[Show abstract][Hide abstract] ABSTRACT: Objectives: A vascular supply network is essential in engineered tissues greater than 100-200µm thickness. To control vascular network formation in vitro, we hypothesise that capillarisation can be achieved locally by using fibres to position and guide vessel-forming endothelial cells within a 3D matrix. Material and Methods: Biofunctionalisation of poly-(L-lactic acid) (PLLA) fibres was performed by amino-functionalisation and covalent binding of RGD-peptides. Human foreskin fibroblasts (HFFs) and human umbilical vein endothelial cells (HUVECs) were seeded on the fibres in a mould and subsequently embedded in fibrin gel. After 9-21 days of co-culture, constructs were fixed and immunostained (CD31). 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 fibres. Increased cell numbers were observed to attach to RGD-functionalised fibres, resulting in enhanced formation of capillary-like structures. Co-cultivation of HFFs sufficiently supported HUVECs in the formation of capillary-like structures, which persisted for at least 21 days of co-culture. Conclusions: The guidance of vessel growth within tissue-engineered constructs can be achieved using biofunctionalised PLLA microfibres. Further methods are warranted to perform specified spatial positioning of fibres within 3D formative scaffolds to enhance the applicability of the concept.
Tissue Engineering Part A 01/2014; · 4.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
The Annals of thoracic surgery 10/2012; · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: In the immunohistochemical analysis of tissue-engineered structures, aggressive treatments for fixation and antigen retrieval can impair the quality of specimen staining and visualization. Hypothesis: We hypothesized that the adequate choice of fixative and antigen-retrieval method might improve the quality of immunohistochemical staining. Methods: Tissue-engineered vascular grafts were fixed using formalin, Carnoy's, or HOPE(®) fixative. Antigen retrieval was performed where necessary and samples from each group were stained using hematoxylin and eosin to assess overall tissue preservation. For a set of proteins relevant to cardiovascular tissue development, immunohistochemical staining was applied to formalin-, Carnoy's-, and HOPE-fixed specimens to allow a comparative analysis. Results: In tissue-engineered constructs, antigen retrieval methods necessary after formalin fixation led to significant destruction of the overall tissue structure. Carnoy's fixation resulted in good overall tissue preservation and adequate results for immunohistochemical staining of alpha-smooth muscle actin (α-SMA), vimentin, type I collagen, elastin, and laminin. HOPE fixative led to a loosened tissue structure and a swollen appearance but showed adequate results for staining against type III collagen and elastin. Formalin fixation without antigen retrieval led to inadequate visualization of α-SMA, vimentin, type I- and type III collagen, and laminin. Conclusion: Based on the present study, we recommend that Carnoy's fixative is employed for the preservation of tissue-engineered constructs to allow immunohistochemical analysis of type I- and type III collagen, elastin, laminin, α-SMA, and vimentin. However, it is clear that the technique requires optimization based on the particular tissue engineering application.
Tissue Engineering Part C Methods 06/2012; · 4.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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®.
Journal of Biomaterials Applications 03/2010; 25(7):721-41. · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The AIM of this prospective study was to identify a typical pattern for fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography (PET) to differentiate aseptic loosening (tibial and / or femoral component) from prosthesis infection in painful knee prosthesis.
20 patients with painful knee prosthesis underwent PET imaging to evaluate aseptic loosening / prosthesis infection of their knee prosthesis. The interface between bone and surrounding soft tissue or bone was divided into 3 segments each for both the femur and the tibia and in addition for 4 segments reflecting the surrounding periprosthetic soft tissue. FDG uptake in each of the segments was scored (0-3) by two independent observers. The final diagnosis was based on operative findings with subsequent microbiological culture and histological examination.
After surgical revision 6 femoral components and 5 tibial components were found to be loose and prosthetic infection was present in 9 prostheses. In 8 of 9 infected prostheses loosening of the femoral und tibial component occurred. There was no statistically significant correlation between the standardised uptake within each of the segments and the diagnosis of aseptic loosening or prosthesis infection. A differentiated qualitative and quantitative FDG-PET result interpretation divided into five categories was developed. Specificity / sensitivity / positive predictive value / negative predictive value were 93% / 83% / 83% / 93% for aseptic loosening of the femoral component, 87% / 80% / 67% / 93% for aseptic loosening of the tibial component and 82% / 89% / 80% / 90% for infection.
This pilot study shows that FDG-PET is a promising diagnostic tool for patients with painful knee prostheses. There is a good correlation between PET images and the intraoperative and pathology findings. Its clinical value, however, warrants further evaluation in a larger patient population.
[Show abstract][Hide abstract] 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.
Head & Face Medicine 07/2009; 5:13. · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Among the different graft materials being applied in sinus elevation surgery autogenous bone, especially from the iliac crest, is considered to be the graft of choice. The goal of this prospective study was to investigate whether purely cancellous transplants of this donor site lead to significantly better results regarding bone quantity and quality when compared to corticocancellous iliac bone grafts.
