0000000000498134

AUTHOR

Robert Sader

Injectable Bone Substitute Based on β-TCP Combined With a Hyaluronan-Containing Hydrogel Contributes to Regeneration of a Critical Bone Size Defect Towards Restitutio ad Integrum.

In the present in vivo study, the regenerative potential of a new injectable bone substitute (IBS) composed of beta-tricalcium phosphate (β-TCP) and hyaluronan was tested in a rabbit distal femoral condyle model. To achieve this, 2 defects of 6 mm in diameter and 10 mm in length were drilled into each femur condyle in a total of 12 animals. For each animal, 1 hole was filled with the substitute material, and the other was left empty to serve as the control. After 1, 3, and 6 months, the regenerative process was analyzed by radiography as well as by histological and histomorphometrical analysis. The results revealed that bone tissue formation took place through osteoconductive processes over…

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High-Temperature Sintering of Xenogeneic Bone Substitutes Leads to Increased Multinucleated Giant Cell Formation: In Vivo and Preliminary Clinical Results.

The present preclinical and clinical study assessed the inflammatory response to a high-temperature–treated xenogeneic material (Bego-Oss) and the effects of this material on the occurrence of multinucleated giant cells, implantation bed vascularization, and regenerative potential. After evaluation of the material characteristics via scanning electron microscopy, subcutaneous implantation in CD-1 mice was used to assess the inflammatory response to the material for up to 60 days. The clinical aspects of this study involved the use of human bone specimens 6 months after sinus augmentation. Established histologic and histomorphometric analysis methods were applied. After implantation, the mat…

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The chemical composition of synthetic bone substitutes influences tissue reactions in vivo : histological and histomorphometrical analysis of the cellular inflammatory response to hydroxyapatite, beta-tricalcium phosphate and biphasic calcium phosphate ceramics

Bone substitute material properties such as granule size, macroporosity, microporosity and shape have been shown to influence the cellular inflammatory response to a bone substitute material. Keeping these parameters constant, the present study analyzed the in vivo tissue reaction to three bone substitute materials (granules) with different chemical compositions (hydroxyapatite (HA), beta-tricalcium phosphate (TCP) and a mixture of both with a HA/TCP ratio of 60/40 wt%). Using a subcutaneous implantation model in Wistar rats for up to 30 days, tissue reactions, including the induction of multinucleated giant cells and the extent of implantation bed vascularization, were assessed using histo…

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Scaffold vascularization in vivo driven by primary human osteoblasts in concert with host inflammatory cells.

Successful cell-based tissue engineering requires a rapid and thorough vascularization in order to ensure long-term implant survival and tissue integration. The vascularization of a scaffold is a complex process, and is modulated by the presence of transplanted cells, exogenous and endogenous signaling proteins, and the host tissue reaction, among other influencing factors. This paper presents evidence for the significance of pre-seeded osteoblasts for the in vivo vascularization of a biodegradable scaffold. Human osteoblasts, cultured on silk fibroin micronets in vitro, migrated throughout the interconnected pores of the scaffold and produced extensive bone matrix. When these constructs we…

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Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic.

This study evaluates a new collagen matrix that is designed with a bilayered structure in order to promote guided tissue regeneration and integration within the host tissue. This material induced a mild tissue reaction when assessed in a murine model and was well integrated within the host tissue, persisting in the implantation bed throughout the in vivo study. A more porous layer was rapidly infiltrated by host mesenchymal cells, while a layer designed to be a barrier allowed cell attachment and host tissue integration, but at the same time remained impermeable to invading cells for the first 30 days of the study. The tissue reaction was favorable, and unlike a typical foreign body respons…

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Influence of E-smoking liquids on human periodontal ligament fibroblasts.

