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Mesh implants as standard treatment for tissue defects can be adapted to patient’s needs by specific bioactive coatings. The biophysical interaction with the surrounding tissue must be understood to describe the influence of coatings qualitatively and quantitatively. This study investigates the use of meshes to repair diaphragmatic defects. The physical stress in this tissue is high in comparison to other applications. Therefore, knowledge gained from this experimental model can be applied to other locations. Meshes were implanted on surgically created diaphragmatic defects in growing rabbits. A standardized load model was used to investigate 33 rabbits. The commercial products Ultrapro®, Surgisis®, and Proceed ® were implanted. The adhesive properties of the meshes as well as the defect size were determined macroscopically at explantation after 4 months. Sections of the explanted meshes and diaphragms were examined histologically and immunohistochemically. The median defect size for all mesh groups decreased from the initial size of 10 mm down to 4.5 mm at explantation. No statistically significant differences were seen between the three mesh groups. Surgisis ® was found to be completely disintegrated after 4 months. Ultrapro ® and Proceed® showed no macroscopic differences compared to their original appearance. Both sealed the original diaphragmatic defect as tightly as at time of implantation. Histological and immunohistochemical analyses showed significant differences between the three mesh groups. Proceed ® caused stronger inflammatory reaction in the surrounding tissue and inferior connective tissue formation. Regarding the composition of the newly generated tissue within the defect area, Ultrapro® and Surgisis® were found superior. This can sufficiently be explained by the different gradient of inflammatory reaction in the surrounding tissue. Because Surgisis® offers no sufficiently lasting support for the diaphragmatic defect, our future main focus for mesh modification is laid on Ultrapro®. [ABSTRACT FROM AUTHOR]

Abstract: The porous TiO2/glass composite Ecopore has potential applications in hard tissue replacement. We describe the modification of Ecopore with the growth factor bone morphogenetic protein-2 (BMP-2) to add osteoinductive properties. Ecopore covalently coated with BMP-2 caused a weak induction of alkaline phosphatase in murine embryonal fibroblasts. In a rabbit bone defect model, BMP-2-coated Ecopore had moderately higher bone apposition rates and ingrown bone quantities at 6 weeks after implantation. To overcome loss of function due to chemical surface coupling, we filled the pore system of Ecopore with heparinized collagen sponge and loaded this secondary matrix with BMP-2. Heparinization of collagen filling increased the BMP-2 loading capacity of the matrix approximately 1.28-fold. Within 96h, 17.0±0.1 and 10.1±0.2% of the used BMP-2 was released from non-modified and heparinized Ecopore/collagen, respectively, indicating that the heparin modification retarded BMP-2 release. Revealed by energy-dispersive X-ray spectroscopy analysis of implant cross-sectional areas, BMP-2-loaded Ecopore/collagen had significantly higher bony ingrowth quantities in rabbits, with the heparinized modification yielding the highest value (16.09±3.51%, p <0.005) compared with the non-heparinized matrix (10.72±4.07%, p <0.05) and the BMP-2-free controls (5.60±1.47%). This suggested a beneficial effect of the biomimetic modification of Ecopore with heparinized collagen for bone healing and integration. [Copyright &y& Elsevier]

Introduction: Even following the introduction of the "third generation" cementing technique, an improvement of the fixation of the acetabular component similar to that of the femoral has not been shown in clinical studies. The goal of the present study was to achieve a better stability with the use of an amphiphilic bonder while preserving the mechanically important subchondral sclerosis. Materials and Methods: In a total of 20 sheep, a cemented total hip replacement was implanted. In the treatment group (n = 10), the implantation was carried out following surface conditioning of the acetabular bed with an amphiphilic bonder. All the sheep were followed for 9 months. To assess the biocompatibility, the osseous ingrowth at the cement-bone interface was depicted with the help of an in vivo fluorescent marking of the osteoblasts. Additionally, conventional radiographs were obtained over the course of treatment. Finally, the ovine pelvic regions were split following a standardized technique allowing for histological evaluation of the cement-bone interfaces. Results: The acetabular components of the treatment group revealed a stable cement-bone compound. In the control group, the implants were easily dislodged from their beds. This finding was consistent with the radiological and histological results, which had revealed increased, progressive lytic radiolucent lines and the interposition of fibrous tissue at the cement-bone interface in the control group compared to the treatment group. The bonder was biocompatible. Conclusion: Following the application of the bonder, the cemented acetabular components revealed an improved stability without signs of inflammation or neoplasia in a viable acetabular osseous bed. With the help of this technique, the in vivo longevities of cemented acetabular components can be increased in the clinical setting without sacrificing the biomechanical relevant subchondral sclerosis. [ABSTRACT FROM AUTHOR]

