Magnus B. Lilledahl's research while affiliated with Norwegian University of Science and Technology and other places

Publications (45)

Article
Full-text available
Objective Despite new strategies in tissue engineering, cartilage repair remains a major challenge. Our aim is to treat patients with focal lesions of articular cartilage with autologous hyaline cartilage implants using a scaffold-free approach. In this article, we describe experiments to optimize production of scaffold-free cartilage discs. Desig...
Article
Full-text available
While a detailed knowledge of the hierarchical structure and morphology of the extracellular matrix is considered crucial for understanding the physiological and mechanical properties of bone and cartilage, the orientation of collagen fibres and carbonated hydroxyapatite (HA) crystallites remains a debated topic. Conventional microscopy techniques...
Conference Paper
Unstained microscopy of growth cartilage microstructure is crucial for understanding bone formation and related diseases. Here, we compare imaging modalities with unconventional contrast mechanisms applied to the epiphyseal bone-cartilage interface and highlight their comparative merits.
Article
Full-text available
Objective We aimed to directly quantify the zone-specific evolution in morphology of collagen fibers and networks in human cartilage during the progression of early osteoarthritis. Collagen fibers exhibit depth-dependent orientations and diameters crucial to their mechanical roles. Cartilage degenerates in osteoarthritis, affecting the morphology o...
Article
Full-text available
The use of videos as learning objects has increased together with an increased variation in the designs of these educational videos. However, to create effective learning objects it is important to have detailed information about how users perceive and interact with the different parts of the multimedia design. In this paper we study, using eye-tra...
Article
According to previous studies, the nonlinear susceptibility tensor ratio χ33/χ31 obtained from polarization resolved second harmonic generation (P‐SHG) under the assumption of cylindrical symmetry can be used to distinguish between fibrillar collagen types. Discriminating between collagen fibrils of type I and II is important in tissue engineering...
Article
Full-text available
Polarization-resolved second harmonic generation (P-SHG) microscopy has evolved as a promising technique to reveal subresolution information about the structure and orientation of ordered biological macromolecules. To extend the adoption of the technique, it should be easily integrated onto commercial laser scanning microscopes. Furthermore, proced...
Article
Osteochondritis dissecans is a joint disease that is observed in several species. The disease can develop as a cause of ischemic chondronecrosis in the epiphyseal growth cartilage. Some lesions of chondronecrosis undergo spontaneous resolution, but it is not possible to predict whether a lesion will resolve or progress and require intervention. Pro...
Article
Full-text available
Osteoarthritis (OA) is a common joint disorder found mostly in elderly people. The role of mechanical behavior in the progression of OA is complex and remains unclear. The stress-relaxation behavior of human articular cartilage in clinically defined osteoarthritic stages may have importance in diagnosis and prognosis of OA. In this study we investi...
Preprint
Full-text available
Osteoarthritis (OA) is a common joint disorder found mostly in elderly people. The role of mechanical behavior in the progression of OA is complex and remains unclear. The stress-relaxation behavior of human articular cartilage in clinically defined osteoarthritic stages may have importance in diagnosis and prognosis of OA. In this study we investi...
Article
Full-text available
Background Articular osteochondrosis is a common cause of leg weakness in pigs and is defined as a focal delay in the endochondral ossification of the epiphysis. The first demonstrated steps in the pathogenesis consist of loss of blood supply and subsequent chondronecrosis in the epiphyseal growth cartilage. Blood vessels in cartilage are located i...
Article
Objective Current systems to evaluate outcomes from tissue-engineered cartilage (TEC) are sub-optimal. The main purpose of our study was to demonstrate the use of second harmonic generation (SHG) microscopy as a novel quantitative approach to assess collagen deposition in laboratory made cartilage constructs. Methods Scaffold-free cartilage constr...
Conference Paper
Multiphoton Microscopy was used for the investigation of osteoarthrtic human articular cartilage. High resolution optical images revealed the hidden features in osteoarthrosis that has not been observed using standard clinical imaging systems.
Chapter
Articular cartilage is located at the bone ends in synovial joints and enables smooth and pain‐free joint motion. Its function is in large part determined by a network of collagen fibrils organized into zones and compartments, but little is known about how this organization is achieved in growing animals [1]. The articular cartilage develops superf...