Introduction: Over the last years, electronic cigarettes (ECs) have become more popular, particularly in individuals who want to give up smoking tobacco. The aim of the present study was to assess the influence of the different e-smoking liquids on the viability and proliferation of human periodontal ligament fibroblasts. Method and materials: For this study six test solutions with components from ECs were selected: lime-, hazelnut- and menthol-flavored liquids, nicotine, propylene glycol, and PBS as control group. The fibroblasts were incubated up to 96 h with the different liquids, and cell viability was measured by using the PrestoBlue® reagent, the ATP detection and the migration assay.…

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Heterogeneity of biomaterial-induced multinucleated giant cells: Possible importance for the regeneration process?

Biomaterial-associated multinucleated giant cells (BMGCs) have been found within the implantation beds of many different biomaterials. However, their exact differentiation and their involvement in the inflammatory and healing events of the foreign body response still remain mostly unclear. Silk fibroin (SF) scaffolds, which induces a tissue reaction involving both macrophages and BMGCs, was implanted in the subcutaneous connective tissue of four CD-1 mice for 15 days using an established subcutaneous implantation model. Analysis of macrophage polarization and BMGCs was performed by immunohistochemcial detection of pro- (cyclooxygenase-2 (COX-2), C-C chemokine receptor type 7 (CCR7), nuclear…

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Nanocrystalline Hydroxyapatite Bone Substitute Leads to Sufficient Bone Tissue Formation Already after 3 Months: Histological and Histomorphometrical Analysis 3 and 6 Months following Human Sinus Cavity Augmentation

Purpose: In this study the de novo bone formation capacity of a nanocrystalline hydroxyapatite bone substitute was assessed 3 and 6 months after its insertion into the human sinus cavity. Materials and Methods: Sinus cavity augmentation was performed in a total of 14 patients (n = 7 implantation after 3 months; n = 7 implantation after 6 months) with severely atrophic maxillary bone. The specimens obtained after 3 and 6 months were analyzed histologically and histomorphometrically with special focus on bone metabolism within the residual bone and the augmented region. Results: This study revealed that bone tissue formation started from the bone-biomaterial-interface and was directed into th…

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Multinucleated giant cells in the implant bed of bone substitutes are foreign body giant cells-New insights into the material-mediated healing process

In addition to macrophages, multinucleated giant cells (MNGCs) are involved in the tissue reaction to a variety of biomaterials. Especially in the case of bone substitute materials it has been assumed that the MNGCs are osteoclasts, based on the chemical and physical similarity of many materials to the calcified matrix and the bony environment in which they are used. However, many studies indicate that these cells belong to the cell line of the foreign body giant cells (FBGCs), which are of "inflammatory origin", although they have been shown to possess both a pro- and also anti-inflammatory phenotype. Moreover, no information is available about their role in the tissue reaction to bone sub…

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TRAP-Positive Multinucleated Giant Cells Are Foreign Body Giant Cells Rather Than Osteoclasts: Results From a Split-Mouth Study in Humans

This study compared the material-specific tissue response to the synthetic, hydroxyapatite-based bone substitute material NanoBone (NB) with that of the xenogeneic, bovine-based bone substitute material Bio-Oss (BO). The sinus cavities of 14 human patients were augmented with NB and BO in a split-mouth design. Six months after augmentation, bone biopsies were extracted for histological and histomorphometric investigation prior to dental implant insertion. The following were evaluated: the cellular inflammatory pattern, the induction of multinucleated giant cells, vascularization, the relative amounts of newly formed bone, connective tissue, and the remaining bone substitute material. NB gra…

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Porcine Dermis-Derived Collagen Membranes Induce Implantation Bed Vascularization Via Multinucleated Giant Cells: A Physiological Reaction?

