Tissue engineering bone - reconstruction of critical sized segmental bone defects in a large animal model

Currently, well established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, their application, however, is associated with disadvantages. These include limited access and availability, donor site morbidity and haemorrhage, increased risk of infection, and insufficient transplant integration. As a result, recent research focuses on the development of complementary therapeutic concepts. The field of tissue engineering has emerged as an important alternative approach to bone regeneration. Tissue engineering unites aspects of cellular biology, biomechanical engineering, biomaterial sciences and trauma and orthopaedic surgery. To obtain approval by regulatory bodies for these novel therapeutic concepts the level of therapeutic benefit must be demonstrated rigorously in well characterized, clinically relevant animal models. Therefore, in this PhD project, a reproducible and clinically relevant, ovine, critically sized, high load bearing, tibial defect model was established and characterized as a prerequisite to assess the regenerative potential of a novel treatment concept in vivo involving a medical grade polycaprolactone and tricalciumphosphate based composite scaffold and recombinant human bone morphogenetic proteins.

A microanalytical study of the surfaces of normal, delipidized, and artificially “resurfaced” articular cartilage

The surface amorphous layer of articular cartilage is of primary importance to its load-bearing and lubrication function. This lipid-filled layer is degraded/disrupted or eliminated when cartilage degenerates due to diseases. This article examines further the characteristic of this surface overlay using a combination of microscopy and imaging methods to evaluate the hypothesis that the surface of articular cartilage can be repaired by exposing degraded cartilage to aqueous synthetic lipid mixtures. The preliminary results demonstrate that it is possible to create a new surface layer of phospholipids on the surface of cartilage following artificial lipid removal, but such a layer does not possess enough mechanical strength for physiological function when created with either unsaturated palmitoyloleoyl- phosphatidylcholine or saturated dipalmitoyl-phosphatidylcholine component of joint lipid composition alone. We conclude that this may be due to low structural cohesivity, inadequate time of exposure, and the mix/content of lipid in the incubation environment.

Shear tests of lipped channel beams with stiffened web openings

Cold-formed steel lipped channel beams (LCB) are used extensively in residential, industrial and commercial buildings as load bearing structural elements. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. Past research has shown that the shear capacities of LCBs were reduced by up to 70% due to the inclusion of these web openings. Hence there is a need to improve the shear capacities of LCBs with web openings. A cost effective way of eliminating the detrimental effects of large web openings is to attach suitable stiffeners around the web openings and restore the original shear strength and stiffness of the LCBs. Hence detailed experimental studies were undertaken to investigate the shear behaviour and strength of LCBs with stiffened web openings. Both plate and stud stiffeners with varying sizes and thicknesses were attached to the web elements of LCBs using different screw-fastening arrangements. Simply supported test specimens of LCBs with aspect ratios of 1.0 and 1.5 were loaded at mid-span until failure. Test results showed that the plate stiffeners established using AISI recommendations are inadequate to restore the shear strengths of LCBs with web openings. Hence new stiffener arrangements have been proposed for LCBs based on experimental results. This paper presents the details of this experimental study on the shear strength of lipped channel beams with stiffened web openings, and the results.

Application of high voltage, high frequency pulsed electromagnetic field on cortical bone tissue

