneration (GBR) with deproteinized bovine bone mineral (DBBM) alone or in combination with particulate autogenous bone (PAB). MATERIALS AND METHODS: Eighteen edentulous patients with an alveolar ridge of ≤4 mm were included in this split-mouth randomized controlled trial. Horizontal GBR with a graft composition of 100% DBBM (100:0) on one side and 90% DBBM and 10% PAB (90:10) on the other side were conducted in all patients. Cone beam computed tomography (CBCT) was obtained preoperatively, immediately postoperative, and after 10 months of healing. Width and volumetric changes in the alveolar process were measured on CBCT. Implants were placed after 10 months of graft healing where biopsies were obtained for histomorphometrical evaluation. RESULTS: The gained widths were 4.9 (±2.4) mm (100:0) and 4.5 (±2.0) mm (90:10) at 3 mm from the top of the crest, and 5.6 (±1.3) mm (100:0) and 4.6 (±2.1) mm (90:10) at 6 mm from the top of the crest. The mean volumetric reductions were 32.8% (±23.8) (100:0) and 38.2% (±23.2) (90:10). Histomorphometry revealed that mean percentages of bone were 50.8% (±10.7) (100:0) and 46.4% (±11.3) (90:10), DBBM were 31.6% (±12.6) (100:0) and 35.4% (±14.8) (90:10), and non-mineralized tissue were 17.6% (±11.7; 100:0) and 18.2% (±18.2) (90:10). No significant differences were evident between in any evaluated parameters. CONCLUSIONS: There were no additional effects of adding PAB to DBBM regarding bone formation, width changes, or volumetric changes after 10 months of graft healing.

Adverse effects of sterilization processes on the fundamental topographic properties of modified dental implant surfaces.

The employ of sterilization processes are essential to investigate biomaterials aiming for experimental, preclinical, or clinical applications with biological tissues. However, responsive surface properties of biomaterials may be susceptible to sterilization processes, compromising important physio-chemical characteristics. For that reason, this in vitro study aimed to investigate the effects of three different processes for sterilization (humid heat under pressure, UVC-light exposure, and Gamma irradiation) on the major topographical properties of implant surfaces applied to dental bone-anchored implants and/or implant-abutments. Three groups of implant surfaces were developed: a smooth machined surface, a micro-texturized surface, and a hydrophilic micro-texturized surface. The implants were sterilized with three methodologies and characterized regarding surface morphology, elemental surface composition, roughness parameters, wettability characteristics, and compared to the samples as-developed. Surface morphology and roughness parameters were not modified by any of the sterilization processes applied. On the other hand, hydrophilic implants were negatively affected by autoclaving. After package opening, hydrophilic features showed to be sensible to atmospheric air exposition independently of the sterilization process performed. Our findings revealed significant chemical changes on the implant surfaces caused by autoclaving and UVC exposure; additionally, the results showed the importance of selecting an appropriate sterilization method when investigating hydrophilic implants so as not to generate imprecise outcomes.

Guided bone regeneration in implant dentistry: Basic principle, progress over 35 years, and recent research activities.

Bone augmentation procedures are frequent today in implant patients, since an implant should be circumferentially anchored in bone at completion of bone healing to have a good long-term stability. The best documented surgical technique to achieve this goal is guided bone regeneration (GBR) utilizing barrier membranes in combination with bone fillers. This clinical review paper reflects 35 years of development and progress with GBR. In the 1990s, GBR was developed by defining the indications for GBR, examining various barrier membranes, bone grafts, and bone substitutes. Complications were identified and reduced by modifications of the surgical technique. Today, the selection criteria for various surgical approaches are much better understood, in particular, in post-extraction implant placement. In the majority of patients, biodegradable collagen membranes are used, mainly for horizontal bone augmentation, whereas bioinert PTFE membranes are preferred for vertical ridge augmentation. The leading surgeons are using a composite graft with autogenous bone chips to accelerate bone formation, in combination with a low-substitution bone filer to better maintain the augmented bone volume over time. In addition, major efforts have been made since the millenium change to reduce surgical trauma and patient morbidity as much as possible. At the end, some open questions related to GBR are discussed.

