Christian Siebert

BMP-2 Incorporated in a Tricalcium Phosphate Bone Substitute Enhances Bone Remodeling in Sheep

Bone morphogenetic protein-2 (BMP-2) is a well-known osteoinductive protein, which requires a carrier for local application. As an alternative to the previously described carriers, an in situ hardening, resorbable, and osteoconductive β-tricalcium phosphate cement (TCP) is tested. Trepanation defects in the bovine distal femoral epiphysis are filled with a composite consisting of TCP and 200 μg rhBMP-2 per cm3 TCP, autologous bone graft, pure TCP, or left empty. A radiological follow-up is performed after 7 weeks and 3 months. The sheep are euthanized and bone samples are analyzed by microradiography, histology, and histomorphometry. Microradiography and histology show similar results for pure TCP and the composite. The defects are filled with trabecular bone and newly formed bone is in close contact with the remaining TCP-particles. The majority of the cement is resorbed, in the composite group the amount of remaining cement particles is reduced. Defects treated with autologous bone graft are filled completely, while untreated defects shows only a small amount of bone originating from the rim of the defect. Histomorphometry of the defects treated with pure TCP shows a significantly increased bone content in comparison to defects treated with the composite or autologous bone graft. Analysis of the remaining cement particles shows significantly less cement in the TCP/rhBMP-2 group in comparison to pure TCP. The sum of bone and cement content in the rhBMP-2 group shows amounts comparable to the calcified structures found following autologous bone grafting. The addition of rhBMP-2 to the TCP leads to faster remodeling of the defect comparable to autologous bone graft, while defects treated with pure TCP are not completely remodeled.

Assessment of leech therapy for knee osteoarthritis: A randomized study

Background and purposeu2003Symptomatic treatment of osteoarthritis of the knee with leeches is presently undergoing a renaissance. Previous studies have shown methodical weaknesses. In the present study patients were blinded regarding the treatment, and a control group was included to explore possible differences in various subjective clinical scores and intake of pain medication over time between leech therapy and placebo control. Patients and methodsu2003113 patients with advanced osteoarthritis of the knee were included. The patients were randomized to a single treatment group, group I (single leech application, n = 38), a double treatment group, group II (double application, n = 35), and a control group (n = 40). The second treatment in group II took place after an interval of 4 weeks. The treatment in the control group was simulated with the help of an “artificial leech”. Results were documented with the KOOS and WOMAC scores and also a visual analog scale (VAS) for pain. Changes in the use of pain medication were monitored over 26 weeks. Resultsu2003An improvement in KOOS and WOMAC scores, and also in VAS, was found in all 3 groups following treatment. These improvements were statistically significant for treatment groups I and II during the complete follow-up period. The reduction in individual requirements for pain medication was also statistically significant. The greatest improvement was seen in the group treated twice with the leeches, with a long-term reduction of joint stiffness and improved function in the activities of daily living. Interpretationu2003Leech therapy can reduce symptoms caused by osteoarthritis. Repeated use of the leeches appears to improve the long-term results. We have not determined whether the positive outcome of the leech therapy is caused by active substances released during the leeching, the placebo effect, or the high expectations placed on this unusual treatment form.

Numerical analysis of the groundwater regime in the western Dead Sea escarpment, Israel + West Bank

Water is scarce in the semi-arid to arid regions around the Dead Sea, where water supply mostly relies on restricted groundwater resources. Due to increasing population in this region, the regional aquifer system is exposed to additional stress. This results in the continuous decrease in water level of the adjacent Dead Sea. The interaction of an increasing demand for water due to population growth and the decrease of groundwater resources will intensify in the near future. Thus, the water supply situation could worsen significantly unless sustainable water resource management is conducted. In this study, we develop a regional groundwater flow model of the eastern and southern Judea Group Aquifer to investigate the groundwater regime in the western Dead Sea drainage basin of Israel and the West Bank. An extensive geological database was developed and consequently a high-resolution structural model was derived. This structural model was the basis for various groundwater flow scenarios. The objective was to capture the spatial heterogeneity of the aquifer system and to apply these results to the southern part of the study area, which has not been studied in detail until now. As a result we analyzed quantitatively the flow regime, the groundwater mass balance and the hydraulic characteristics (hydraulic conductivity and hydraulic head) of the cretaceous aquifer system and calibrated them with PEST. The calibrated groundwater flow model can be used for integrated groundwater water management purposes in the Dead Sea area, especially within the framework of the SUMAR-Project.

