Lack of obvious influence of PLLA nanofibers on the gene expression of BMP-2 and VEGF during growth and differentiation of human mesenchymal stem cells.

Growth factors like bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid) (PLLA) nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC) differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2-enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers.

Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells.

The majority of chronic phase chronic myeloid leukemia (CML) patients treated with the tyrosine kinase inhibitor (TKI) imatinib mesylate maintain durable responses to the drug. However, most patients relapse after withdrawal of imatinib and advanced stage patients often develop drug resistance. As CML is considered a hematopoietic stem cell cancer, it has been postulated that inherent protective mechanisms lead to relapse in patients. The ATP binding-cassette transporters ABCB1 (MDR-1; P-glycoprotein) and ABCG2 are highly expressed on primitive hematopoietic stem cells (HSCs) and have been shown to interact with TKIs. Herein we demonstrate a dose-dependent, reversible inhibition of ABCG2-mediated Hoechst 33342 dye efflux in primary human and murine HSC by both imatinib and nilotinib (AMN107), a novel aminopyrimidine inhibitor of BCR-ABL. ABCG2-transduced K562 cells were protected from imatinib and nilotinib-mediated cell death and from downregulation of P-CRKL. Moreover, photoaffinity labeling revealed interaction of both TKIs with ABCG2 at the substrate binding sites as they compete with the binding of [(125)I] IAAP and also stimulate the transporter's ATPase activity. Therefore, our evidence suggests for the role of ABC transporters in resistance to TKI on primitive HSCs and CML stem cells and provides a rationale how TKI resistance can be overcome in vivo.

Thoracic herniation after lumbar spine fusion.

We report on a 65-year-old male patient with rapid onset of incomplete paraparesis, based on a massive thoracic herniation following adjacent instability of the thoracolumbar spine after lumbar fusions with transpedicular instrumentation.

[Design and first clinical results with the ZMR taper revision prosthesis]. / Design und erste klinische Ergebnisse mit dem ZMR-Taper-Revisionsschaft.

AIM: The purpose of this study was to survey and to evaluate the first clinical and radiological results with the cementless ZMR taper hip prosthesis. METHOD: The modular distal-tapered stem was designed with a roughened titanium surface and sharp splines to achieve secure distal fixation and rotational stability. 90 ZMR taper hip prostheses were implanted between October 1999 and July 2002. Out of these, 4 interventions were primary and 86 were revision procedures. In 43 cases a complete hip prosthesis revision and in 43 cases a stem revision was necessary. The mean age of the 90 patients (42 males, 48 females) was 67.1 years. The mean follow-up period was 7.6 months (3 to 25 months). RESULTS: The stem displayed an excellent distal fixation. The mean subsidence could be measured with 4.3 mm. Furthermore, most cases showed a particularly favourable remodelling of the proximal femoral bone stock. Complications associated with revision included intraoperatively 4 femur fractures, 3 femur fissures, 5 femur perforations, 2 trochanter fractures and postoperatively 19 dislocations, 5 superficial wound infections, 2 transient palsies, 1 pulmonary embolism, 1 stem rotation and 4 wound healing failures. Considering these complications 15 re-revisions were necessary and the ZMR taper hip prosthesis had to be exchanged in 3 cases. CONCLUSION: On the one hand the ZMR taper hip prosthesis proved its value, particularly with regard to the stem modularity, the excellent distal fixation in conjunction with the possibility of partial body weight bearing and the rapid bone remodelling of the femur. On the other hand an increased number of postoperative complications and re-revisions occurred. Further long-term studies seem to be essential.

[Electrospun poly-l-lactide nanofibres as scaffolds for tissue engineering]. / Elektrogesponnene Poly-L-Laktid-Nanofasern als resorbierbare Matrix für Tissue-Engineering.

Tissue engineering is a promising tool for treating structural and functional defects in bone and cartilage. To provide optimal conditions for three-dimensional cell growth the use of a scaffold is necessary. The aim of the study was to test the potential application of an electrospun poly (l-lactide)-nanostructured scaffold as a matrix for tissue engineering. Matrices were seeded with human osteosarcoma MG-63 cells and cultivated for 14 days. Cells showed a clear preference for growth along the nanofibres, and demonstrated no signs of degeneration or apoptosis. The fine structure of electrospun nanofibres makes them an ideal scaffold for tissue engineering, in particular for cartilage repair. They can be "doped" with growth factors, medications, etc., and are both biocompatible and biodegradable.