Over the last few decades, electric and electromagnetic fields have achieved important role as stimulator and therapeutic facility in biology and medicine. In particular, low magnitude, low frequency, pulsed electromagnetic field has shown significant positive effect on bone fracture healing and some bone diseases treatment. Nevertheless, to date, little attention has been paid to investigate the possible effect of high frequency, high magnitude pulsed electromagnetic field (pulse power) on functional behaviour and biomechanical properties of bone tissue. Bone is a dynamic, complex organ, which is made of bone materials (consisting of organic components, inorganic mineral and water) known as extracellular matrix, and bone cells (live part). The cells give the bone the capability of self-repairing by adapting itself to its mechanical environment. The specific bone material composite comprising of collagen matrix reinforced with mineral apatite provides the bone with particular biomechanical properties in an anisotropic, inhomogeneous structure. This project hypothesized to investigate the possible effect of pulse power signals on cortical bone characteristics through evaluating the fundamental mechanical properties of bone material. A positive buck-boost converter was applied to generate adjustable high voltage, high frequency pulses up to 500 V and 10 kHz. Bone shows distinctive characteristics in different loading mode. Thus, functional behaviour of bone in response to pulse power excitation were elucidated by using three different conventional mechanical tests applying three-point bending load in elastic region, tensile and compressive loading until failure. Flexural stiffness, tensile and compressive strength, hysteresis and total fracture energy were determined as measure of main bone characteristics. To assess bone structure variation due to pulse power excitation in deeper aspect, a supplementary fractographic study was also conducted using scanning electron micrograph from tensile fracture surfaces. Furthermore, a non-destructive ultrasonic technique was applied for determination and comparison of bone elasticity before and after pulse power stimulation. This method provided the ability to evaluate the stiffness of millimetre-sized bone samples in three orthogonal directions. According to the results of non-destructive bending test, the flexural elasticity of cortical bone samples appeared to remain unchanged due to pulse power excitation. Similar results were observed in the bone stiffness for all three orthogonal directions obtained from ultrasonic technique and in the bone stiffness from the compression test. From tensile tests, no significant changes were found in tensile strength and total strain energy absorption of the bone samples exposed to pulse power compared with those of the control samples. Also, the apparent microstructure of the fracture surfaces of PP-exposed samples (including porosity and microcracks diffusion) showed no significant variation due to pulse power stimulation. Nevertheless, the compressive strength and toughness of millimetre-sized samples appeared to increase when the samples were exposed to 66 hours high power pulsed electromagnetic field through screws with small contact cross-section (increasing the pulsed electric field intensity) compare to the control samples. This can show the different load-bearing characteristics of cortical bone tissue in response to pulse power excitation and effectiveness of this type of stimulation on smaller-sized samples. These overall results may address that although, the pulse power stimulation can influence the arrangement or the quality of the collagen network causing the bone strength and toughness augmentation, it apparently did not affect the mineral phase of the cortical bone material. The results also confirmed that the indirect application of high power pulsed electromagnetic field at 500 V and 10 kHz through capacitive coupling method, was athermal and did not damage the bone tissue construction.

Development of zonal cartilage constructs : effects of chondrocyte subpopulation, compressive stimulation, and culture models

Articular cartilage is a highly resilient tissue located at the ends of long bones. It has a zonal structure, which has functional significance in load-bearing. Cartilage does not spontaneously heal itself when damaged, and untreated cartilage lesions or age-related wear often lead to osteoarthritis (OA). OA is a degenerative condition that is highly prevalent, age-associated, and significantly affects patient mobility and quality of life. There is no cure for OA, and patients usually resort to replacing the biological joint with an artificial prosthesis. An alternative approach is to dynamically regenerate damaged or diseased cartilage through cartilage tissue engineering, where cells, materials, and stimuli are combined to form new cartilage. However, despite extensive research, major limitations remain that have prevented the wide-spread application of tissue-engineered cartilage. Critically, there is a dearth of information on whether autologous chondrocytes obtained from OA patients can be used to successfully generate cartilage tissues with structural hierarchy typically found in normal articular cartilage. I aim to address these limitations in this thesis by showing that chondrocyte subpopulations isolated from macroscopically normal areas of the cartilage can be used to engineer stratified cartilage tissues and that compressive loading plays an important role in zone-dependent biosynthesis of these chondrocytes. I first demonstrate that chondrocyte subpopulations from the superficial (S) and middle/deep (MD) zones of OA cartilage are responsive to compressive stimulation in vitro, and that the effect of compression on construct quality is zone-dependent. I also show that compressive stimulation can influence pericelluar matrix production, matrix metalloproteinase secretion, and cytokine expression in zonal chondrocytes in an alginate hydrogel model. Subsequently, I focus on recreating the zonal structure by forming layered constructs using the alginate-released chondrocyte (ARC) method either with or without polymeric scaffolds. Resulting zonal ARC constructs had hyaline morphology, and expressed cartilage matrix molecules such as proteoglycans and collagen type II in both scaffold-free and scaffold-based approaches. Overall, my findings demonstrate that chondrocyte subpopulations obtained from OA joints respond sensitively to compressive stimulation, and are able to form cartilaginous constructs with stratified organization similar to native cartilage using the scaffold-free and scaffold-based ARC technique. The ultimate goal in tissue engineering is to help provide improved treatment options for patients suffering from debilitating conditions such as OA. Further investigations in developing functional cartilage replacement tissues using autologous chondrocytes will bring us a step closer to improving the quality of life for millions of OA patients worldwide.