In this study, the tissue reactions to 2 new porcine dermis-derived collagen membranes of different thickness were analyzed. The thicker material (Mucoderm) contained sporadically preexisting vessel skeletons and fatty islands. The thinner membrane (Collprotect) had a bilayered structure (porous and occlusive side) without any preexisting structures. These materials were implanted subcutaneously in mice to analyze the tissue reactions and potential transmembranous vascularization. Histological and histomorphometrical methodologies were performed at 4 time points (3, 10, 15, and 30 days). Both materials permitted stepwise connective tissue ingrowth into their central regions. In the Mucoderm…

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Non-cross-linked collagen type I/III materials enhance cell proliferation: in vitro and in vivo evidence

Objective: To analyze Mucograft®(MG), a recently introduced collagen matrix, in vitro and in vivo, and compare it with BioGide®(BG), a well-established collagen membrane, as control. Material and Methods: A detailed analysis of the materials surface and ultra-structure was performed. Cellular growth patterns and proliferation rates of human fibroblasts on MG and BG were analyzed in vitro. In addition, the early tissue reaction of CD-1 mouse to these materials was analyzed by means of histological and histomorphometrical analysis. Results: MG showed a three-fold higher thickness both in dry and wet conditions, when compared to BG. The spongy surface of BG significantly differed from that of …

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Self-drilling and self-tapping miniscrews for osteosynthesis fixture after LeFort I osteotomy: An ex vivo trial for primary stability and a randomized clinical study.

Abstract Background Self-drilling osteosynthesis screws (SDS) have a potential higher primary stability together with clinical advantages such as less time effort compared to self-tapping screws (STS). The aims of the study were to compare the primary stability of SDS and STS ex vivo and to analyze of the time-saving effect in vivo . Materials and methods Ex vivo , both screws were placed in porcine bone. Torque was measured for insertion and removal. Four specimens were kept in bone for histologic bone-to-implant-contact examination. In vivo , 49 patients who received orthognathic surgery in the maxilla were included in 2 centers. In a split-mouth design, the time for osteosynthesis fixati…

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Bovine pericardium based non-cross linked collagen matrix for successful root coverage, a clinical study in human

Abstract Introduction The aim of this study was to clinically assess the capacity of a novel bovine pericardium based, non-cross linked collagen matrix in root coverage. Methods 62 gingival recessions of Miller class I or II were treated. The matrix was adapted underneath a coronal repositioned split thickness flap. Clinical values were assessed at baseline and after six months. Results The mean recession in each patient was 2.2 mm at baseline. 6 Months after surgery 86.7% of the exposed root surfaces were covered. On average 0,3 mm of recession remained. The clinical attachment level changed from 3.5 ± 1.3 mm to 1,8 ( ± 0,7) mm during the observational time period. No statistically signifi…

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PTCH-1 and MDM2 expression in ameloblastoma from a West African sub-population: implication for chemotherapeutics

INTRODUCTION: ameloblastoma is a slow growing, painless odontogenic swelling which can attain sizes that result in severe deformities of the craniofacial complex. It is the most commonly encountered odontogenic tumor in Nigeria. Surgical intervention is currently the method of treatment; however identification of altered molecular pathways may inform chemotherapeutic potential. The Protein Patched homolog 1 (PTCH-1) is overexpressed in ameloblastoma. Also, mutation in the MDM2 gene can reduce the tumor suppressor function of p53 and promote ameloblastoma growth. No study however has characterized the molecular profile of African cases of ameloblastoma with a view to developing chemotherapeu…

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Porcine Dermis and Pericardium-Based, Non–Cross-Linked Materials Induce Multinucleated Giant Cells After Their In Vivo Implantation: A Physiological Reaction?

The present study analyzed the tissue reaction to 2 novel porcine-derived collagen materials: pericardium versus dermis. By means of the subcutaneous implantation model in mice, the tissue reactions were investigated at 5 time points: 3, 10, 15, 30, and 60 days after implantation. Histologic, histochemical, immunhistologic, and histomorphometric analysis methodologies were applied. The dermis-derived material underwent an early degradation while inducing mononuclear cells together with some multinucleated giant cells and mild vascularization. The pericardium-derived membrane induced 2 different cellular tissue reactions. The compact surface induced mononuclear cells and multinucleated giant…

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Treatment of malar and midfacial fractures with osteoconductive forged unsintered hydroxyapatite and poly-L-lactide composite internal fixation devices.