Abstract The aim of the present study was to analyze the osteogenic potential of a biphasic calcium composite material (BCC) with a negative surface charge for maxillary sinus floor augmentation. In a 61 year old patient, the BCC material was used in a bilateral sinus floor augmentation procedure. Six months postoperative, a bone sample was taken from the augmented regions before two titanium implants were inserted at each side. We analyzed bone neoformation by histology, bone density by computed tomography, and measured the activity of voltage-activated calcium currents of osteoblasts and surface charge effects. Control orthopantomograms were carried out five months after implant insertion. The BCC was biocompatible and replaced by new mineralized bone after being resorbed completely. The material demonstrated a negative surface charge (negative Zeta potential) which was found to be favorable for bone regeneration and osseointegration of dental implants.

Objectives: The aim of this study was to evaluate whether thermal implant removal of osseointegrated implants is possible using a diode laser with an specific temperature-time interval., Materials and Methods: First, tooth extraction of the first three premolars was performed in the maxilla and mandible on both sides of 10 pig. After 3 months, implants were inserted into the upper and lower jaws of 10 pigs. After 3 more months, osseointegrated implants were heated with a laser device to a temperature of 50 °C for 1 min. After 14 days, the implant stability quotient (ISQ), torque-out values, and bone-to-implant contact (BIC) ratio were assessed using resonance frequency analysis., Results: ISQ values showed no significant differences within each group or between the control and test groups. Furthermore, torque-out and BIC value measurements presented no significant differences between the groups., Conclusions: At 50°C, changes in the BIC values were noticeably smaller; however, these differences were not significant. Future studies should evaluate the same procedures at either a higher temperature or longer intervals., Clinical Relevance: With only 50 °C for 1 min, a dental implant will not de-integrate predictably., (© 2024. The Author(s).)

Background: The purpose of this study was to evaluate the osseointegration of zirconia and titanium implants in the rat maxilla in specimens under systemic antiresorptive therapy., Materials and Methods: After 4 weeks of systematic medication administration (either zoledronic acid or alendronic acid), 54 rats received one zirconia and one titanium implants that were immediately inserted in the rat maxilla after tooth extraction. Twelve weeks after implant placement, histopathological samples were evaluated for implant osteointegration parameters., Results: The bone-implant-contact (BIC) ratio revealed no significant inter-group or inter-material differences. The distance between the implant shoulder to the bone level was significantly greater around the titanium implants of the zoledronic acid group compared to the zirconia implants of the control group (p = 0.0005). On average, signs of new bone formation could be detected in all groups, although often without statistical differences. Signs of bone necrosis were only detected around the zirconia implants of the control group (p < 0.05)., Conclusions: At the 3-month follow-up, no implant material was demonstrably better than the others in terms of osseointegration metrics under systemic antiresorptive therapy. Further studies are necessary to determine whether there are differences in the osseointegration behavior of the different materials., (© 2023. The Author(s).)

