Analyses of the Cellular Interactions between the Ossification of Collagen-Based Barrier Membranes and the Underlying Bone Defects.

Barrier membranes are an essential tool in guided bone Regeneration (GBR), which have been widely presumed to have a bioactive effect that is beyond their occluding and space maintenance functionalities. A standardized calvaria implantation model was applied for 2, 8, and 16 weeks on Wistar rats to test the interactions between the barrier membrane and the underlying bone defects which were filled with bovine bone substitute materials (BSM). In an effort to understand the barrier membrane's bioactivity, deeper histochemical analyses, as well as the immunohistochemical detection of macrophage subtypes (M1/M2) and vascular endothelial cells, were conducted and combined with histomorphometric and statistical approaches. The native collagen-based membrane was found to have ossified due to its potentially osteoconductive and osteogenic properties, forming a "bony shield" overlying the bone defects. Histomorphometrical evaluation revealed the resorption of the membranes and their substitution with bone matrix. The numbers of both M1- and M2-macrophages were significantly higher within the membrane compartments compared to the underlying bone defects. Thereby, M2-macrophages significantly dominated the tissue reaction within the membrane compartments. Statistically, a correlation between M2-macropahges and bone regeneration was only found at 2 weeks post implantationem, while the pro-inflammatory limb of the immune response correlated with the two processes at 8 weeks. Altogether, this study elaborates on the increasingly described correlations between barrier membranes and the underlying bone regeneration, which sheds a light on the understanding of the immunomodulatory features of biomaterials.

Suitability of R. pulmo Jellyfish-Collagen-Coated Well Plates for Cytocompatibility Analyses of Biomaterials.

Cytocompatibility analyses of new implant materials or biomaterials are not only prescribed by the Medical Device Regulation (MDR), as defined in the DIN ISO Norm 10993-5 and -12, but are also increasingly replacing animal testing. In this context, jellyfish collagen has already been established as an alternative to mammalian collagen in different cell culture conditions, but a lack of knowledge exists about its applicability for cytocompatibility analyses of biomaterials. Thus, the present study was conducted to compare well plates coated with collagen type 0 derived from Rhizostoma pulmo with plates coated with bovine and porcine collagen. The coated well plates were analysed in vitro for their cytocompatibility, according to EN ISO 10993-5/-12, using both L929 fibroblasts and MC3T3 pre-osteoblasts. Thereby, the coated well plates were compared, using established materials as positive controls and a cytotoxic material, RM-A, as a negative control. L929 cells exhibited a significantly higher viability (#### p < 0.0001), proliferation (## p < 0.01), and a lower cytotoxicity (## p < 0.01 and # p < 0.05)) in the Jellagen® group compared to the bovine and porcine collagen groups. MC3T3 cells showed similar viability and acceptable proliferation and cytotoxicity in all collagen groups. The results of the present study revealed that the coating of well plates with collagen Type 0 derived from R. pulmo leads to comparable results to the case of well plates coated with mammalian collagens. Therefore, it is fully suitable for the in vitro analyses of the cytocompatibility of biomaterials or medical devices.

The Use of Collagen-Based Materials in Bone Tissue Engineering.

Synthetic bone substitute materials (BSMs) are becoming the general trend, replacing autologous grafting for bone tissue engineering (BTE) in orthopedic research and clinical practice. As the main component of bone matrix, collagen type I has played a critical role in the construction of ideal synthetic BSMs for decades. Significant strides have been made in the field of collagen research, including the exploration of various collagen types, structures, and sources, the optimization of preparation techniques, modification technologies, and the manufacture of various collagen-based materials. However, the poor mechanical properties, fast degradation, and lack of osteoconductive activity of collagen-based materials caused inefficient bone replacement and limited their translation into clinical reality. In the area of BTE, so far, attempts have focused on the preparation of collagen-based biomimetic BSMs, along with other inorganic materials and bioactive substances. By reviewing the approved products on the market, this manuscript updates the latest applications of collagen-based materials in bone regeneration and highlights the potential for further development in the field of BTE over the next ten years.

Barrier Membranes for Guided Bone Regeneration (GBR): A Focus on Recent Advances in Collagen Membranes.