Purpose To evaluate the internal fixation of malar and midfacial fractures, long-term results, and biocompatibility of osteoconductive internal fixation devices composed of a forged composite of unsintered hydroxyapatite and poly-L-lactide (F-u-HA/PLLA). Materials and Methods From January 2006 to June 2010, 29 patients (24 males and 5 females; age 33 ± 15 years) were included in the present prospective study. The fracture type was malar in 24 patients, midfacial in 5, isolated orbital floor blowout in 2, and frontal sinus, cranial base in 2 patients. The fractures were fixed with internal fixation devices; these were plates and screws composed of F-u-HA/PLLA. The 24 patients with malar frac…

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Nanocrystalline Hydroxyapatite-Based Material Already Contributes to Implant Stability After 3 Months: A Clinical and Radiologic 3-Year Follow-up Investigation

The present study reports on a 3-year clinical and radiologic follow-up investigation of dental implants placed 3 and 6 months after sinus augmentation in 14 patients. Augmentation was performed with a synthetic bone substitute material composed of nanocrystalline hydroxyapatite. The aim of the study was to determine how the integration period of the bone substitute material, that is, 3 months or 6 months, influences implant integration within the patient's upper jaw. Therefore, the following clinical and radiologic parameters were investigated: implant being in situ; Periotest value; and presence of peri-implant osteolysis, bleeding on probing, plaque, and soft tissue recession around the …

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Influence of β-tricalcium phosphate granule size and morphology on tissue reaction in vivo.

In this study the tissue reaction to five different β-tricalcium phosphate (β-TCP)-based bone substitute materials differing only in size, shape and porosity was analyzed over 60 days, at 3, 10, 15, 30 and 60 days after implantation. Using the subcutaneous implantation model in Wistar rats both the inflammatory response within the implantation bed and the resulting vascularization of the biomaterials were qualitatively and quantitatively assessed by means of standard and special histological staining methods. The data from this study showed that all investigated β-TCP bone substitutes induced the formation of multinucleated giant cells. Changes in size, shape and porosity influenced the int…

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Addition of blood to a phycogenic bone substitute leads to increased in vivo vascularization

The present study aimed to analyze the effects of the addition of blood to the phycogenic bone substitute Algipore(®) on the severity of in vivo tissue reaction. Initially, Fourier-transform infrared spectroscopy (FTIR) of the bone substitute was conducted to analyze its chemical composition. The subcutaneous implantation model in Balb/c mice was then applied for up to 30 d to analyze the tissue reactions on the basis of specialized histochemical, immunohistochemical, and histomorphometrical methods. The data of the FTIR analysis showed that the phycogenic bone substitute material is mainly composed of hydroxyapatite with some carbonate content. The in vivo analyses revealed that the additi…

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Foreign Body Giant Cell–Related Encapsulation of a Synthetic Material Three Years After Augmentation

Bone substitute materials of different origin and chemical compositions are frequently used in augmentation procedures to enlarge the local bone amount. However, relatively little data exist on the long-term tissue reactions. The presented case reports for the first time histological and histomorphometrical analyses of a nanocrystaline hydroxyapatite–based bone substitute material implanted in the human sinus cavity after an integration period of 3 years. The extracted biopsy was analyzed histologically and histomorphometrically with focus on the tissue reactions, vascularization, new bone formation, and the induction of a foreign body reaction. A comparably high rate of connective tissue (…

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Advanced Platelet-Rich Fibrin: A New Concept for Cell-Based Tissue Engineering by Means of Inflammatory Cells

Choukroun's platelet-rich fibrin (PRF) is obtained from blood without adding anticoagulants. In this study, protocols for standard platelet-rich fibrin (S-PRF) (2700 rpm, 12 minutes) and advanced platelet-rich fibrin (A-PRF) (1500 rpm, 14 minutes) were compared to establish by histological cell detection and histomorphometrical measurement of cell distribution the effects of the centrifugal force (speed and time) on the distribution of cells relevant for wound healing and tissue regeneration. Immunohistochemistry for monocytes, T and B -lymphocytes, neutrophilic granulocytes, CD34-positive stem cells, and platelets was performed on clots produced from four different human donors. Platelets …

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