The purpose of this rat study was to explore the feasibility of in vivo temperature thresholds affecting bone contact at the implant surface. Based on these data, thermal necrosis should be used for implant removal in the subsequent in vivo study. Rat tibiae of 48 animals at one site were randomly treated with heat or cold before implant insertion. Temperatures of 4 °C, 3 °C, 2 °C, 48 °C, 49 °C and 50 °C for a tempering time of 1 min were evaluated. Numerical simulations of the heat source-implant-bone system were carried out. Effects were assessed by histomorphometrical measurements. The results showed that the selected method of direct tempering using a tempering pin was suitable for maintaining a uniform layer around the pin. Starting at warm temperatures of 48 °C and rising to 50 °C, the BIC ratio revealed declining values and a significant difference was observed when comparing 50 °C to the control group (p = 0.03). However, there were no significant variations within the cold temperatures. This study pinpointed temperature discovered that could lead to the thermo-explantation and so that the number of samples used in future studies on temperature-induced bone necrosis can be reduced to a minimum. Significant BIC value reduction was seen at a temperature of 50 °C for 1 min., (© 2022. The Author(s).)

Background: The evaluation of bone remodelling and dental root resorption can be performed by histological techniques or micro-computed tomography (micro-CT). The present study aimed to evaluate the relationship between these two procedures in the context of cleft repair in a rat model., Methods: The reconstructed maxillae and the orthodontically-moved first molar of 12 rats were analysed for correlations between the histological and radiological findings retrospectively. The alveolar cleft repairs were performed using bone autografts or (human) xenografts. Four weeks after the operation, the intervention of the first molar protraction was initiated and lasted for eight weeks. The newly formed bone and the root resorption lacunae were determined via histology. In the micro-CT analysis, the average change of bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness and trabecular separation of the jaw, as well as the volume of the root resorptions were determined. The Pearson correlation coefficient was applied to study the associations between groups., Results: Positive correlations were found only between the newly formed bone (histology) and BMD changes (micro-CT) in the autograft group (r = 0.812, 95% CI: 0.001 to 0.979, p = 0.05). The relationship of newly formed bone and BV/TV was similar but not statistically significant (r = 0.691, 95% CI: -0.274 to 0.963, p = 0.013). Regarding root resorption, no significant correlations were found., Conclusions: Due to the lack of correlation between histological and radiological findings of bone remodelling and the development of root resorptions, both methods should be combined in this cleft model in rats for a comprehensive analysis., (© 2022. The Author(s).)

Objective: The aim of the present study was to investigate the influence of three grafting materials for cleft repair on orthodontic tooth movement in rats., Materials and Methods: Artificial alveolar clefts were created in 21 Wistar rats and were repaired 4 weeks later using autografts, human xenografts and synthetic bone substitute (beta-tricalcium phosphate/hydroxyapatite [β-TCP/HA]). A further 4 weeks later, the first molar was moved into the reconstructed maxilla. Microfocus computed tomography (μCT) was performed six times (T0-T5) to assess the tooth movement and root resorption. After 8 weeks, the affected reconstructed jaw was resected for histopathological investigation., Results: Total distances reached ranged from 0.82 ± 0.72 mm (β-TCP/HA) to 0.67 ± 0.27 mm (autograft). The resorption was particularly determined at the mesiobuccal root. Descriptive tooth movement slowed and root resorption increased slightly. However, neither the radiological changes during tooth movement (µCT T1 vs. µCT T5: autograft 1.85 ± 0.39 mm 3 vs. 2.38 ± 0.35 mm 3 , p = 0.30; human xenograft 1.75 ± 0.45 mm 3 vs. 2.17 ± 0.26 mm 3 , p = 0.54; β-TCP/HA: 1.52 ± 0.42 mm 3 vs. 1.88 ± 0.41 mm 3 , p = 0.60) nor the histological differences after tooth movement (human xenograft: 0.078 ± 0.05 mm 2 ; β-TCP/HA: 0.067 ± 0.049 mm 2 ; autograft: 0.048 ± 0.015 mm 2 ) were statistically significant., Conclusion: The autografts, human xenografts or synthetic bone substitute used for cleft repair seem to have a similar effect on the subsequent orthodontic tooth movement and the associated root resorptions., Clinical Relevance: Development of root resorptions seems to have a secondary role in choosing a suitable grafting material for cleft repair., (© 2022. The Author(s).)