Near infrared spectroscopy for non-destructive evaluation of articular cartilage

There is a need for an accurate real-time quantitative system that would enhance decision-making in the treatment of osteoarthritis. To achieve this objective, significant research is required that will enable articular cartilage properties to be measured and categorized for health and functionality without the need for laboratory tests involving biopsies for pathological evaluation. Such a system would provide the capability of access to the internal condition of the cartilage matrix and thus extend the vision-based arthroscopy that is currently used beyond the subjective evaluation of surgeons. The system required must be able to non-destructively probe the entire thickness of the cartilage and its immediate subchondral bone layer. In this thesis, near infrared spectroscopy is investigated for the purpose mentioned above. The aim is to relate it to the structure and load bearing properties of the cartilage matrix to the near infrared absorption spectrum and establish functional relationships that will provide objective, quantitative and repeatable categorization of cartilage condition outside the area of visible degradation in a joint. Based on results from traditional mechanical testing, their innovative interpretation and relationship with spectroscopic data, new parameters were developed. These were then evaluated for their consistency in discriminating between healthy viable and degraded cartilage. The mechanical and physico-chemical properties were related to specific regions of the near infrared absorption spectrum that were identified as part of the research conducted for this thesis. The relationships between the tissue's near infrared spectral response and the new parameters were modeled using multivariate statistical techniques based on partial least squares regression (PLSR). With significantly high levels of statistical correlation, the modeled relationships were demonstrated to possess considerable potential in predicting the properties of unknown tissue samples in a quick and non-destructive manner. In order to adapt near infrared spectroscopy for clinical applications, a balance between probe diameter and the number of active transmit-receive optic fibres must be optimized. This was achieved in the course of this research, resulting in an optimal probe configuration that could be adapted for joint tissue evaluation. Furthermore, as a proof-of-concept, a protocol for obtaining the new parameters from the near infrared absorption spectra of cartilage was developed and implemented in a graphical user interface (GUI)-based software, and used to assess cartilage-on-bone samples in vitro. This conceptual implementation has been demonstrated, in part by the individual parametric relationship with the near infrared absorption spectrum, the capacity of the proposed system to facilitate real-time, non-destructive evaluation of cartilage matrix integrity. In summary, the potential of the optical near infrared spectroscopy for evaluating articular cartilage and bone laminate has been demonstrated in this thesis. The approach could have a spin-off for other soft tissues and organs of the body. It builds on the earlier work of the group at QUT, enhancing the near infrared component of the ongoing research on developing a tool for cartilage evaluation that goes beyond visual and subjective methods.

Numerical studies of gypsum plasterboard panels under standard fire conditions

Gypsum plasterboards are commonly used as a fire safety material in the building industry. Many research studies have been undertaken to investigate the thermal behaviour of plasterboards under standard fire conditions. However, there are many discrepancies in relation to the basic thermal properties of plasterboards while simple equations are not available to predict the ambient surface time–temperature profiles of gypsum plasterboard panels that can be used in simulating the behaviour and strength of steel studs or joists in load bearing LSF wall and floor systems. In this research, suitable thermal properties of plasterboards were proposed based on a series of tests and available results from past research. Finite element models of gypsum plasterboard panels were then developed to simulate their thermal behaviour under standard fire conditions. The accuracy of the proposed thermal properties and the finite element models was validated by comparing the numerical results with available fire test results of plasterboard panels. This paper presents the details of the finite element models of plasterboard panels, the thermal analysis results from finite element analyses under standard fire conditions and their comparisons with experimental results