Guided bone regeneration (GBR) has become a clinically standard modality for the treatment of localized jawbone defects. Barrier membranes play an important role in this process by preventing soft tissue invasion outgoing from the mucosa and creating an underlying space to support bone growth. Different membrane types provide different biological mechanisms due to their different origins, preparation methods and structures. Among them, collagen membranes have attracted great interest due to their excellent biological properties and desired bone regeneration results to non-absorbable membranes even without a second surgery for removal. This work provides a comparative summary of common barrier membranes used in GBR, focusing on recent advances in collagen membranes and their biological mechanisms. In conclusion, the review article highlights the biological and regenerative properties of currently available barrier membranes with a particular focus on bioresorbable collagen-based materials. In addition, the advantages and disadvantages of these biomaterials are highlighted, and possible improvements for future material developments are summarized.

In Vivo Analysis of the Regeneration Capacity and Immune Response to Xenogeneic and Synthetic Bone Substitute Materials.

Although various studies have investigated differences in the tissue reaction pattern to synthetic and xenogeneic bone substitute materials (BSMs), a lack of knowledge exists regarding the classification of both materials based on the DIN ISO 10993-6 scoring system, as well as the histomorphometrical measurement of macrophage subtypes within their implantation beds. Thus, the present study was conducted to analyze in vivo responses to both xenogeneic and synthetic bone substitute granules. A standardized calvaria implantation model in Wistar rats, in combination with established scoring, histological, histopathological, and histomorphometrical methods, was conducted to analyze the influence of both biomaterials on bone regeneration and the immune response. The results showed that the application of the synthetic BSM maxresorb® induced a higher pro-inflammatory tissue response, while the xenogeneic BSM cerabone® induced a higher anti-inflammatory reaction. Additionally, comparable bone regeneration amounts were found in both study groups. Histopathological scoring revealed that the synthetic BSM exhibited non-irritant scores at all timepoints using the xenogeneic BSM as control. Overall, the results demonstrated the biocompatibility of synthetic BSM maxresorb® and support the conclusion that this material class is a suitable alternative to natural BSM, such as the analyzed xenogeneic material cerabone®, for a broad range of indications.

Lyophilized Human Bone Allograft as an Antibiotic Carrier: An In Vitro and In Vivo Study.

Background: Antibiotics delivered from implanted bone substitute materials (BSM) can potentially be used to prevent acute infections and biofilm formation, providing high concentrations of antibiotics at the surgical site without systemic toxicity. In addition, BSM should allow osteoconductivity supporting bone healing without further surgery. Promising results have been achieved using lyophilized bone allografts mixed with antibiotics. Methods: In this study specially prepared human bone allografts were evaluated as an antibiotic carrier in vitro and in vivo. The efficacy of different antibiotic-impregnated bone allografts was measured by drug release tests in vitro and in vivo and bacterial susceptibility tests using four bacterial species usually responsible for implant-associated infections. Results: The loading procedures of allograft bone substitutes with antibiotics were successful. Some of the antibiotic concentrations exceeded the MIC90 for up to 7 days in vitro and for up to 72 h in vivo. The susceptibility tests showed that S. epidermidis ATCC 12228 was the most susceptible bacterial species in comparison to the other strains tested for all antibiotic substances. Vancomycin and rifampicin showed the best results against standard and patient-isolated strains in vitro. In vivo, new bone formation was comparable in all study groups including the control group without antibiotic loading. Conclusions: Human bone allografts showed the capacity to act as customized loaded antibiotic carriers to prevent acute infections and should be considered in the management of bone infections in combination with systemic antimicrobial therapy.

Surgical treatment outcome after serial debridement of infected nonunion-A retrospective cohort study.