Fifteen patients suffering from extreme maxillary atrophy underwent bilateral sinus floor augmentation with grafts from the iliac crest consisting of purely cancellous bone (PCB) for the right side and a mixture of 50% cancellous and 50% cortical bone for the left side, respectively. Bone samples that were taken during implant insertion were examined histologically for semiquantitative assessment. In addition, bone density was measured histomorphometrically. Data were statistically analyzed by a repeated measures analysis of covariance model and post hoc paired t-tests as well as Pearson's correlation analysis.
Semiquantitative analysis of bone quality resulted in comparable results for both graft preparations while bone density was significantly higher in the PCB group. Without consideration of the different transplant groups, there was neither a significant correlation between patients' age and bone density nor bone quality. Differences between the genders could not be observed either.
Because of better bone density, the PCB graft from the iliac crest remains our gold standard. Even in elderly patients, autogenous grafts can be utilized without losses in the properties of the resulting bone.
Clinical Oral Implants Research 01/2009; 20(2):109-15. · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Archives of Orthopaedic and Trauma Surgery 08/2008; 128(7):701-7. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As a clinical pilot study using the skeletonized, periodontally/miniscrew-anchored Distal Jet appliance, this study aimed to verify the positional stability of the palatally-inserted paramedian miniscrews when subjected to loading for several months, hence to assess the efficacy of the supporting anchorage design.
Sixteen miniscrews (8-9 mm in length, 1.6 mm in diameter, polished surface) were inserted in the anterior region of the palate at paramedian locations. Once they had been in place for 1 week, skeletonized Distal Jets for bilateral molar distalization were anchored to the first premolars and necks of the miniscrews using composite. The appliances' coil spring systems were activated to a distalization force of 200-240 cN. The miniscrews were processed histologically after minimally-invasive explantation.
Forces acting reciprocally on the anchorage unit result in significant anchorage loss in the palatally-inserted titanium miniscrews used for added anchorage support: we observed ventral movement in the vicinity of the miniscrew heads of 0.95+/-0.82 mm (the mean; p = 0.005), and extrusion of 0.21+/-0.28 mm (p = 0.040). In the process they tipped 2.65 degrees +/-6.23 degrees in relation to the palatal plane and 2.15 degrees +/-5.76 degrees in relation to the anterior cranial base. We observed no evidence of direct screw-to-bone contact in any of the explanted miniscrews.
Titanium miniscrews with a polished surface, 1.6 mm in diameter and 8-9 mm long, do not provide stationary anchorage in molar distalization with the periodontally/miniscrew-anchored Distal Jet. When subjected for several months to load from forces that act in reciprocity to the force systems occurring during molar distalization, they fail to remain completely stationary in position in the palatal locations in which they were inserted. However, the combined anchorage setup is sufficient, intraorally and regardless of patient compliance, to largely compensate for the mesially-acting forces that occur reciprocal to molar distalization.
Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie 04/2008; 69(2):110-20. · 0.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We give the first account of failure of extracorporeal membrane oxygenation therapy secondary to congenital cystic malformation of the lung (CCAM) type 0.
Pediatric intensive care unit.
A female neonate, appropriate for gestational age, with respiratory failure immediately after delivery.
: Cardiopulmonary support with venoarterial extracorporeal membrane oxygenation.
There was no improvement of pulmonary function, and the patient died. CCAM type 0 was diagnosed postmortem.
CCAM type 0 should be considered as a rare differential diagnosis of irreversible lung pathologies leading to failure of extracorporeal membrane oxygenation therapy for neonatal respiratory failure.
Pediatric Critical Care Medicine 12/2007; 8(6):580-1. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cemented revision of femoral components in total hip arthroplasty has shown high rates of early loosening due to reduced micro- and macroretention of the cement to the endostal bone stock. Enhanced stability can be reached by an amphiphilic bonder, which offers a covalent bonding of the hydrophobic cement to the hydrophilic bone. The aim of this study is to evaluate the biocompatibility of such a bonder and its effects on the mechanical stability of cemented hip arthroplasty stems in vivo.
Total cemented hip arthroplasties were performed in 20 sheep. In the verum group (n = 10) the implant bed was preconditioned by application of the bonder prior to femoral stem implantation. To study the biocompatibility around the bone-cement interface fluorescent marking of osteoblasts was applied in vivo throughout the observation period of 9 months. Native X-rays of the hip joints were obtained immediately after implantation and after euthanasia. The bone-cement interface was examined histologically.
All stems of the verum group showed firm bonding of cement to bone in manual testing, while in 7 of the 10 controls the stems with adherent cement could be easily pulled out off the bony implant bed. This was coherent with significantly higher rates of progredient radiolucent lines and soft-tissue interpositions between bone and cement in the control group. The bonder was biocompatible.
When preconditioned with an amphiphilic bonder, cemented stems showed a markedly higher adhesive strength to the cancellous bone without signs of inflammation or neoplasia. This procedure might offer enhanced longevity of cemented femoral revision stems in hip arthroplasty.