Polycaprolactone-based scaffold plus recombinant human bone morphogenic protein rhBMP-2) in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. The resulting spinal deformity consists of coronal curvature, hypokyphosis of the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral (IV) discs have been surgically cleared and the disc spaces filled with graft material. Recently a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone has been developed for bone regeneration at load bearing sites. Combined with rhBMP-2, this has been shown to be successful in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft alone. The study aimed to establish a large animal thoracic spine interbody fusion model, develop spine biodegradable scaffolds (PCL) in combination with biologics (rhBMP-2) and to establish a platform for research into spine tissue engineering constructs. Preliminary results demonstrate higher grades of radiologically evident bony fusion across all levels when comparing fusion scores between the 3 and 6 month postop groups at the PCL CaP coated scaffold level, which is observed to be a similar grade to autograft, while no fusion is seen at the scaffold only level. Results to date suggest that the combination of rhBMP-2 and scaffold engineering actively promotes bone formation, laying the basis of a viable tissue engineered constructs.

Biomechanical performance of polycaprolactone (PCL)-based scaffold with rhBMP-2 in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. Resulting spine deformities include progressive coronal curvature, hypokyphosis, or frank lordosis in the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral discs have been surgically cleared and the disc spaces filled with graft material. Problems with bone graft harvest site morbidity as well as limited bone availability have led to the search for bone graft substitutes. Recently, a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone (PCL) has been developed for bone regeneration at load bearing sites. Combined with recombinant human bone morphogenic protein–2 (rhBMP-2), this has been shown to be successful in acting as a bone graft substitute in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft. This in vivo sheep study intends to evaluate the suitability of a custom designed medical grade PCL scaffold in combination with rhBMP-2 as a bone graft substitute in the setting of mini–thoracotomy surgery as a platform for ongoing research to benefit patients with adolescent idiopathic scoliosis.

Shear strengths of lipped channel beams with stiffened web openings using numerical studies

This paper presents the details of numerical studies on the shear behaviour and strength of lipped channel beams (LCBs) with stiffened web openings. Over the last couple of decades, cold-formed steel beams have been used extensively in residential, industrial and commercial buildings as primary load bearing structural components. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. Our research has shown that shear strengths of LCBs were reduced by up to 70% due to the inclusion of web openings. Hence there is a need to improve the shear strengths of LCBs with web openings. A cost effective way to improve the detrimental effects of a large web opening is to attach appropriate stiffeners around the web openings in order to restore the original shear strength and stiffness of LCBs. Hence numerical studies were undertaken to investigate the shear strengths of LCBs with stiffened web openings. In this research, finite element models of LCBs with stiffened web openings in shear were developed to simulate the shear behaviour and strength of LCBs. Various stiffening methods using plate and LCB stud stiffeners attached to LCBs using screw-fastening were attempted. The developed models were then validated by comparing their results with experimental results and used in parametric studies. Both finite element analysis and experimental results showed that the stiffening arrangements recommended by past re-search for cold-formed steel channel beams are not adequate to restore the shear strengths of LCBs with web openings. Therefore new stiffener arrangements were proposed for LCBs with web openings based on experimental and finite element analysis results. This paper presents the details of finite element models and analyses used in this research and the results including the recommended stiffener arrangements.

Design of LSF wall studs under fire conditions

Cold-formed steel lipped channels are commonly used in LSF wall construction as load bearing studs with plasterboards on both sides. Under fire conditions, cold-formed thin-walled steel sections heat up quickly resulting in fast reduction in their strength and stiffness. Usually the LSF wall panels are subjected to fire from one side which will cause thermal bowing, neutral axis shift and magnification effects due to the development of non-uniform temperature distributions across the stud. This will induce an additional bending moment in the stud and hence the studs in LSF wall panels should be designed as a beam column considering both the applied axial compression load and the additional bending moment. Traditionally the fire resistance rating of these wall panels is based on approximate prescriptive methods. Very often they are limited to standard wall configurations used by the industry. Therefore a detailed research study is needed to develop fire design rules to predict the failure load and hence the failure time of LSF wall panels subject to non-uniform temperature distributions. This paper presents the details of an investigation to develop suitable fire design rules for LSF wall studs under non-uniform elevated temperature distributions. Applications of the previously developed fire design rules based on AISI design manual and Eurocode 3 Parts 1.2 and 1.3 to LSF wall studs were investigated in detail and new simplified fire design rules based on AS/NZS 4600 and Eurocode 3 Part 1.3 were proposed in the current study with suitable allowances for the interaction effects of compression and bending actions. The accuracy of the proposed fire design rules was verified by using the results from full scale fire tests and extensive numerical studies.