Lack of effect on bone healing of injectable BMP-2 augmented hyaluronic acid

IntroductionAutologous bone graft is the gold standard for the filling of large osseous defects. Because of its limited supply and complications such as pain, bleeding or infection, the development of alternative bone substitutes has been the subject of several studies. In clinical practice, the most commonly used bone substitutes are calcium phosphates like hydroxyapatite or tricalcium phosphate. With the aim to improve the osseointegration of these materials, growth factors such as bone morphogenetic protein-2 (BMP-2) have been added. Preferably, an injectable bone substitute should be made available. Hyaluronic acid is a component of the extracellular matrix of many tissues, including bone. We examined the bone regenerative effect of commercially available, injectable hyaluronic acid (Hyalart®) with and without addition of bone morphogenetic protein-2 (BMP-2).Materials and methodsTrepanation defects of 9.4xa0mm diameter in the intercondylar groove of sheep femora were filled with pure and augmented (200xa0μg BMP-2) hyaluronic acid. As controls, empty defects and defects treated with autologous bone graft harvested from the contralateral side were used. After 3xa0months, the defects were analysed by fluorescence microscopy after intravital fluorescence staining, contact microradiography, histology and histomorphometry.ResultsTreatment of the defects with loaded and unloaded hyaluronic acid resulted in a significant lack of bone formation inside the defects. Untreated defects showed an amount of 5.1% newly formed bone, and defects treated with autologous bone graft revealed a bone content of 20%. The difference between both groups was statistically significant (Pxa0<xa00.05). Furthermore, there was neither a remarkable effect in the periphery of the defects nor ectopic bone formation.ConclusionThe application of the used injectable hyaluronic acid (Hyalart®) with and without BMP-2 is not advantageous as sole bone substitute for the filling of osseous defects.

How to store autologous bone graft perioperatively: an in vitro study

IntroductionAutologous bone graft is the golden standard for bone grafting, but little is known about the influence of various preservation techniques used during surgery immediately following harvest on the osseous structures and graft vitality. Several studies focussed on the optimal treatment of the bone during harvest and implantation, but only few examined the intraoperative storage conditions on the back table. The aim of our study was to examine the influence of various intraoperative preservation techniques on human cancellous bone at different points to optimize the storage during surgery.Materials and methodsCancellous bone was harvested during hip arthroplasty and stored for 2 and 4xa0h under dry conditions, inside a swab moistened with saline solution or in saline solution, 5% glucose solution or culture medium. After the storage period, the bone was cultured and examined 7xa0days after the first cells grew out in one of these groups. Following the identification of the cells as osteoblast-like cells, the cultures were analysed by fluorescence staining, cell count and the XTT-test.ResultsFluorescence staining revealed no avital cells in all groups. Dry storage of the bone led to significantly lower cell metabolism after 2xa0h compared to saline solution and 5% glucose solution. The same was true after 4xa0h dry storage compared to the moistened swab, and glucose and culture medium. Cell count was significantly lower after 2xa0h of dry storage compared to saline solution and culture medium.ConclusionsPerioperative storage of cancellous bone under dry conditions should be avoided. The bone graft should be stored in saline or 5% glucose solution or a moistened swab.

Application of the water balance model J2000 to estimate groundwater recharge in a semi-arid environment: a case study in the Zarqa River catchment, NW-Jordan

Pollution and overexploitation of scarce groundwater resources is a serious problem in the Zarqa River catchment, Jordan. To estimate this resource’s potential, the amount and spatial distribution of groundwater recharge was calculated by applying the hydrological model J2000. The simulation period is composed of daily values gathered over a 30-year period (July 1977 to June 2007). The figure finally obtained for estimated groundwater recharge of the Zarqa River catchment is 105xa0×xa0106xa0m3 per year (21xa0mm a−1). This is 19xa0% higher than the value previously assumed to be correct by most Jordanian authorities. The average ratio of precipitation to groundwater recharge is 9.5xa0%. To directly validate modelled groundwater recharge, two independent methods were applied in spring catchments: (1) alteration of stable isotope signatures (δ18O, δ2H) between precipitation and groundwater and (2) the chloride mass balance method. Recharge rates determined by isotopic investigations are 25xa0% higher, and recharge rates determined by chloride mass balance are 9xa0% higher than the modelled results for the corresponding headwater catchments. This suggests a reasonably modelled safe yield estimation of groundwater resources.