Introduction: In free flaps, 5%-10% of complications are related to failure of sutured vascular anastomoses. Adhesive-based microvascular anastomoses are potential alternatives but are associated with failure rates of 70% in research studies. VIVO is a new adhesive with slow biodegradation within 6 months that has shown a 100% patency rate in research studies over 2 h observation time but long-term patency has not been evaluated. The authors hypothesize that VIVO will enable a reliable microvascular procedure comparable to sutured anastomoses over a 28-day period., Materials and Methods: The right common carotid artery of 60 male Sprague Dawley rats, ~450 g, were used for microvascular end-to-end anastomosis. VIVO was applied with reduced sutures with a temporary catheter in one group and in the other with a custom-shaped memory stent. Anastomoses with eight interrupted sutures served as control. All groups were n = 20. Anastomosis time and bleeding were recorded for each procedure. Doppler flowmetry was performed 20 min, 1, 10, and 28 days postoperatively. Postmortem toluidine staining was used for semi-quantitative analysis of stenosis, thrombosis, necrosis, and aneurysm formation by histologic evaluation., Results: No occlusion was detected 20 min and 1 day postoperative, and after 28 days of observation in all anastomoses. The anastomosis time of the VIVO with catheter group was about 32% significantly faster than the VIVO with stent group. In the VIVO group with stent, the bleeding time was ~80% shorter than in the control group with 2.1 ± 0.3 and VIVO with catheter 2.0 ± 0.5 (p ≤ .001 each). Minor and nonsignificant stent-associated thrombus formation and stent-typical intraluminal stenosis were detected exclusively in the VIVO with stent group., Conclusion: Within the limitations of a rat study, the use of VIVO in anastomosis showed promising results. VIVO with catheter was found to be advantageous., (© 2022 The Authors. Microsurgery published by Wiley Periodicals LLC.)

In microsurgical anastomosis, non-synthetic fibrin-based adhesives have predominantly shown superior properties to synthetic cyanoacrylates, but they have hardly any clinical application. This study aims to investigate the local and systemic effects of synthetically produced biodegradable adhesive VIVO when used in microsurgical anastomosis. VIVO is used in two different anastomosis procedures in the common carotid artery in a rat model: VIVO in addition to a temporary catheter (VIVO TC) and VIVO with a custom-shaped memory nitinol stent (VIVO SM). Conventionally sutured anastomoses serve as controls (C). Tissue response is assessed by in vivo fluorescence imaging and histological examination. The systemic effects of biodegradation are measured using hematologic parameters and serum levels of transaminase activity and lactate dehydrogenase. Finally, the degree of local adhesion of the different anastomotic procedures is evaluated. Fluorescence imaging shows reduced inflammatory blood flow in the VIVO TC group. Histological analysis of the anastomosed vessels also reveals significantly more inflammation in C than in the two adhesive groups. The severity of VIVO adhesions proves acceptable, and no histotoxic effects of VIVO are detected. The data demonstrate that the synthetic tissue adhesive VIVO is a reliable and-compared to sutures-tissue-friendly adhesive for microsurgical anastomoses., (© 2022 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

To minimize the postoperative risks posed by grafting autologous transplants for cleft repair, efforts are being made to improve grafting materials for use as potential alternatives. The aim of this study was to compare the bone graft quality of different bone substitutes including the gold standard autografts during the healing processes after cleft repair in the context of orthodontic treatment. In 21 Wistar rats, a complete, continuity-interrupting cleft was created. After 4 weeks, cleft repair was performed using autografts from the hips' ischial tuberosity, human xenografts, or synthetic bone substitutes [beta-tricalcium phosphate (β-TCP)/hydroxyapatite (HA)]. After another 4 weeks, the first molar movement was initiated in the reconstructed jaw for 8 weeks. The bone remodeling was analyzed in vivo using micro-computed tomography (bone mineral density and bone volume fraction) and histology (new bone formation). All the grafting materials were statistically different in bone morphology, which changed during the treatment period. The β-TCP/HA substitute demonstrated less resorption compared to the autologous and xenogeneic/human bone, and the autografts led to a stronger reaction in the surrounding bone. Histologically, the highest level of new bone formation was found in the human xenografts, and the lowest was found in the β-TCP/HA substitute. The differences between the two bone groups and the synthetic materials were statistically significant. Autografts were confirmed to be the gold standard in cleft repair with regard to graft integration. However, parts of the human xenograft seemed comparable to the autografts. Thus, this substitute could perhaps be used as an alternative after additional tissue-engineered modification.