[Show abstract][Hide abstract] ABSTRACT: Treatment strategies of cerebral aneurysms include surgical clipping and endovascular therapies. To determine the long-term results of these therapeutic strategies, the vessel wall reaction close to the former aneurysm was studied according to the assumption that an intact endothelial layer over the former aneurysm neck constitutes complete vessel wall reconstruction and stable aneurysm obliteration.
Aneurysms were created in 40 rabbits by intraluminal elastase incubation of the common carotid artery. Five animals each were assigned to the following groups: untreated, porous stents, polyurethane covered stentgrafts, porous stents with subsequent coiling. Ten animals were treated with coils alone, 10 with clips. After 6 months, angiography, histology, and scanning electron microscopy was performed.
Porous stents did not obliterate the aneurysm, whereas stentgrafts did; in-stent stenosis of up to 60% was present because of neointimal multilayer proliferation. After coiling, the aneurysm dome was occluded with fibrinous and collagenous material, whereas the aneurysm neck was not covered by an endothelial lining. Coil loops lay bare within the vessel, with fresh thrombus material on their surface. After clipping, a thin layer of endothelial lining bridging the two attached vessel walls was present, thereby completely obliterating the aneurysm and reconstructing the vessel wall.
This study demonstrates complete and stable aneurysm obliteration with vessel wall reconstruction after clipping, a sufficient obliteration of the aneurysm dome using endovascular techniques, but a failed healing response of the aneurysm neck that might correlate to its associated higher risk of rebleed. Whether or not this is counterbalanced by the better immediate outcome after endovascular treatment remains a matter of debate.
[Show abstract][Hide abstract] ABSTRACT: Epithelioid sarcoma is a rare and highly malignant soft tissue tumor that is commonly found in the extremities and rarely in the trunk area. This malignant tumor often mimics granuloma or nodular fasciitis, which causes a delay in establishing the diagnosis. This type of cancer has a high recurrence rate. Surgical treatment requires wide radical resection. The objective of this case report is to highlight the unique location of a rare neoplasm and to illustrate the relentless course of epithelioid sarcoma despite initial radical resection. A 14-year-old boy was admitted to our facility with a soft tissue mass on the right lower thoracic spine. The large tumor mass had deeply penetrated into the muscles, infiltrated the neuroforamen of T9-T10 level, and compressed the dural sac. Immunohistological study of the biopsy was highly consistent with an epithelioid sarcoma. Wide excision of the mass, laminectomy and spine fusion with instrumentation was performed. The patient received chemotherapy and irradiation. The first recurrence of the neoplasm was seen as a contralateral metastasis 21 months after the resection. On the last follow-up, 3 years postoperatively, the patient was in a good general condition. However, further progression of the sarcoma had to be recognized. Our case encompasses multiple features that represent negative prognostic factors. Initial wide excision of the neoplasm and adjuvant therapy including chemotherapy and irradiation seem to slow down the relentless course of epithelioid sarcoma in the trunk.
[Show abstract][Hide abstract] ABSTRACT: The etiology and the pathogenesis of congenital pseudarthrosis of the tibia (CPT) are still unknown. The affected tibia exhibits insufficient mechanical strength and osteogenetic capability. CPT is frequently associated with neurofibromatosis type 1 (NF1; von Recklinghausen's disease); however, both diseases have not yet been linked pathogenetically. This study presents the pathomorphologic findings of CPT under special consideration of NF1. Therefore, samples from patients operated on for CPT (n = 4) with (n = 3) and without (n = 1) neurofibromatosis were investigated by light microscopy, immunohistochemistry, and electron microscopy. The most striking finding in all patients was thickened periosteum with accumulation of nerval cells surrounding small arteries, causing subtotal or complete obliteration. In conclusion, impaired vascularization can result in decreased osteogenic capabilities. The similarity of ultrastructural findings in the abnormal periosteum and in skin neurofibromas of neurofibromatosis patients may indicate a pathogenetic association of both diseases.
Pathology - Research and Practice 02/2005; 201(4):305-12. · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Congenital aplasia or hypoplasia of the fibula (FAH) is a rare malformation that is defined by a partial or complete absence of the fibular bone. Etiology and pathogenesis are unknown and the precise morphology of the tissue cord replacing the malformed fibula has not been well described. Therefore, tissue cord was examined in 8 patients with FAH. Light microscopic, immunohistochemical, and electron microscopic investigations showed a core of embryonic cartilage with collagen II and VI expressions surrounded by connective tissue. Although collagen II expression is typical for chondroid differentiation, collagen VI reactivity is normally seen in articular cartilage and tendon-like fibrocartilaginous tissue but is absent in hyaline cartilage. Further ultrastructural analyses by electron microscopy supported these findings. The histomorphologic changes correspond to the histologic findings of Papenbrock et al. (2000, Mech Dev 92:113-123) who produced a congenital malformation in transgenic mice that resembled FAH by overexpression of Hox c11.
Pediatric and Developmental Pathology 01/2005; 8(4):474-82. · 0.86 Impact Factor