PURPOSE: Reported outcome after multiple staged surgical treatment of infected nonunion is scarce. We, therefore, asked: (1) What is the clinical outcome in infected nonunion patients after multiple staged revision surgery? (2) Are different pathogens evidenced after surgical treatment in patients who have undergone more or less surgeries? METHODS: All enrolled patients were surgically treated for long bone-infected nonunion between January 2010 and March 2018. Besides patients´ demographics outcome in terms of bony consolidation and major complications defined as death during inward treatment, amputation and recurrence of infection during follow-up of at least 12 months were assessed. Microbiological findings were assessed and compared between two groups with less than five versus five or more surgical revisions. RESULTS: Bone consolidation was achieved in 86% of the patients while complications such as femoral or transtibial amputation, recurrence of infection or even death during inpatient treatment could be evidenced in six patients (14%). In patients who underwent multiple-stage surgery for five or more times, germ changes and repeated germ detection was more common than in patients with less surgeries. CONCLUSIONS: Surgical treatment of infected nonunions poses a high burden on the patients with major complications occurring in about 14% of the patients using a multiple staged treatment concept. Future prospective studies comparing outcomes after limited with multiple staged revision surgeries are necessary.

Polymicrobial infections and microbial patterns in infected nonunions - a descriptive analysis of 42 cases.

BACKGROUND: Frequencies of polymicrobial infection and pathogens evidenced in course of infected nonunion treatment are largely unknown. Therefore, this study aims at investigating microbial patterns in infected nonunions. METHODS: Surgically treated patients with long bone infected nonunion admitted between January 2010 and March 2018 were included in the study. Microbiological culture and polymerase-chain-reaction results of tissue samples of initial and follow-up revision surgeries were assessed and compared with patient and treatment characteristics. RESULTS: Forty two patients with a mean age of 53.9 ± 17.7 years were included. In six patients (14.3%) polymicrobial infection was evident. A change of pathogens evidenced in course of the treatment occurred in 21 patients (50%). In 16 patients (38.1%) previously detected bacteria could be determined by microbial testing after further revision surgery. Staphylococcus aureus was most often detected (n = 34, 30.6%), followed by Enterococcus spp. (n = 25, 22.5%) and Staphylococcus epidermidis (n = 18, 16.2%). Five Staphylococcus aureus were resistant to methicillin (MRSA). In patients without polymicrobial infection or further germ detection in course of the treatment, 86.4% of the infections were due to Staphylococcus spp.. Infections due to Streptococcus spp. and gram-negative bacteria were only present in patients with polymicrobial infection and germ-change in course of the treatment. CONCLUSION: A low rate of polymicrobial infections was evidenced in the present study. Germ-change often occurs in course of revision surgeries. Prospective studies with more sensitive diagnostic tools are necessary to elucidate the therapeutical relevance of microbiological testing results for surgical as well as medical treatment in infected nonunions.

In Vitro and In Vivo Biocompatibility Studies of a Cast and Coated Titanium Alloy.

The biocompatibility of a cast porous and with a calcium titanate reaction layer functionalized titanium alloy (Ti-6Al-7Nb) was tested by means of cell culture, and a small (rat) and large animal (sheep) model. The uncoated titanium material served as a control. In-vitro tests included the validation of osteoblast-like cells attached to the surface of the material with scanning electron microscopy and immunofluorescence of cytoskeletal actin as well as their osteogenic development, the ability to mineralize, and their vitality. Following the in-vitro tests a small animal (rat) and big animal (sheep) model were accomplished by inserting a cylindrical titanium implant into a drill hole defect in the femoral condyle. After 7, 14, and 30 days (rat) and 6 months (sheep) the condyles were studied regarding histological and histomorphometrical characteristics. Uncoated and coated material showed a good biocompatibility both in cell culture and animal models. While the defect area in the rat is well consolidated after 30 days, the sheep show only little bone inside the implant after 6 months, possibly due to stress shielding. None of the executed methods indicated a statistically significant difference between coated and uncoated material.

An introduction to bone tissue engineering.

Bone tissue has the capability to regenerate itself; however, defects of a critical size prevent the bone from regenerating and require additional support. To aid regeneration, bone scaffolds created out of autologous or allograft bone can be used, yet these produce problems such as fast degradation rates, reduced bioactivity, donor site morbidity or the risk of pathogen transmission. The development of bone tissue engineering has been used to create functional alternatives to regenerate bone. This can be achieved by producing bone tissue scaffolds that induce osteoconduction and integration, provide mechanical stability, and either integrate into the bone structure or degrade and are excreted by the body. A range of different biomaterials have been used to this end, each with their own advantages and disadvantages. This review will introduce the requirements of bone tissue engineering, beginning with the regeneration process of bone before exploring the requirements of bone tissue scaffolds. Aspects covered include the manufacturing process as well as the different materials used and the incorporation of bioactive molecules, growth factors and cells.