Article
Purpose: The articular-epiphyseal cartilage complex (AECC) is responsible for the expansion of the bone ends and serves the function of the articular cartilage in juvenile mammals. Bundles of collagen fibrils surrounding cells were in the literature observed more frequently near the articular surface of the AECC. The articular surface, the pericho...
Article
Biomolecular changes in the cartilage matrix during the early stage of osteoarthritis may be detected by Raman spectroscopy. The objective of this investigation was to determine vibrational spectral differences among different grades (grades I, II, and III) of osteoarthritis in human osteoarthritic cartilage, which was classified according to the I...
Article
Full-text available
Understanding of biology is underpinned by the ability to observe structures at various length scales. This is so in a historical context and is also valid today. Evolution of novel insight often emerges from technological advancement. Recent developments in imaging technologies that is relevant for characterization of extracullar microbiological p...
Article
Full-text available
In a synovial joint, the articular cartilage is directly affected during the progression of Osteoarthritis (OA). The characterization of early stage modification in extra-cellular matrix of cartilage is essential for detection as well as understanding the progression of disease. The objective of this study is to demonstrate the potential and capabi...
Article
Full-text available
A great deal of effort has been focused on exploring the underlying molecular mechanism of osteoarthritis (OA) especially at the cellular level. We report a confocal Raman spectroscopic investigation on human osteoarthritic chondrocytes. The objective of this investigation is to identify molecular features and the stage of OA based on the spectral...
Article
The second harmonic generation from collagen is highly sensitive to what extent collagen molecules are ordered into fibrils as the SHG signal is approximately proportional to the square of the fibril thickness. This can be problematic when interpreting SHG images as thick fibers are much brighter than thinner fibers such that quantification of the...
Article
Human atherosclerotic samples collected by carotid endarterectomy were investigated using electronic paramagnetic resonance imaging (EPRI) for visualization of reactive oxygen species, and nonlinear optical microscopy (NLOM) to study structural features. Regions of strong EPRI signal, indicating a higher concentration of reactive oxygen species and...
Article
Due to specific structural organization at the molecular level, several biomolecules (e.g., collagen, myosin etc.) which are strong generators of second harmonic generation (SHG) signals, exhibit unique responses depending on the polarization of the excitation light. By using the polarization second harmonic generation ( p ‐SHG) technique, the valu...
Article
Stromal tissue in the breast plays a key role in cancer invasiveness due to molecular and cellular changes. Collagen is the main component of the stroma. The purposes of this study were to investigate differences in collagen fibre patterns between tumour-induced stromal tissue and normal stroma, and between high-grade and low-grade breast cancer st...
Article
The delivery of nanoparticles to solid tumors is often ineffective due to the lack of specificity towards tumor tissue, limited transportation of the nanoparticles across the vascular wall and poor penetration through the extracellular matrix of the tumor. Ultrasound is a promising tool that can potentially improve several of the transportation ste...
Article
Osteoarthritis is one of the most prevalent joint diseases in the world. Although the cause of osteoarthritis is not exactly clear, the disease results in a degradation of the quality of the articular cartilage including collagen and other extracellular matrix components. We have investigated alterations in the structure of collagen fibers in the c...
Article
Full-text available
A popular approach to make neocartilage in vitro is to immobilize cells with chondrogenic potential in hydrogels. However, functional cartilage cannot be obtained by control of cells only, as function of cartilage is largely dictated by architecture of extracellular matrix (ECM). Therefore, characterization of the cells, coupled with structural and...
Article
A method for measuring three-dimensional (3-D) direction images of collagen fibers in biological tissue is presented. Images of the 3-D directions are derived from the measured transmission Mueller matrix images (MMIs), acquired at different incidence angles, by taking advantage of the form birefringence of the collagen fibers. The MMIs are decompo...
Article
One of the main advantages of nonlinear microscopy is that it provides 3D imaging capability. Second harmonic generation is widely used to image the 3D structure of collagen fibers, and several works have highlighted the modification of the collagen fiber fabric in important diseases. By using an ellipsoidal specific fitting technique on the Fourie...