In two proof-of-concept studies, we established and validated the Bacterial Growth Inhibition Screen (BGIS), which explores recombinant protein toxicity in Escherichia coli as a largely overlooked and alternative means for basic characterization of functional eukaryotic protein domains. By applying BGIS, we identified an unrecognized RNA-interacting domain in the DEK oncoprotein (this study) and successfully combined BGIS with random mutagenesis as a screening tool for loss-of-function mutants of the DNA modulating domain of DEK [1]. Collectively, our findings shed new light on the phenomenon of recombinant protein toxicity in E. coli. Given the easy and rapid implementation and wide applicability, BGIS will extend the repertoire of basic methods for the identification, analysis and unbiased manipulation of proteins., (© 2021 Federation of European Biochemical Societies.)

Objectives: The purpose of this pilot porcine cadaver study was to evaluate the feasible temperature thresholds, which affect osteocyte viability and bone matrix in a preclinical setup, assessing the potential of thermal necrosis for implant removal for further in vivo investigations., Materials and Methods: After implant bed preparation in the upper and lower jaw, temperature effects on the bone were determined, using two tempering pistons with integrated thermocouples. To evaluate threshold temperature and time intervals leading to bone necrosis, one piston generated warm temperatures at 49 to 56 °C for 10 s and the other generated cold temperatures at 5 to 1 °C for 30 s. Effects were assessed by a semi-quantitative, histomorphometrical scoring system, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM)., Results: The bone matrix was significantly degenerated starting at 51 °C for 10 s and 5 °C for 30 s. The osteocyte condition indicated significant bone damage beginning at cold temperatures of 2 °C. Temperature inputs starting at 53 °C led to decalcification and swollen mitochondria, which lost the structure of their inner cristae., Conclusions: This study identified temperatures and durations, in both heat and cold, so that the number of samples may be kept low in further studies regarding temperature-induced bone necrosis. Levels of 51 °C for 10 s and 5 °C for 30 s have presented significant matrix degeneration., Clinical Relevance: Temperature thresholds, potentially leading to thermo-explantation of dental implants and other osseointegrated devices, were identified.

Augmentation of alveolar ridge defects is a technique-sensitive procedure in dental implantology. Depending on the size of the defect, it may be necessary to use autogenous bone blocks. However, patients may be against these blocks as these procedures are surgically invasive., Case report: This report describes the restoration of a partially edentulous mandible, which suffered a major bone defect from the right canine to the third molar site after multiple implant losses. The use of a CAD/CAM allogeneic cancellous bone block from a living donor bone was planned for the reconstruction of the alveolar ridge at the defected site. A CBCT scan was taken and the virtual planning of the bone augmentation and placement of four implants was performed. The milled bone block was fixed for augmentation and the implants were placed using a CBCT-generated surgical guide. After osseointegration, a CAD/CAM-fabricated screw-retained metal-ceramic implant fixed partial denture with angulated screw channels was delivered., Results: The use of CAD/CAM-milled, allogeneic bone block resulted in a time-efficient and simplified reconstruction of the defect because no donor site was used, and the fit of the block on the native bone was uneventful and fast. At the 1-year follow-up, an average peri-implant vertical soft tissue decrease of 1&nbsp;mm on buccal and 0.3&nbsp;mm on lingual sites was observed and the peri-implant tissues were healthy., Conclusions: The long-term success of this CAD/CAM cancellous bone block needs to be evaluated in well-designed clinical studies.

Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications.