Effect of peri-implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures: Consensus report of group 2 of the SEPA/DGI/OF workshop.

OBJECTIVES: The aim of this study was to comprehensively assess the literature in terms of the effect of peri-implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures to increase the mucosal thickness with autogenous grafts or soft tissue substitutes. MATERIAL AND METHODS: Two systematic reviews (SR) were performed prior to the consensus meeting to assess the following questions. Review 1, focused question: In systemically healthy patients with an implant-supported fixed prosthesis, what is the influence of thin as compared to thick peri-implant mucosa on esthetic outcomes? Review 2, focused question 1: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of connective tissue graft (CTG), as compared to absence of a soft tissue grafting procedure, in terms of gain in peri-implant soft tissue thickness (STT) reported by randomized controlled clinical trials (RCTs) or controlled clinical trials (CCTs)? Review 2, focused question 2: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of CTG, as compared to soft tissue substitutes, in terms of gain in peri-implant STT reported by RCTs or CCTs? The outcomes of the two SRs, the consensus statements, the clinical implications, and the research recommendations were discussed and subsequently approved at the consensus meeting during the group and plenary sessions. CONCLUSIONS: There was a tendency of superior esthetic outcomes in the presence of a thick mucosa. The connective tissue graft remains the standard of care in terms of increasing mucosa thickness.

The Impact of Early Saliva Interaction on Dental Implants and Biomaterials for Oral Regeneration: An Overview.

The presence of saliva in the oral environment is relevant for several essential health processes. However, the noncontrolled early saliva interaction with biomaterials manufactured for oral rehabilitation may generate alterations in the superficial properties causing negative biological outcomes. Therefore, the present review aimed to provide a compilation of all possible physical-chemical-biological changes caused by the early saliva interaction in dental implants and materials for oral regeneration. Dental implants, bone substitutes and membranes in dentistry possess different properties focused on improving the healing process when in contact with oral tissues. The early saliva interaction was shown to impair some positive features present in biomaterials related to quick cellular adhesion and proliferation, such as surface hydrophilicity, cellular viability and antibacterial properties. Moreover, biomaterials that interacted with contaminated saliva containing specific bacteria demonstrated favorable conditions for increased bacterial metabolism. Additionally, the quantity of investigations associating biomaterials with early saliva interaction is still scarce in the current literature and requires clarification to prevent clinical failures. Therefore, clinically, controlling saliva exposure to sites involving the application of biomaterials must be prioritized in order to reduce impairment in important biomaterial properties developed for rapid healing.

Radiographic changes in height and volume after lateral GBR procedures with different ratios of deproteinized bovine bone mineral and autogenous bone at different time points. An experimental study.

OBJECTIVE: Estimate changes in augmentation height and volume after lateral guided bone regeneration (GBR) augmentation with different ratios of deproteinized bovine bone mineral (DBBM) and particulate autogenous bone (PAB) and autogenous bone block (ABB), at different time points. MATERIAL AND METHODS: Twenty-four minipigs were randomly allocated into three healing periods. Lateral augmentation in 96 sites with standardized quantity of graft material was performed with different ratios of DBBM and PAB (50:50, 75:25, and 100:0) and ABB in combination with DBBM, covered by a collagen membrane. Changes in augmentation height and volume were assessed on CT volumes acquired 10, 20, and 30 weeks after surgery. RESULTS: Reduction in bone augmentation height was as follows: 50:50-1.7 mm (-33.1%), 75:25-1.8 mm (-37.8%), 100:0-1.7 mm (-35.8%), and ABB - 0.2 mm (-3.7%), after 30 weeks. The augmentation height was significantly better preserved with ABB compared to 50:50, 75:25, and 100:0, while no significant difference was present among particulate grafts. No significant difference in volumetric reduction was found among 50:50, 75:25, 100:0 and ABB after 30 weeks, while 100:0 presented significant less reduction compared to 50:50, 75:25 and ABB after 10 and 20 weeks. CONCLUSIONS: Augmentation height following GBR was better preserved with ABB covered with DBBM. Addition of PAB to DBBM did not affect the changes in height of the graft. The volumetric stability seems to be comparable for ABB covered by DBBM and all particulate grafts after 30 weeks. However, DBBM alone revealed significant less volume reduction in the early healing phase.