Article
Cholesterol crystals (ChCs) have been identified as a major factor of plaque vulnerability and as a potential biomarker for atherosclerosis. Yet, due to the technical challenge of selectively detecting cholesterol in its native tissue environment, the physiochemical role of ChCs in atherosclerotic progression remains largely unknown. In this work,...
Article
The collagen meshwork in articular cartilage of chicken knee is characterized using Mueller matrix imaging and multiphoton microscopy. Direction and degree of dispersion of the collagen fibers in the superficial layer are found using a Fourier transform image-analysis technique of the second-harmonic generated image. Mueller matrix images are used...
Article
The 3-D morphology of chicken articular cartilage was quantified using multiphoton microscopy (MPM) for use in continuum-mechanical modeling. To motivate this morphological study we propose aspects of a new, 3-D finite strain constitutive model for articular cartilage focusing on the essential load-bearing morphology: an inhomogeneous, poro-(visco)...
Article
Full-text available
Cartilage from the medial femoral condyle of chicken was sectioned and imaged using second harmonic generation microscopy. Using image analysis techniques based on the Fourier transform we derived quantitative threedimensional data of the fiber direction and dispersion of the collagen fiber network in the superficial layer. These data can be used d...
Chapter
Full-text available
The 3D structure of collagen fibers in chicken cartilage was quantified using multiphoton microscopy. Samples of fresh chicken cartilage were sectioned in three orthogonal planes using a vibratome. The sections were imaged using multiphoton microscopy, specifically imaging the collagen fibers using the second harmonic signal. Employing image analys...
Article
Full-text available
Mechanical models are important in many areas of medicine and physiological research. These are usually based on continuum mechanics using macroscopic mechanical parameters. However, knowledge of the microscopic structure of tissue, that is, the organization of structural proteins, gives useful information for improving such models for a given tiss...
Article
Cardiovascular disease is the primary cause of death in the United States; the majority of these deaths are caused by the rupture of vulnerable plaques. An important feature of vulnerable plaques is the thickness of the fibrous cap that covers the necrotic core. A thickness of less than 65 microm has been proposed as a value that renders the plaque...
Article
Intravascular thermography has been proposed as a method for detecting vulnerable plaque. A marker of vulnerability in a plaque is inflammation, which is believed to reduce its mechanical stability. It has been hypothesized that this inflammation leads to a higher metabolic rate and therefore higher heat generation, causing increased temperature in...
Article
Multiphoton microscopy is a techniques that fascilitates three dimensional imaging of intact, unstained tissue. Especially connective tissue has a relatively strong nonlinear optical response and can easily be imaged. Atherosclerosis is a disease where lipids accumulate in the vessel wall and there is a thickening of the intima by growth of a cap o...
Article
Determining the cause of an injury and the force behind the impact may be of crucial importance in a court case. For non-penetrating soft tissue injuries there is a lack of information available in the literature. In this study controlled bruises were inflicted on an anesthetized pig by high speed, low-weight paintball projectiles (diameter 17.1 mm...
Article
When performing intravascular spectroscopy there is always the possibility that there will be a thin layer of blood between the probe and the vessel wall. This will affect measurements espescially below 600 nm where blood absorption is strong (important for fluorescence and Raman measurements) and above 1400 nm where the water absorption is strong....
Article
Heart disease is the primary cause of death in the western world. Many of these deaths are caused by the rupture of vulnerable plaque. Vulnerable plaques are characterized by a large lipid core covered by a thin fibrous cap. One method for detecting these plaques is reflection spectroscopy. Several studies have investigated this method using statis...
Article
An objective method for dating of soft tissue injuries is highly desired in forensic medicine. To achieve this, obtaining a fundamental understanding of extravascular blood behavior is necessary. Porcine blood mixed with fluorescein was inserted subcutaneously on an anaesthetized pig. The fluorescence build-up was measured as a function of time, us...
Article
Many methods for detecting and measuring vulnerable atherosclerotic plaques have been proposed. These include reflection spectroscopy, thermography, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). This paper presents an analysis and a comparison of two of these methods, near-infrared reflection spectroscopy (NIRS) and the...