[In vitro long-term culture of human bone under physiological load conditions]. / In vitro Langzeitkultur von humanem Knochen unter physiologischen Lastbedingungen.

There is evidence that mechanical loading is an important, if not the most important factor influencing bone mass and architecture. Investigations under in vivo conditions and cell culture methods, performed during the last years, helped to elucidate these mechanisms. However, the mechanisms by which load bearing acts on bone tissue are until now not completely understood. It is well accepted that weight-bearing exercise increases bone mass and on the other hand lower physical activity engenders bone loss. But neither a physiological threshold for bone loss or bone growth nor the character of the mechanical stimulus concerning amount, frequency and duration of the applied load are known. Even more speculative is the idea how this signal is transformed into the biological response of growing bone. Three-dimensional bone-culture-systems with simultaneous applied mechanical load enables to improve the knowledge of regulation of bone metabolism. We show the results of a long-term in vitro experiment with human cancellous bone under physiological load conditions.

[Systematic analysis of ground reaction forces before and after hip and knee arthroplasty]. / Systematische Analyse der Anderung der Bodenreaktionskräfte bei Hüft- und Kniearthrose prä- und postoperativ.

In this prospective study we employed a newly developed gait analysis system to compare the ground reaction force patterns in 15 patients before and after total hip or knee replacement. In this system, data are measured separately for each limb. Measured data were also obtained from 30 healthy adults and compared with those obtained from the patient group. We analysed the three-dimensional force patterns, impulse, frequency, stride and double stance, and compared changes in the postoperative gait patterns. The vertical force maxima Fy identify the peak forces obtaining during walking. The results showed significantly increased (p < 0.05) postoperative force maxima Fy2 and Fy3 for both knee replacement (Fy2: 82.48 to 86.17 and Fy3: 96.09 to 99.35% body weight, pre- and postoperatively, respectively) and hip replacement (Fy2: 84.44 to 88.08 and Fy3: 98.63 to 101.96% body weight, pre- and postoperatively, respectively). The ADAL system proved suitable for the easy performance of gait analysis, and thus may be of future value in the area of clinical quality assurance.

A comparative clinical outcome evaluation of smooth (10-13 year results) versus rough surface finish (5-8 year results) in an otherwise identically designed cemented titanium alloy stem.

BACKGROUND: We retrospectively compared the influence of surface finish with respect to the long-term durability of a cemented titanium alloy stem of the same design but different surface finish. METHODS: From 1984 to 1994, the stem was made of a titanium-aluminum-vanadium alloy. A total of 201 patients with 220 smooth stems (mean follow-up 11 years and 4 months) out of 612 implanted between 1984 and 1987 and 319 patients with 343 rough stems (mean follow-up 5 years and 10 months) out of 812 implanted between 1991 and 1993 could be reviewed clinically and radiologically for comparison. The average age of the patients with the smooth stem was 58.1 years and of the patients with the rough stem, 62.2 years. In both groups, 35% of patients were male and 65% female. RESULTS: The mean Merle d'Aubigné hip score increased from 10.5 to 16.0 points in the smooth stem group and from 11.0 to 16.9 points in the rough stem group. The distribution of radiolucent lines, according to the zones of Gruen, was similar in both groups. The smooth stem required revision in 18 cases after a mean follow-up of 11 years and 4 months and the rough stem in 30 cases after a mean follow-up of 5 years and 10 months. The survival analysis (Kaplan-Meier) revealed 95.4% survival after 13 years for the smooth femoral component and 76.7% survival after 8 years for the rough femoral component. CONCLUSIONS: The implantation of titanium alloy stems with a rough surface finish cannot be recommended because of its high aseptic loosening rate.

[10 years results with a Monobloc hip endoprosthesis cup with multilayer titanium mesh coating for cement-free implantation]. / 10-Jahres-Ergebnisse einer Monobloc-Hüftendoprothesenpfanne mit mehrlagiger Reintitangitterschale zur zementfreien Implantation.