Challenges to estimate surface- and groundwater flow in arid regions: the Dead Sea catchment.

The overall aim of the this study, which was conducted within the framework of the multilateral IWRM project SUMAR, was to expand the scientific basement to quantify surface- and groundwater fluxes towards the hypersaline Dead Sea. The flux significance for the arid vicinity around the Dead Sea is decisive not only for a sustainable management in terms of water availability for future generations but also for the resilience of the unique ecosystems along its coast. Coping with different challenges interdisciplinary methods like (i) hydrogeochemical fingerprinting, (ii) satellite and airborne-based thermal remote sensing, (iii) direct measurement with gauging station in ephemeral wadis and a first multilateral gauging station at the river Jordan, (iv) hydro-bio-geochemical approach at submarine and shore springs along the Dead Sea and (v) hydro(geo)logical modelling contributed to the overall aim. As primary results, we deduce that the following: (i) Within the drainage basins of the Dead Sea, the total mean annual precipitation amounts to 300 mm a(−1) west and to 179 mm a(−1) east of the lake, respectively. (ii) The total mean annual runoff volumes from side wadis (except the Jordan River) entering the Dead Sea is approximately 58–66 × 10(6) m(3) a(−1) (western wadis: 7–15 × 10(6) m(3) a(−1); eastern wadis: 51 × 10(6) m(3) a(−1)). (iii) The modelled groundwater discharge from the upper Cretaceous aquifers in both flanks of the Dead Sea towards the lake amounts to 177 × 10(6) m(3) a(−1). (iv) An unexpected abundance of life in submarine springs exists, which in turn explains microbial moderated geo-bio-chemical processes in the Dead Sea sediments, affecting the highly variable chemical composition of on- and offshore spring waters.The results of this work show a promising enhancement of describing and modelling the Dead Sea basin as a whole.

Localisation and temporal variability of groundwater discharge into the Dead Sea using thermal satellite data

The semi-arid region of the Dead Sea heavily relies on groundwater resources. This dependence is exacerbated by both population growth and agricultural activities and demands a sustainable groundwater management. Yet, information on groundwater discharge as one main component for a sustainable management varies significantly in this area. Moreover, discharge locations, volume and temporal variability are still only partly known. A multi-temporal thermal satellite approach is applied to localise and semi-quantitatively assess groundwater discharge along the entire coastline. The authors use 100 Landsat ETMxa0+xa0band 6.2 data, spanning the years between 2000 and 2011. In the first instance, raw data are transformed to sea surface temperature (SST). To account for groundwater intermittency and to provide a seasonally independent data set ∆T (maximum SST range) per-pixel within biennial periods is calculated subsequently. Groundwater affected areas (GAA) are characterised by ∆Txa0<xa08.5xa0°C. Unaffected areas exhibit values >10xa0°C. This allows the exact identification of 37 discharge locations (clusters) along the entire Dead Sea coast, which spatially correspond to available in situ discharge observations. Tracking the GAA extents as a direct indicator of groundwater discharge volume over time reveals (1) a temporal variability correspondence between GAA extents and recharge amounts, (2) the reported rigid ratios of discharge volumes between different spring areas not to be valid for all years considering the total discharge, (3) a certain variability in discharge locations as a consequence of the Dead Sea level drop, and finally (4) the assumed flushing effect of old Dead Sea brines from the sedimentary body to have occurred at least during the two series of 2000–2001 and 2010–2011.

New perspectives on interdisciplinary earth science at the Dead Sea: The DESERVE project.