Histological and histomorphometrical outcome after lateral guided bone regeneration augmentation of the mandible with different ratios of deproteinized bovine bone mineral and autogenous bone. A preclinical in vivo study.

OBJECTIVE: To test the hypotheses of no differences in (I) percentage of bone (POB), non-mineralized tissue (NMT), and deproteinized bovine bone mineral (DBBM), and (II) ingrowth of mineralized bone after lateral guided bone regeneration (GBR) augmentation of the mandible with different ratios of DBBM and particulate autogenous bone (PAB) at different time points. MATERIAL AND METHODS: Twenty-four minipigs were randomly allocated into three groups. Lateral augmentation in 96 sites (4 in each animal) was performed unilaterally with a standardized quantity of grafting material in each animal with different ratios of DBBM and PAB (50:50, 75:25, 100:0) and autogenous bone block in combination with DBBM and covered with a collagen membrane. The percentage of different tissues in the graft and ingrowth of mineralized bone was assessed by histomorphometrical and histological analyses after 10, 20, and 30 weeks, respectively. RESULTS: The POB was 54% (50:50), 50% (75:25), and 48% (100:0) after 10 weeks, 60% (50:50), 61% (75:25), and 60% (100:0) after 20 weeks, and 63% (50:50), 62% (75:25), and 62% (100:0) after 30 weeks. There was no significant difference between the groups at any time points. There was a significant increase in POB and a significant decrease in NMT for 75:25 and 100:0 from 10 to 30 weeks. All ratios demonstrated a non-complete ingrowth of mineralized bone into the graft after 10 weeks and complete mineralization after 30 weeks. CONCLUSION: Within the limitations of the present study, it seems like addition of autogenous bone to DBBM for LRA did not affect the bone formation nor graft incorporation after 10-30 weeks of healing. However, a prolonged healing time seems to result in an increased POB for all ratios.

Expression of MicroRNAs in Periodontal and Peri-Implant Diseases: A Systematic Review and Meta-Analysis.

AIM: The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker. MATERIALS AND METHODS: Human and animal studies were included when evaluating expression of miRNAs between health and different forms/stages of diseases, in which microarray and/or real-time polymerase chain reaction (RT-PCR) was carried out to detect fold changes in gene expression. After full-text analysis, 43 articles were considered for a qualitative assessment, and 16 miRNAs were selected to perform meta-analysis. RESULTS: Based on human studies, results showed an overall upregulation of most of the evaluated miRNAs in periodontitis, with miRNA-142-3p and miRNA-146a being the most conclusive on both microarray and RT-PCR values and potentially serving as diagnostic biomarkers for disease activity. Conversely, miR-155 was the only miRNA revealing a statistically significant difference (SSD) (p < 0.05*) in experimental periodontitis models from RT-PCR values. Scarce scientific evidence is available from peri-implant diseases, however, most explored miRNAs in peri-implantitis were downregulated except for miR-145. CONCLUSIONS: Although our results revealed that a distinct differential expression of specific miRNAs can be noted between the state of health and disease, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases. MeSH Terms: periodontitis, peri-implantitis, epigenomics, microarray analysis, real-time polymerase chain reaction, microRNAs. CLINICAL RELEVANCE: Scientific background: Although most research identified different expression levels of miRNAs in periodontal and peri-implant diseases compared to their counterparts, their actual role in the pathogenesis of these conditions remains unclear. Therefore, we aimed to present a systematic review and meta-analysis on the expression patterns of miRNAs in periodontitis and peri-implantitis, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker. PRINCIPAL FINDINGS: In periodontitis-related studies, miRNA-142-3p and miRNA-146a were the most conclusive on both microarray and RT-PCR values. Scarce scientific evidence is available from peri-implant diseases. PRACTICAL IMPLICATIONS: Both miRNA-142-3p and miRNA-146a might serve as future diagnostic biomarkers for disease activity in periodontitis. Yet, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases.