PURPOSE: Can a cementless hemispheric acetabular component which is made of ultra-high-density polyethylene (UHMW-PE) and a heat-bounded porous titanium mesh coating be recommended 10 years after implantation? METHODS: Between 1986 and 1988, 279 total hip arthroplasties in which the cementless socket had been used were performed in 261 patients. The results of 145 patients with 159 hip sockets (55.5%) were reviewed clinically and radiologically for comparison after a minimum of 10 years. The clinical and radiological re-examination was documented in a standardized questionnaire in which several scores were integrated. All X-rays were stored and analysed by a special hardware and software computer system. RESULTS: The mean age of the female patients (n = 85) was 63.1 years and of the male patients (n = 60) 60.9 years. The mean follow-up period was 10 years and 3 months. The Merle d'Aubigné hip score increased from 10.9 to 16.5 points at the follow-up evaluation. Radiolucent lines and cysts according to the zones of DeLee/Charnley were seen only in 2% of all cases. The mean polyethylene wear (head disarrangement) was measured with 1.79 mm after 10 years and 1.92 mm after 11 years. In total, 16 revisions (5.7%), 13 (4.6%) aseptic and 3 (1.1%) septic, out of 279 implanted sokets had to be performed. In particular, the acetabular cup with a diameter of 48 mm demonstrated a high loosening rate (4 of 9). The 10-year survival analysis (Kaplan-Meler) was measured with 92.8%. CONCLUSION: Our results with a cementless socket with titanium mesh coating show insignificant radiolucent lines and an exceptional high 10-year survivorship in which the particular implant philosophy is of great importance for the long-term success. In conclusion, the acetabular component can be recommended for further implantation.

Size and direction of hip joint forces associated with various positions of the acetabulum.

When total hip replacement is performed, the position of the acetabular component may affect wear and component survival time. We considered the questions: In what way does displacement of the hip joint center alter (1) the magnitude and (2) the direction of the resultant force? Biomechanical tests were carried out on a human multibody model. After displacement of the hip joint center, the resultant forces were calculated for the single leg stance. With the flexed single leg stance, maximum hip joint forces were observed with lateral, cranial, posterior displacement. The peak forces were affected by the modeling of a gluteus maximus wrapping point at the ischial tuberosity and were overestimated when this was removed. With the straight single leg stance, posterior displacement decreases the total load on the hip joint because of the increased leverage of the rectus femoris. With regard to the direction of the resultant force, medial displacement increases the angles in both planes, cranial displacement increases it in the sagittal plane (cranial, posterior-caudal, anterior), and anterior displacement decreases the angle in the sagittal plane and increases it in the frontal plane (medial, cranial-lateral, caudal). The direction of the force is relatively insensitive to displacement of the hip joint center. The results presented here indicate a marked increase in the force after lateral, cranial, posterior displacement of the center in the flexed single leg stance. To avoid extreme joint loading and to reduce the wear after total hip arthroplasty, the cranial and posterior regions of the acetabulum should be fully reconstructed. A high hip joint center has an adverse effect on the magnitude of the force, although the directions are hardly affected by it.

[10 year results with a cemented fine-grit-blasted titanium-aluminum-vanadium hip endoprosthesis shaft]. / 10-Jahres-Ergebnisse mit einem zementierten feingestrahlten Titan-Aluminium-Vanadium-Hüftendoprothesenschaft.

PURPOSE: Are the results of cemented titanium hip arthroplasty as bad as described in literature? We present the 10-year results of a cemented mild grid blasted Titanium-Aluminium-Vanadium Stem in Total-Hip-Arthroplasty. METHODS: The clinical and radiological reexamination was documented in standardized questionnaire in which several scores were integrated. All X-rays were stored and analysed by a special hardware and software computer system. RESULTS: 35% of all patients could be reexamined both clinically and roentgenologically. 71 patients were male (mean age 56.1 years) and 130 female (mean age 59.3 years). The average follow-up period was 11 years and 4 months. The mean Merle d'Aubigné hip score increased from 10.5 to 16.0 points at the follow-up evaluation. Radiolucent lines were according to the zones of Gruen seen in 1% to 22% depending on the zone and the size of the femoral component. 18 reoperations of the femoral component (2.9%) had to be performed. The survivorship analysis (Kaplan-Meier) showed a 95.4% survival of the femoral component after 10 years. CONCLUSION: Our findings with a cemented mild grid blasted Titanium-Aluminum-Vanadium stem demonstrate excellent results unlike it was reported for cemented femoral components of similar alloy but different design and cementation philosophy.