An exploratory study of the potential of resurfacing articular cartilage with synthetic phospholipids

This thesis is aimed at further understanding the uppermost lipid-filled membranous layer (i.e. surface amorphous layer (SAL)) of articular cartilage and to develop a scientific framework for re-introducing lipids onto the surface of lipid-depleted articular cartilage (i.e. "resurfacing"). The outcome will potentially contribute to knowledge that will facilitate the repair of the articular surface of cartilage where degradation is limited to the loss of the lipids of the SAL only. The surface amorphous layer is of utmost importance to the effective load-spreading, lubrication, and semipermeability (which controls its fluid management, nutrient transport and waste removal) of articular cartilage in the mammalian joints. However, because this uppermost layer of cartilage is often in contact during physiological function, it is prone to wear and tear, and thus, is the site for damage initiation that can lead to the early stages of joint condition like osteoarthritis, and related conditions that cause pain and discomfort leading to low quality of life in patients. It is therefore imperative to conduct a study which offers insight into remedying this problem. It is hypothesized that restoration (resurfacing) of the surface amorphous layer can be achieved by re-introducing synthetic surface-active phospholipids (SAPL) into the joint space. This hypothesis was tested in this thesis by exposing cartilage samples whose surface lipids had been depleted to individual and mixtures of synthetic saturated and unsaturated phospholipids. The surfaces of normal, delipidized, and relipidized samples of cartilage were characterized for their structural integrity and functionality using atomic force microscope (AFM), confocal microscope (COFM), Raman spectroscopy, magnetic resonance imaging (MRI) with image processing in the MATLAB® environment and mechanical loading experiments. The results from AFM imaging, confocal microscopy, and Raman spectroscopy revealed a successful deposition of new surface layer on delipidized cartilage when incubated in synthetic phospholipids. The relipidization resulted in a significant improvement in the surface nanostructure of the artificially degraded cartilage, with the complete SAPL mixture providing better outcomes in comparison to those created with the single SAPL components (palmitoyl-oleoyl-phosphatidylcholine, POPC and dipalmitoyl-phosphatidylcholine, DPPC). MRI analysis revealed that the surface created with the complete mixture of synthetic lipids was capable of providing semipermeability to the surface layer of the treated cartilage samples relative to the normal intact surface. Furthermore, deformation energy analysis revealed that the treated samples were capable of delivering the elastic properties required for load bearing and recovery of the tissue relative to the normal intact samples, with this capability closer between the normal and the samples incubated in the complete lipid mixture. In conclusion, this thesis has established that it is possible to deposit/create a potentially viable layer on the surface of cartilage following degradation/lipid loss through incubation in synthetic lipid solutions. However, further studies will be required to advance the ideas developed in this thesis, for the development of synthetic lipid-based injections/drugs for treatment of osteoarthritis and other related joint conditions.