The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration-A Review.

The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put forward the epigenetic mechanisms as a promising strategy in implant surface functionalization and modification of biomaterials, to promote better osseointegration and bone regeneration, and could be applicable for alveolar bone regeneration and osseointegration in the future. Materials and Methods: Electronic and manual searches of the literature in PubMed, MEDLINE, and EMBASE were conducted, using a specific search strategy limited to publications in the last 5 years to identify preclinical studies in order to address the following focused questions: (i) Which, if any, are the epigenetic mechanisms used to functionalize implant surfaces to achieve better osseointegration? (ii) Which, if any, are the epigenetic mechanisms used to functionalize biomaterials to achieve better tissue regeneration? Findings from several studies have emphasized the role of miRNAs in functionalizing implants surfaces and biomaterials to promote osseointegration and bone regeneration, respectively. However, there are scarce data on the role of DNA methylation and histone modifications for these specific applications, despite being commonly applied in cancer research. Studies over the past few years have demonstrated that biomaterials are immunomodulatory rather than inert materials. In this context, epigenetics can act as next generation of advanced treatment tools for future regenerative techniques. Yet, there is a need to evaluate the efficacy/cost effectiveness of these techniques in comparison to current standards of care.

Hearing outcome after myringoplasty in Sweden: A nationwide registry-based cohort study.

OBJECTIVES: To present hearing results after successful primary myringoplasty surgeries registered in the Swedish Quality Registry for Myringoplasty and to evaluate the chance of hearing improvement and the risk of hearing loss. DESIGN: A retrospective nationwide cohort study based on prospectively collected registry data between 2002 and 2012. SETTINGS: Registry data from secondary and tertiary hospitals performing myringoplasty. PARTICIPANTS: Patients with healed tympanic membrane after primary myringoplasty surgery performed from 2002 to 2012 in Sweden. MAIN OUTCOME MEASURES: Postoperative hearing results, hearing gain and air-bone gap (ABG). RESULTS: In 2226 myringoplasties, air conduction audiograms were recorded, and the average preoperative pure tone average (PTA4 ) of the group was 28.5 dB, which improved postoperatively to 19.6 dB with an average of 8.8 dB improvement. Bone conduction was measured for 1476 procedures. Closure of the ABG to 10 dB or less was achieved in 51% of the ears and to less than 20 dB in 89% of the ears. Sixty-one percent of patients with preoperatively deteriorated hearing experienced improved hearing, but 3% of all patients experienced deteriorated hearing. After the surgery, 93% of the patients were satisfied. CONCLUSIONS: Hearing results after successful myringoplasty surgery are often favourable, but although the tympanic membrane is healed, hearing improvement is not guaranteed, and hearing deterioration can also occur.

Barrier membranes: More than the barrier effect?

AIM: To review the knowledge on the mechanisms controlling membrane-host interactions in guided bone regeneration (GBR) and investigate the possible role of GBR membranes as bioactive compartments in addition to their established role as barriers. MATERIALS AND METHODS: A narrative review was utilized based on in vitro, in vivo and available clinical studies on the cellular and molecular mechanisms underlying GBR and the possible bioactive role of membranes. RESULTS: Emerging data demonstrate that the membrane contributes bioactively to the regeneration of underlying defects. The cellular and molecular activities in the membrane are intimately linked to the promoted bone regeneration in the underlying defect. Along with the native bioactivity of GBR membranes, incorporating growth factors and cells in membranes or with graft materials may augment the regenerative processes in underlying defects. CONCLUSION: In parallel with its barrier function, the membrane plays an active role in hosting and modulating the molecular activities of the membrane-associated cells during GBR. The biological events in the membrane are linked to the bone regenerative and remodelling processes in the underlying defect. Furthermore, the bone-promoting environments in the two compartments can likely be boosted by strategies targeting both material aspects of the membrane and host tissue responses.