Anterior intermeniscal ligament: frequency in MRI studies and spatial relationship to the entry point for intramedullary tibial nailing related to the risk of iatrogenic violation.

BACKGROUND: Anterior knee pain is the most common complication after intramedullary tibial nailing. Often, the cause is multifactorial and individually different. Violation of the anterior intermeniscal ligament (AIL) during intramedullary tibial nailing might be a possible origin of postsurgical anterior knee pain. Both the importance and function of the AIL remain somewhat ambivalent, and even the figures quoted in the literature for its existence in the population vary drastically. Our aim was to verify the estimated frequency of the AIL in the literature by retrospectively analysing the data of MRI studies conducted at our hospital. In addition, we attempted to assess the potential risk of AIL violation during intramedullary tibial nailing, based on the spatial arrangement. METHODS: Two independent examiners analysed the images generated in 351 MRI studies conducted at our hospital between June 2013 and May 2014. All cases who did not reveal any previous knee-joint injury or osteoarthritis of the knee were allocated to group I. All other cases were included in group II. To estimate the potential risk of AIL injury during the nailing procedure, the distance between the AIL and the theoretical entry point for intramedullary nailing was measured. RESULTS: We identified the AIL on the images of nearly all patients (96.5%) in group I. In group II, the presence of the AIL was confirmed in only 51.4% of cases (p < 0.001). The average distance between the AIL and theoretical entry point for intramedullary tibial nailing was 10.1 mm (range 3.48-18.88 mm). CONCLUSIONS: Because we were able to confirm the presence of the AIL in nearly all patients without a history of knee joint injuries or osteoarthrosis, we presume that the AIL may play a role in knee joint function. Violation of the AIL during intramedullary nailing appears likely due to the close position of the AIL in relation to the entry point for the inserted nail. As a result and due to its rich sensory innervation, a connection between AIL violation during tibial nailing and postoperative onset of anterior knee pain seems likely. To eliminate one risk factor of anterior knee pain development and in view of the unresolved issues of AIL function, violation of the ligament during any operative procedure should be avoided.

Effects of testosterone and 17ß-estradiol on osteogenic and adipogenic differentiation capacity of human bone-derived mesenchymal stromal cells of postmenopausal women.

Progressive bone loss is a predominant symptom of aging and osteoporosis. Therefore, the effects of sex steroids (i.e. testosterone and 17ß-estradiol) on the differentiation capacity of human bone-derived mesenchymal stromal cells (hMSCs), as progenitors of osteoblasts and adipocytes, are of particular interest. The objectives of the present study were, thus, to elucidate whether bone-derived hMSCs of postmenopausal women produce aromatase (CYP19A1) and, whether they modulate their differentiation behaviour in response to testosterone and 17ß-estradiol (E2), in relation to their steroid receptor expression. Supplementation of testosterone resulted in a considerable formation of E2 under osteogenic and adipogenic culture conditions, whereas E2 synthesis remained minimal in the cells cultured in basal medium. Concomitant with high aromatase expression and 17ß-estradiol formation of the cells cultured in osteogenic medium supplemented with testosterone, a distinct promotion of late-stage osteogenesis was found, as shown by significant matrix mineralization and a notable increase in osteogenic markers. These effects were abrogated by the aromatase inhibitor anastrozole. Under adipogenic conditions, testosterone reduced the occurrence of lipid droplets and led to a decrease in PPARγ and AR expression, independent of anastrozole. Regardless of the culture conditions, ERα was detectable whilst ERß was not. In conclusion, aromatase activity is limited to differentiated hMSCs and the resulting 17ß-estradiol enhances late osteogenic differentiation stages via ERα. Adipogenic differentiation, on the other hand, is reduced by both sex steroids: testosterone via AR and 17ß-estradiol.

Comparison of Material-mediated Bone Regeneration Capacities of Sintered and Non-sintered Xenogeneic Bone Substitutes via 2D and 3D Data.