Citations

... In the current study we have directly compared ACs and BM-MSCs (referred to as MSCs in the following text) as cell candidates for tissue engineering of hyaline cartilage using a scaffold-free strategy to make cartilage discs (Frerker et al., 2021). We observed that ACs made thicker cartilage than MSCs, and propose an explanation for why this occurs. ...
... X-ray diffraction computed tomography (XRD-CT) is a 3D generalization of the conceptually simpler 2D (Mürer et al 2021a), by scanning the sample with a pencil beam and using the scattered or diffracted signal to reconstruct 3D images. Recall that owing to the short wavelength of x-rays of ∼1 Å, comparable to the interatomic spacing in condensed matter, x-ray diffraction gives atomic resolution (Als-Nielsen and McMorrow 2011). ...
... As with most soft tissues, networked collagen fibers at the microscale constitute the major load-bearing structures and they drive the macroscale mechanical properties of the colorectum. The relationship between microscopic collagen structures and macroscopic mechanical properties of soft tissue is reported in many other biological tissues like the skin (Reihsner and Menzel 1998), tendon and cartilage (Ker 1999;Maier et al. 2019;Szarek et al. 2020), and blood vessels (Hariton et al. 2007). Arhan et al. (1976), Dall et al. (1993), Drewes et al. (2001), Petersen et al. (2001), Drewes et al. (2006) Human ...
... While these conditions are defensible from a methodological perspectivebecause they limit confounding variablesit means that caution should be used when applying the resulting findings to contextually different learning situations (Persson et al., 2019). A possible solution to this problem was demonstrated by Merkt et al. (2011), who replicated their experimental study of various levels of video interactivity in a quasi-experimental secondary school setting. ...
... Zhang et al. [13] found that the denaturation temperatures of collagen from sturgeon scale, skin, and cartilage were 29.6, 26.8, and 36.3 • C, respectively. Romijn et al. [14] estimated the χ33/χ31-ratio for type I collagen in tendon and type II collagen in cartilage was 1.33 and 1.36, respectively. This was determined by polarization-resolved second harmonic, which cannot be easily used to differentiate collagen types. ...
... The look-up table was calibrated by measuring the optical polarization state at the back focal plane of the microscope objective lens using a rotating linear polarizer (LPNIRB050-MP2, Thorlabs) and a power meter (S170C, Thorlabs). By coordinating the orientation of these two waveplates, the polarization was maintained at >90% linearly polarized for all measurements [40]. ...
... Even more detailed methods involving photon-excitation fluorescence microscopy techniques are being explored to detect changes in collagen fibrils and cell morphology as predictors of OC lesion progression in pig models (Finnoy et al., 2018). These more recent technologies challenge the "goldstandard" histological techniques and offer exciting methods to improve the understanding of physiological changes involved in the initiation, progression, and potential healing of OC lesions. ...
... Regarding τ, no study has investigated its extent in the same animal model and by applying the same testing method. Although τ can be highly variable and dependent on the site, articulation, model from which AC is retrieved, and testing method [27,38], the values computed are close to those highlighted by a previous study focusing on a different animal model (i.e., porcine), which evaluated the same articulation with the same testing method [29]. ...
... 24 Vessels are believed to fail because they traverse junctions between biomechanically different tissues, such as the junction between growth cartilage and subchondral bone 24,34 and the junction between perichondrium and growth cartilage at sites where ligaments also attach. 10 In epiphyseal growth cartilage, vascular failure results in ischemic necrosis of chondrocytes outside diffusion distance from alternative sources, known as osteochondrosis latens. 6,19,24,34 With time, the ossification front advances to surround the area of necrosis and this causes a delay in endochondral ossification, or osteochondrosis manifesta. ...
... However, important differences exist: it is a coherent process sensitive to the phase-matching conditions where the measured signal arises from constructive/destructive interferences, it is also instantaneous and free from photobleaching as the signal conversion is due to a structural arrangement and does not involve electronic transition 8 . SHG microscopy has been used to image fibrillar collagen in specimens including type II collagen in articular cartilage [9][10][11][12][13][14][15][16] . Furthermore, because of its coherent nature, the detection of the signal in the direction of propagation (forward -F) provides different imaging features compared to the backward (B) direction 17 . ...