Biomaterials and regenerative technologies used in bone regeneration in the craniomaxillofacial region: Consensus report of group 2 of the 15th European Workshop on Periodontology on Bone Regeneration.

BACKGROUND AND AIMS: To review the regenerative technologies used in bone regeneration: bone grafts, barrier membranes, bioactive factors and cell therapies. MATERIAL AND METHODS: Four background review publications served to elaborate this consensus report. RESULTS AND CONCLUSIONS: Biomaterials used as bone grafts must meet specific requirements: biocompatibility, porosity, osteoconductivity, osteoinductivity, surface properties, biodegradability, mechanical properties, angiogenicity, handling and manufacturing processes. Currently used biomaterials have demonstrated advantages and limitations based on the fulfilment of these requirements. Similarly, membranes for guided bone regeneration (GBR) must fulfil specific properties and potential biological mechanisms to improve their clinical applicability. Pre-clinical and clinical studies have evaluated the added effect of bone morphogenetic proteins (mainly BMP-2) and autologous platelet concentrates (APCs) when used as bioactive agents to enhance bone regeneration. Three main approaches using cell therapies to enhance bone regeneration have been evaluated: (a) "minimally manipulated" whole tissue fractions; (b) ex vivo expanded "uncommitted" stem/progenitor cells; and (c) ex vivo expanded "committed" bone-/periosteum-derived cells. Based on the evidence from clinical trials, transplantation of cells, most commonly whole bone marrow aspirates (BMA) or bone marrow aspirate concentrations (BMAC), in combination with biomaterial scaffolds has demonstrated an additional effect in sinus augmentation and horizontal ridge augmentation, and comparable bone regeneration to autogenous bone in alveolar cleft repair.

Histomorphometric analyses of area fraction of different ratios of Bio-Oss® and bone prior to grafting procedures - An in vitro study to demonstrate a baseline.

OBJECTIVE: The objective of this study was to estimate the area fraction of different ratios of Bio-Oss® and bone, prior to grafting in an in vitro model to demonstrate a histomorphometric baseline. METHODS: Bio-Oss® particles were mixed with autogenous bone from pig jaw in three different ratios (50:50, 80:20 and 100:0) and packed in rice paper in a standardized procedure. Histomorphometric analyses were performed in 25 specimens and 74 regions of interest. The area percentage of Bio-Oss® , bone, and non-mineralized tissue (NMT) were calculated. Results were reported as mean values and 95% confidence interval (CI). RESULTS: The mean area fraction of Bio-Oss® was 20.6% (CI: 18.2-23) in the 50:50 mixture, 33.6% (CI: 29.7-37.6) in the 80:20 mixture, and 43.4% (CI: 40.5-46.3) in the 100:0 mixture. The mean area fraction of NMT was 60.5% (CI: 57.9-63.1) in the 50:50 mixture, 59.6% (CI: 56.4-62.7) in the 80:20 mixture, and 56.6% (CI: 53.7-59.5) in the 100:0 mixture. The mean area fraction of bone was 18.9% (CI: 16.9-20.9) in the 50:50 mixture and 6.8% (CI: 5-8.6) in the 80:20 mixture. CONCLUSION: There is a great difference in the clinically estimated percentage and the histomorphometrically evaluated percentage of Bio-Oss® at baseline, prior to grafting. The area fraction of different tissues presented in this study may be beneficial as guidance for histomorphometrical baseline calculations when different mixtures of Bio-Oss® and autogenous bone are used as grafting materials.