BACKGROUND/AIM: The aim of this study was the development of a new osteoconductivity index to determine the bone healing capacities of bone substitute materials (BSM) on the basis of 3D microcomputed tomographic (µ-CT) data. MATERIALS AND METHODS: Sinus biopsies were used for the comparative analysis of the integration behavior of two xenogeneic BSM (cerabone® and Bio-Oss®). 3D µ-CT and data sets from histomorphometrical measurements based on 2D histological slices were used to measure the bone-material-contact and the tissue distribution within the biopsies. The tissue reactions to both BSM were microscopically analyzed. RESULTS: The 3D and 2D results of the osteoconductivity measurements showed comparable material-bone contacts for both BSM, but the 2D data were significantly lower. The same results were found when tissue distribution was measured in both groups. The histopathological analysis showed comparative tissue reactions in both BSM. CONCLUSION: Osteoconductivity index is a reliable measurement parameter for determining the healing capacities of BSM. The observed differences between both measurement methods could be assigned to the resolution capacity of µ-CT data that did not allow for a precise interface distinction between both BSM and bone tissue. Histomorphometrical data based on histological slides still allow for a more exact evaluation.

Safety assessment of microsilver-loaded poly(methyl methacrylate) (PMMA) cement spacers in patients with prosthetic hip infections: Results of a prospective cohort study.

OBJECTIVES: Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. METHODS: A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3. RESULTS: In total, 11 of the 12 patients completed the study. No argyria or considerable differences in laboratory parameters were detected. Silver blood concentrations were below or around the detection limit of 1 ppb in ten of the 11 patients. A maximum of 5.6 ppb at 48 hours after implantation of the silver spacer, which is below the recommended maximum level of 10 ppb, was found in one patient. No silver was detected in the urine. Drainage fluids showed concentrations between 16.1 ppb and 23.3 ppb at 12 hours after implantation of the silver spacers, and between 16.8 ppb to 25.1 ppb at 48 hours after implantation. Pathohistological assessment of the periprosthetic membrane did not reveal any differences between the two groups. CONCLUSION: Microsilver-loaded gentamicin-PMMA spacers showed good biocompatibility and the broad antimicrobial activity warrants further clinical research to assess its effectivity in reducing infection rates in prosthetic joint infection.Cite this article: V. Alt, M. Rupp, K. Lemberger, T. Bechert, T. Konradt, P. Steinrücke, R. Schnettler, S. Söder, R. Ascherl. Safety assessment of microsilver-loaded poly(methyl methacrylate) (PMMA) cement spacers in patients with prosthetic hip infections: Results of a prospective cohort study. Bone Joint Res 2019;8:387-396. DOI: 10.1302/2046-3758.88.BJR-2018-0270.R1.

The Addition of High Doses of Hyaluronic Acid to a Biphasic Bone Substitute Decreases the Proinflammatory Tissue Response.

Biphasic bone substitutes (BBS) are currently well-established biomaterials. Through their constant development, even natural components like hyaluronic acid (HY) have been added to improve both their handling and also their regenerative properties. However, little knowledge exists regarding the consequences of the addition of HY to their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted, aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY), combined with a BBS, on in vitro biocompatibility and in vivo tissue reaction. Established in vitro procedures, using L929 cells, were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo part of the study, calvarial defects were created in 20 Wistar rats and subsequently filled with BBS, and BBS combined with two different HMWHY amounts, i.e., BBS + HY(L) and BBS + HY(H). As controls, empty defects were used. Established histological, immunohistochemical, and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damage to the L929 cells and can be considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of pro-inflammatory macrophages (* p < 0.05), comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to BBS, while improving the material handling properties.

Improved In Vitro Test Procedure for Full Assessment of the Cytocompatibility of Degradable Magnesium Based on ISO 10993-5/-12.

Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nevertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continuous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristics were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and osteogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations.

Additive Manufacturing for Guided Bone Regeneration: A Perspective for Alveolar Ridge Augmentation.