A successful strategy to enhance the in vivo survival of engineered tissues would be to prevascularize them. In this study, fabricated silk fibroin scaffolds from mulberry and non-mulberry silkworms are investigated and compared for supporting the co-culture of human umbilical vein endothelial cells and human foreskin fibroblasts. Scaffolds are cytocompatible and when combined with fibrin gel support capillary-like structure formation. Density and interconnectivity of the formed structures are found to be better in mulberry scaffolds. ELISA shows that levels of vascular endothelial growth factor (VEGF) released in co-cultures with fibrin gel are significantly higher than in co-cultures without fibrin gel. RT PCR shows an increase in VEGFR2 expression in mulberry scaffolds indicating these scaffolds combined with fibrin provide a suitable microenvironment for the development of capillary-like structures., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Right ventricular remodeling due to pulmonary stenosis increases morbidity in children. Its pathophysiology needs to be clarified., Methods: Six newborn lambs underwent pulmonary arterial banding, seven sham operation. mRNA encoding for cytokines, growth factors and regulators of apoptosis was sequentially measured in myocardium and blood before and up to 12 weeks postoperatively., Results: Experimental animals showed hypertrophy and fibrosis of the right ventricular myocardium, myocardial over-expression of CT-1-mRNA and higher blood concentrations of mRNA encoding for VEGF, TGF-β, Bak and BcL-xL than controls, respectively., Conclusion: Neonatal pulmonary stenosis leads to myocardial hypertrophy that is associated with CT-1 gene expression and with activation of growth- and apoptosis pathways in blood cells.

Purpose: Devices constantly tracking the blood pressure (BP) of hypertensive patients are highly desired to facilitate effective patient management and to reduce hospitalization. We report on experiences gathered in a pilot study that was designed to evaluate the prototype of a newly developed, minimally invasive implantable sensor system for long-term BP monitoring., Methods: The device was implanted in the femoral artery (FA) of 12 sheep via standard FA catheterization under fluoroscopic control. Accuracy of the recorded blood pressure was determined by comparison with a reference catheter, which was positioned in the contralateral FA immediately after implantation. Regular follow-up included angiography, computed tomography (CT), and control of functionality and position of the BP sensor. Animals were euthanized after 6 months. FA segments with in situ pressure sensor underwent macroscopic and histopathologic examinations., Results: All implantations of the novel sensor device in the FA were successful and uneventful. High-quality BP recordings were documented. Bland-Altman plots indicate very good agreement. Comparison with measurements taken from the reference sensor revealed mean differences and standard deviations of -0.56 ± 0.85, 0.29 ± 1.44, and 0.85 ± 2.27 mmHg (diastolic, systolic, and pulse pressure, respectively) after exclusion of one outlier. CT uncovered deficiencies in cable stability that were addressed in a redesign. No thrombus formation, necrosis, or apoptosis were detected., Conclusions: The pilot study proved the technical feasibility of wireless BP measurement in the FA via a novel miniature sensor device.

The differentiation between aseptic loosening and periprosthetic joint infection (PJI) after total joint arthroplasty is essential for successful therapy. A better understanding of pathogenesis of aseptic loosening and PJI may help to prevent or treat these complications. Previous investigations revealed an increased vascularization in the periprosthetic membrane in cases of PJI via PET signals. Based on these findings our hypothesis was that PJI is associated with an increased neovascularization in the periprosthetic membrane. Tissue samples from periprosthetic membranes of the bone-implant interface were investigated histologically for inflammation, wear particles, vascularization and fibrosis. To identify vascular structures antibodies against CD 31, CD 34, factor VIII and CD 105 (endoglin) were applied for immunohistochemical investigations. According to a consensus classification of Morawietz the tissue samples were divided into four types: type I (wear particle induced type, n = 11), type II (infectious type, n = 7), type III (combined type, n = 7) and type IV (indeterminate type, n = 7). Patients with PJI (type II) showed a pronounced infiltration of neutrophil granulocytes in the periprosthetic membrane and an enhanced neovascularization indicated by positive immunoreaction with antibodies against CD 105 (endoglin). Tissue samples classified as type I, type III and type IV showed significantly less immune reaction for CD 105. In cases of aseptic loosening and PJI vascularization is found in different expression in periprosthetic membranes. However, in aseptic loosening, there is nearly no neovascularization with CD 105-positive immune reaction. Therefore, endoglin (CD 105) expression allows for differentiation between aseptic loosening and PJI.