Tissue dynamics and regenerative outcome in two resorbable non-cross-linked collagen membranes for guided bone regeneration: A preclinical molecular and histological study in vivo.

OBJECTIVES: To investigate the molecular and structural patterns of bone healing during guided bone regeneration (GBR), comparing two resorbable non-cross-linked collagen membranes. MATERIALS AND METHODS: Trabecular bone defects in rat femurs were filled with deproteinized bovine bone (DBB) and covered with either a membrane comprising collagen and elastin (CXP) or collagen (BG). Samples were harvested after 3 and 21 days for histology/histomorphometry and gene expression analysis. Gene expression analysis was performed on the membrane (at 3 days) and the underlying defect compartment (at 3 and 21 days). RESULTS: At the total defect level, no differences in bone area percentage were found between the CXP and BG. When evaluating the central area of the defect, a higher percentage of de novo bone formation was seen for the CXP membrane (34.9%) compared to BG (15.5%) at 21 days (p = .01). Gene expression analysis revealed higher expression of bone morphogenetic protein-2 (Bmp2) in the membrane compartment at 3 days in the BG group. By contrast, higher Bmp2 expression was found in the defect compartment treated with the CXP membrane, both at 3 and 21 days. A significant temporal increase (from 3 to 21 days) in the remodeling activity, cathepsin K (Catk) and calcitonin receptor (Calcr), was found in the CXP group. Molecular analysis demonstrated expression of several growth factors and cytokines in the membrane compartment irrespective of the membrane type. Bmp2 expression in the membrane correlated positively with Bmp2 expression in the defect, whereas fibroblast growth factor-2 (Fgf2) expression in the membrane correlated positively with inflammatory cytokines, tumor necrosis factor-alpha (Tnfa) and interleukin-6 (Il6) in the defect. CONCLUSIONS: The results provide histological and molecular evidence that different resorbable collagen membranes contribute differently to the GBR healing process. In the BG group, bone formation was primarily localized to the peripheral part of the defect. By contrast, the CXP group demonstrated significantly higher de novo bone formation in the central portion of the defect. This increase in bone formation was reflected by triggered expression of potent osteogenic growth factor, Bmp2, in the defect. These findings suggest that the CXP membrane may have a more active role in regulating the bone healing dynamics.

Guided bone regeneration: materials and biological mechanisms revisited.

Guided bone regeneration (GBR) is commonly used in combination with the installment of titanium implants. The application of a membrane to exclude non-osteogenic tissues from interfering with bone regeneration is a key principle of GBR. Membrane materials possess a number of properties which are amenable to modification. A large number of membranes have been introduced for experimental and clinical verification. This prompts the need for an update on membrane properties and the biological outcomes, as well as a critical assessment of the biological mechanisms governing bone regeneration in defects covered by membranes. The relevant literature for this narrative review was assessed after a MEDLINE/PubMed database search. Experimental data suggest that different modifications of the physicochemical and mechanical properties of membranes may promote bone regeneration. Nevertheless, the precise role of membrane porosities for the barrier function of GBR membranes still awaits elucidation. Novel experimental findings also suggest an active role of the membrane compartment per se in promoting the regenerative processes in the underlying defect during GBR, instead of being purely a passive barrier. The optimization of membrane materials by systematically addressing both the barrier and the bioactive properties is an important strategy in this field of research.

Demineralized Xenogenic Dentin and Autogenous Bone as Onlay Grafts to Rabbit Tibia.