Three-dimensional (3D) printing has become an important tool in the field of tissue engineering and its further development will lead to completely new clinical possibilities. The ability to create tissue scaffolds with controllable characteristics, such as internal architecture, porosity, and interconnectivity make it highly desirable in comparison to conventional techniques, which lack a defined structure and repeatability between scaffolds. Furthermore, 3D printing allows for the production of scaffolds with patient-specific dimensions using computer-aided design. The availability of commercially available 3D printed permanent implants is on the rise; however, there are yet to be any commercially available biodegradable/bioresorbable devices. This review will compare the main 3D printing techniques of: stereolithography; selective laser sintering; powder bed inkjet printing and extrusion printing; for the fabrication of biodegradable/bioresorbable bone tissue scaffolds; and, discuss their potential for dental applications, specifically augmentation of the alveolar ridge.

Importance of Mechanoreceptors and Other Neural Structures Within the Anterior Intermeniscal Ligament in the Etiology of Anterior Knee Pain After Tibial Nailing.

BACKGROUND: Anterior knee pain is the most common complication after intramedullary tibial nailing. The cause is often multifactorial and varies among individuals. Violation of the anterior intermeniscal ligament (AIL) during intramedullary tibial nailing might be a possible source of postsurgical anterior knee pain. Although there is a certain ambiguity regarding the importance and function of the AIL, neural structures in the AIL tissue might play a significant role with respect to functional purposes and pain perception. METHODS: We subjected 6 AIL specimens to histologic examination to identify the neural structures that are a mandatory requirement as a source of anterior knee pain. Specifically, we performed three-dimensional immunohistochemical investigation of subtyping, orientation, and detailed characterization of neural structures within the AIL tissue. RESULTS: Histologic and three-dimensional immunohistochemical examinations confirmed the presence of neural structures in all 6 AIL specimens. We identified myelinated and unmyelinated nerve fibers, as well as all types of mechanoreceptors. CONCLUSIONS: Free nerve endings are a mandatory requirement for pain perception as a result of AIL violation during tibial nailing. Our verification of all different types of mechanoreceptors in the AIL tissue makes a role of the ligament in knee joint function and proprioception highly probable. Further investigations are necessary to clarify possible correlations between neural supply and function of the AIL. Violation of the ligament during operative procedures should be avoided, although the significance of the AIL is still debated.

In Vivo Analysis of the Biocompatibility and Macrophage Response of a Non-Resorbable PTFE Membrane for Guided Bone Regeneration.

The use of non-resorbable polytetrafluoroethylene (PTFE) membranes is indicated for the treatment of large, non-self-containing bone defects, or multi-walled defects in the case of vertical augmentations. However, less is known about the molecular basis of the foreign body response to PTFE membranes. In the present study, the inflammatory tissue responses to a novel high-density PTFE (dPTFE) barrier membrane have preclinically been evaluated using the subcutaneous implantation model in BALB/c mice by means of histopathological and histomorphometrical analysis methods and immunohistochemical detection of M1- and M2-macrophages. A collagen membrane was used as the control material. The results of the present study demonstrate that the tissue response to the dPTFE membrane involves inflammatory macrophages, but comparable cell numbers were also detected in the implant beds of the control collagen membrane, which is known to be biocompatible. Although these data indicate that the analyzed dPTFE membrane is not fully bioinert, but its biocompatibility is comparable to collagen-based membranes. Based on its optimal biocompatibility, the novel dPTFE barrier membrane may optimally support bone healing within the context of guided bone regeneration (GBR).

Vertical bone augmentation in a single-tooth gap with an allogenic bone ring: Clinical considerations.

OBJECTIVE: The main objective of this case report is to introduce a one-stage bone block augmentation with a cylindrical freeze-dried bone allograft (FDBA) and simultaneous implantation for the reconstruction of a single-tooth bone defect. CLINICAL CONSIDERATIONS: The report describes this method on the basis of radiographical and clinical images derived from a single patient. CONCLUSIONS: The report demonstrates the time-saving and successful application of this treatment concept, which has the potential to increase patient satisfaction and comfort. CLINICAL SIGNIFICANCE: The application of the presented technique enabled a prosthetic rehabilitation of the extracted tooth about 3 months earlier as compared to the conventional procedure, while demonstrating no compromises regarding clinical outcome, functionality and esthetics.