Expression of the pro-angiogenic vascular endothelial growth factor (VEGF) stimulates angiogenesis and correlates with the progression of osteoarthritis. Mechanical joint loading seems to contribute to this cartilage pathology. Cyclic equibiaxial strains of 1% to 16% for 12 h, respectively, induced expression of VEGF in human chondrocytes dose- and frequency-dependently. Stretch-mediated VEGF induction was more prominent in the human chondrocyte cell line C-28/I2 than in primary articular chondrocytes. Twelve hours of 8% stretch induced VEGF expression to 175% of unstrained controls for at least 24 h post stretching, in promoter reporter and enzyme-linked immunosorbent assay (ELISA) studies. High affinity soluble VEGF-receptor, sVEGFR-1/sFlt-1 was less stretch-inducible than its ligand, VEGF-A, in these cells. ELISA assays demonstrated, for the first time, a stretch-mediated suppression of sVEGFR-1 secretion 24 h after stretching. Overall, strained chondrocytes activate their VEGF expression, but in contrast, strain appears to suppress the secretion of the major VEGF decoy receptor (sVEGFR-1/sFlt-1). The latter may deplete a biologically relevant feedback regulation to inhibit destructive angiogenesis in articular cartilage. Our data suggest that mechanical stretch can induce morphological changes in human chondrocytes in vitro. More importantly, it induces disturbed VEGF signaling, providing a molecular mechanism for a stress-induced increase in angiogenesis in cartilage pathologies.

Objectives: A vascular supply network is essential in engineered tissues >100-200-μm thickness. To control vascular network formation in vitro, we hypothesize that capillarization can be achieved locally by using fibers to position and guide vessel-forming endothelial cells within a three-dimensional (3D) matrix., Materials and Methods: Biofunctionalization of poly-(L-lactic acid) (PLLA) fibers was performed by amino-functionalization and covalent binding of RGD peptides. Human foreskin fibroblasts (HFFs) and human umbilical vein endothelial cells (HUVECs) were seeded on the fibers in a mould and subsequently embedded in fibrin gel. After 9-21 days of coculture, constructs were fixed and immunostained (PECAM-1). Capillary-like structures with lumen in the 3D fibrin matrix were verified and quantified using two-photon microscopy and image analysis software., Results: Capillary-like networks with lumen formed adjacent to the PLLA fibers. Increased cell numbers were observed to attach to RGD-functionalized fibers, resulting in enhanced formation of capillary-like structures. Cocultivation of HFFs sufficiently supported HUVECs in the formation of capillary-like structures, which persisted for at least 21 days of coculture., Conclusions: The guidance of vessel growth within tissue-engineered constructs can be achieved using biofunctionalized PLLA microfibers. Further methods are warranted to perform specified spatial positioning of fibers within 3D formative scaffolds to enhance the applicability of the concept.

Enhanced permeability and retention (EPR) and the (over-) expression of angiogenesis-related surface receptors are key features of tumor blood vessels. As a consequence, EPR-mediated passive and Arg-Gly-Asp (RGD) and Asn-Gly-Arg (NGR) based active tumor targeting have received considerable attention in the last couple of years. Using several different in vivo and ex vivo optical imaging techniques, we here visualized and quantified the benefit of RGD- and NGR-based vascular vs EPR-mediated passive tumor targeting. This was done using ∼ 10 nm sized polymeric nanocarriers, which were either labeled with DY-676 (peptide-modified polymers) or with DY-750 (peptide-free polymers). Upon coinjection into mice bearing both highly leaky CT26 and poorly leaky BxPC3 tumors, it was found that vascular targeting did work, resulting in rapid and efficient early binding to tumor blood vessels, but that over time, passive targeting was significantly more efficient, leading to higher overall levels and to more efficient retention within tumors. Although this situation might be different for larger carrier materials, these insights indicate that caution should be taken not to overestimate the potential of active over passive tumor targeting.