PURPOSE: The present study was undertaken to evaluate the healing pattern of xenogenic demineralized dentin onlay grafts in comparison with autogenous bone grafts to the rabbit tibia. MATERIAL AND METHODS: Eight 6-month-old New Zealand male rabbits were used in the experiments. Standardized sized dentin blocks from human premolars and similar autogenous bone blocks harvested from tibia were grafted as onlay blocks on each tibia (n = 8 × 2). All animals were killed after a healing period of 12 weeks. RESULTS: Healing was uneventful for all animals. In general, both the dentin and bone block grafts were fused to the bone, resorbed, and replaced by bone and connective tissue to a varying degree. Both types of grafts were still present after 12 weeks, on an average to approximately one third of the original sizes. Resorption cavities could be seen in the dentin with bone formation. Zones of osseous replacement resorption of the dentin could be noted. In both graft types, higher rate of bone formation was seen at the interface between graft and recipient site. CONCLUSION: Demineralized xenogenic dentin onlay grafts showed similar resorption characteristics as autogenous bone onlay grafts, being resorbed in a similar rate during 12 weeks. New bone formation occurred mainly in terms of replacement resorption in the interface between dentin/bone graft and native bone.

Comparative maxillary bone-defect healing by calcium-sulphate or deproteinized bovine bone particles and extra cellular matrix membranes in a guided bone regeneration setting: an experimental study in rabbits.

OBJECTIVES: The aim of this study was to histologically compare the dynamics of bone healing response between calcium sulphate (CaS) and deproteinized bovine bone mineral (DBBM) particles in guided bone regeneration utilizing an extracellular matrix membrane (ECM) as barrier. MATERIALS AND METHODS: Eighteen rabbits were used in thisstudy. 5 × 5 mm defects were created in the edentulous space between the incisors and molars in the maxilla. The CaS and DBBM particles were placed in the defects, with or without the placement of a membrane by means of random selection. Healing was evaluated at 2, 4 and 8 weeks by histology. RESULTS: A total resorption of the CaS material was seen already at 2 weeks. Only minor resorption could be seen of the DBBM particles. The CaS group showed significantly more bone regeneration at all three healing periods compared to the DBBM group. The addition of an ECM membrane demonstrated significant additional effect on bone regeneration. The CaS group showed significant increased amounts of blood vessels compared to the DBBM group. CONCLUSIONS: Thisstudy showed that CaS in combination with an ECM membrane provided synergistic effects on bone regeneration, seemingly due to stimulating angiogenesis in the early healing process.

Bone tissue modelling and remodelling following guided bone regeneration in combination with biphasic calcium phosphate materials presenting different microporosity.

OBJECTIVES: The aim of this study was to investigate bone regeneration following application of a novel biphasic calcium phosphate (BCP I) composed of microstructured granules of 90% ß-tricalcium phosphate (ß-TCP)/10% hydroxyapatite (HA) compared to BCP non-microstructured biphasic calcium phosphate with a composite of 60% hydroxyapatite/40% ß-TCP (BCP II) and a deproteinized bovine bone mineral (DBBM) at surgically created defects in the mandible of minipigs in a combined approach with guided bone regeneration (GBR). MATERIAL AND METHODS: Sixteen minipigs were used for the study. Lower premolars P2, P3, P4 and first molar M1 were extracted. Following 3 months of healing, two defects with a width and depth of 7 mm were created bilaterally in the mandible. The different grafting materials were randomly placed in the created defects and covered by means of a collagen membrane. After 3 and 8 weeks, biopsies were sampled. All specimens were evaluated with descriptive histology and histomorphometric evaluations complemented by micro-CT scan analysis. RESULTS: All three biomaterials presented with higher bone volume at 8 weeks compared to 3 weeks (P < 0.0442). BCP I and DBBM demonstrated a significant higher amount of bone formation compared to BCP II at 8 weeks (P < 0.0328). BCP I also demonstrated a significant higher percentage of remaining graft volume compared to the other test groups both at 3 and 8 weeks (P < 0.0001 to P < 0.0003). Congruently, defects containing BCP I showed a significant higher amount of mineralized tissue compared to the other groups. CONCLUSIONS: All the three test materials performed well with regard to bone formation at 8 weeks. BCP I showed significant higher amounts of newly formed bone despite a higher remaining graft volume compared to the other groups. With regard to the regenerative outcome, all the three materials can be recommended for clinical use.