Diffusion-sensitive magnetic resonance spectroscopy and imaging in biomedical sciences

We present a mini-review of the development and contemporary applications of diffusion-sensitive nuclear magnetic resonance (NMR) techniques in biomedical sciences. Molecular diffusion is a fundamental physical phenomenon present in all biological systems. Due to the connection between experimentally measured diffusion metrics and the microscopic environment sensed by the diffusing molecules, diffusion measurements can be used for characterisation of molecular size, molecular binding and association, and the morphology of biological tissues. The emergence of magnetic resonance was instrumental to the development of biomedical applications of diffusion. We discuss the fundamental physical principles of diffusion NMR spectroscopy and diffusion MR imaging. The emphasis is placed on conceptual understanding, historical evolution and practical applications rather than complex technical details. Mathematical description of diffusion is presented to the extent that it is required for the basic understanding of the concepts. We present a wide range of spectroscopic and imaging applications of diffusion magnetic resonance, including colloidal drug delivery vehicles; protein association; characterisation of cell morphology; neural fibre tractography; cardiac imaging; and the imaging of load-bearing connective tissues. This paper is intended as an accessible introduction into the exciting and growing field of diffusion magnetic resonance.

Damage detection in cable structures using vibration characteristics

Cable structures find many applications such as in power transmission, in anchors and especially in bridges. They serve as major load bearing elements in suspension bridges, which are capable of spanning long distances. All bridges, including suspension bridges, are designed to have long service lives. However, during this long life, they become vulnerable to damage due to changes in loadings, deterioration with age and random action such as impacts. The main cables are more vulnerable to corrosion and fatigue, compared to the other bridge components, and consequently reduces the serviceability and ultimate capacity of the bridge. Detecting and locating such damage at the earliest stage is challenging in the current structural health monitoring (SHM) systems of long span suspension bridges. Damage or deterioration of a structure alters its stiffness, mass and damping properties which in turn modify its vibration characteristics. This phenomenon can therefore be used to detect damage in a structure. The modal flexibility, which depends on the vibration characteristics of a structure, has been identified as a successful damage indicator in beam and plate elements, trusses and simple structures in reinforced concrete and steel. Successful application of the modal flexibility phenomenon to detect and locate the damage in suspension bridge main cables has received limited attention in recent research work. This paper, therefore examines the potential of the modal flexibility based Damage Index (DI) for detecting and locating damage in the main cable of a suspension bridge under four different damage scenarios. Towards this end, a numerical model of a suspension bridge cable was developed to extract the modal parameters at both damaged and undamaged states. Damage scenarios considered in this study with varied location and severity were simulated by changing stiffness at particular locations of the cable model. Results confirm that the DI has the potential to successfully detect and locate damage in suspension bridge main cables. This simple method can therefore enable bridge engineers and managers to detect and locate damage in suspension bridges at an early stage, minimize expensive retrofitting and prevent bridge collapse.

Vulnerability and damage analysis of reinforced concrete framed buildings subjected to near field blast events

Terrorists usually target high occupancy iconic and public buildings using vehicle borne incendiary devices in order to claim a maximum number of lives and cause extensive damage to public property. While initial casualties are due to direct shock by the explosion, collapse of structural elements may extensively increase the total figure. Most of these buildings have been or are built without consideration of their vulnerability to such events. Therefore, the vulnerability and residual capacity assessment of buildings to deliberately exploded bombs is important to provide mitigation strategies to protect the buildings' occupants and the property. Explosive loads and their effects on a building have therefore attracted significant attention in the recent past. Comprehensive and economical design strategies must be developed for future construction. This research investigates the response and damage of reinforced concrete (RC) framed buildings together with their load bearing key structural components to a near field blast event. Finite element method (FEM) based analysis was used to investigate the structural framing system and components for global stability, followed by a rigorous analysis of key structural components for damage evaluation using the codes SAP2000 and LS DYNA respectively. The research involved four important areas in structural engineering. They are blast load determination, numerical modelling with FEM techniques, material performance under high strain rate and non-linear dynamic structural analysis. The response and damage of a RC framed building for different blast load scenarios were investigated. The blast influence region for a two dimensional RC frame was investigated for different load conditions and identified the critical region for each loading case. Two types of design methods are recommended for RC columns to provide superior residual capacities. They are RC columns detailing with multi-layer steel reinforcement cages and a composite columns including a central structural steel core. These are to provide post blast gravity load resisting capacity compared to typical RC column against a catastrophic collapse. Overall, this research broadens the current knowledge of blast and residual capacity analysis of RC framed structures and recommends methods to evaluate and mitigate blast impact on key elements of multi-storey buildings.