Nontraumatic osteonecrosis of the femoral head is still a challenging problem in orthopedic surgery. It is responsible for 10% of the 500,000 hip replacement surgeries in the USA and affects relatively young, active patients in particular. Main reasons for nontraumatic osteonecrosis are glucocorticoid use, alcoholism, thrombophilia, and hypofibrinolysis (Glueck et al., 1997; Orth and Anagnostakos, 2013). One pathomechanism of steroid-induced osteonecrosis is thought to be impaired blood flow to the femoral head caused by increased thrombus formation and vasoconstriction. To investigate the preventive effect of enoxaparin on steroid-related osteonecrosis, we used male New Zealand white rabbits. Osteonecrosis was induced by methylprednisolone-injection (1 × 20 mg/kg body weight). Control animals were treated with phosphate-buffered saline. Treatment consisted of an injection of 11.7 mg/kg body weight of enoxaparin per day (Clexane) in addition to methylprednisolone. Four weeks after methylprednisolone-injection the animals were sacrificed. Histology (hematoxylin-eosin and Ladewig staining) was performed, and empty lacunae and histological signs of osteonecrosis were quantified. Histomorphometry revealed a significant increase in empty lacunae and necrotic changed osteocytes in glucocorticoid-treated animals as compared with the glucocorticoid- and Clexane-treated animals and with the control group. No significant difference was detected between the glucocorticoid and Clexane group and the control group. This finding suggests that cotreatment with enoxaparin has the potential to prevent steroid-associated osteonecrosis.

This study evaluates a novel adhesive fixation technique to affix cortical bone fragments to osteosynthesis plates using common PMMA cement. This technique utilizes a new amphiphilic bone bonding agent adhering with both hydrophilic bone and hydrophobic PMMA cement. After in vitro biomechanical testing of the bonding strength with explanted bovine and rabbit calvarian bone samples, osteosynthesis plates with screw holes of 1.3 and 1.5 mm were placed on the cranial bone of New Zealand white rabbits and the bond strength of these plates was determined through tension tests. In vitro bond strengths of 19.8-26.5 MPa were obtained. Control samples, prepared without a bone bonding agent, exhibited bone bonding strengths <0.2 MPa. In vivo respective bond strengths at the cranium of the white rabbits were 2.5-4.1 MPa 2 weeks post surgery and 1.9-2.5 MPa 12 weeks after implantation. This new innovative fixation method can be envisioned for cases in which conventional fixation techniques of screws and plates are insufficient or not possible due to the bone or trauma conditions. The observed bonding strengths support implementing this technique in nonload bearing regions, such as the central midface or frontal sinus, facilitating immobilization until bone reunion is complete., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: The prevention of the pericardial adhesions largely accountable for the technical difficulty and risk of injury inherent to resternotomy continues to gain in importance with the increasing frequency of reoperations. The hemostatic sponge TachoSil (Nycomed Austria GmbH, Linz, Austria), has shown promising results in adhesion prevention in several regions of the body. This study was designed to evaluate its effectiveness in the prevention of pericardial adhesions in comparison with the Gore-Tex (W. L. Gore and Assoc, Flagstaff, AZ) surgical membrane and a control., Methods: Twenty-four rabbits were distributed into 3 groups: TachoSil, Gore-Tex, or no barrier agent (control). After median sternotomy and pericardiotomy, the cardial surface was exposed to the aggravating effects of room air, irrigation, and gauze abrasion for one hour. A pericardial defect was created and repaired with one of the barrier agents, or left uncovered (control). Resternotomy was performed after 6 months for the evaluation of adhesion formation., Results: Significantly fewer macroscopic adhesions were observed with TachoSil than Gore-Tex in all regions (p < 0.05) excluding the coronary arteries, where the difference in favor of TachoSil did not achieve significance (0.05< p-value <0.10). TachoSil also demonstrated significantly fewer retrosternal adhesions than the control, as well as a universal non-significant trend of fewer adhesions in all regions. The limited lesions present in the TachoSil group were filmy in nature and removed with blunt dissection relatively easily. No significant differences were found between Gore-Tex and the control. Microscopically, the least pronounced fibrosis formation and inflammatory reaction was detected with TachoSil., Conclusions: TachoSil is effective in the prevention of pericardial adhesions., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)