The Dead Sea region has faced substantial environmental challenges in recent decades, including water resource scarcity, ~1m annual decreases in the water level, sinkhole development, ascending-brine freshwater pollution, and seismic disturbance risks. Natural processes are significantly affected by human interference as well as by climate change and tectonic developments over the long term. To get a deep understanding of processes and their interactions, innovative scientific approaches that integrate disciplinary research and education are required. The research project DESERVE (Helmholtz Virtual Institute Dead Sea Research Venue) addresses these challenges in an interdisciplinary approach that includes geophysics, hydrology, and meteorology. The project is implemented by a consortium of scientific institutions in neighboring countries of the Dead Sea (Israel, Jordan, Palestine Territories) and participating German Helmholtz Centres (KIT, GFZ, UFZ). A new monitoring network of meteorological, hydrological, and seismic/geodynamic stations has been established, and extensive field research and numerical simulations have been undertaken. For the first time, innovative measurement and modeling techniques have been applied to the extreme conditions of the Dead Sea and its surroundings. The preliminary results show the potential of these methods. First time ever performed eddy covariance measurements give insight into the governing factors of Dead Sea evaporation. High-resolution bathymetric investigations reveal a strong correlation between submarine springs and neo-tectonic patterns. Based on detailed studies of stratigraphy and borehole information, the extension of the subsurface drainage basin of the Dead Sea is now reliably estimated. Originality has been achieved in monitoring flash floods in an arid basin at its outlet and simultaneously in tributaries, supplemented by spatio-temporal rainfall data. Low-altitude, high resolution photogrammetry, allied to satellite image analysis and to geophysical surveys (e.g. shear-wave reflections) has enabled a more detailed characterization of sinkhole morphology and temporal development and the possible subsurface controls thereon. All the above listed efforts and scientific results take place with the interdisciplinary education of young scientists. They are invited to attend joint thematic workshops and winter schools as well as to participate in field experiments.

Sediment fingerprinting in northern Jordan: element-specific correction factors in a carbonatic setting

PurposeWater reservoirs around the world suffer from accelerated sediment loads and, consequently, contamination. Notably, in water-scarce regions such as Jordan, this poses a threat to an important water source, and identifying the sediment sources is an important task. Thus, a sediment fingerprinting study in the Wadi Al-Arab catchment of northern Jordan was implemented with special attention directed to the development of suitable correction factors necessary to improve the comparability of source and sink sediments. The selection of seven conservative elements for the sediment fingerprinting was made, with specific attention directed to the chemical environment of the reservoir.Materials and methodsThirty-six samples from six different surface and subsurface sources and 38 sink samples from the Wadi Al-Arab reservoir were collected. In total, 27 organic and inorganic elements as well as radionuclides were analysed. Two vertical physicochemical water profiles provided information on the pH and Eh conditions and common element concentrations. The stepwise multiple regression analysis model (SMRAM) was developed to explore parameters that influence the element concentrations and their interrelations, and to calculate an element-specific correction factor. The standard selection procedure was expanded by the comparison of water and sink sediment element concentrations, a literature review concerning the pH and Eh conditions and, in selected cases, a correlation analysis.Results and discussionThe combination of Al, Cr, Mn, Fe, 232Th, 228Th and 137Cs provided the best source discrimination, and based on Monte Carlo simulations, the mixing model revealed the existence of three major sediment source areas. These are as follows: (i) olive orchards on slopes, which delivered 59u2009±u20098xa0% of the sediments in the sink; (ii) cultivated fields on plateau and saddle positions contributed 11u2009±u20099xa0%; and (iii) slopes with natural vegetation used for grazing contributed 29u2009±u200915xa0% of the deposited sediment. With a mean residual error of 1.04xa0%, the sum of the source concentrations differs only slightly from sink concentrations and proves that the model is reliable.ConclusionsThe SMRAM model revealed that the different inorganic (total inorganic carbon, TIC) and organic (total organic carbon, TOC) carbon contents and the clay/sand content influence the element concentrations of the sediment samples. Due to the carbonatic environment, it was mainly necessary to correct for TIC. Applying an expanded literature review regarding the chemical environment under investigation, in addition to the standard mass conservation and Kruskal-Wallis test, prevented possible non-conservative elements from entering the discriminant analysis.