Pernilla Eliasson

Linköping University | LiU · Department of Clinical and Experimental Medicine (IKE)

Heterotopic mineralization entails pathological mineral formation inside soft tissues. In human tendons mineralization is often associated with tendinopathies, tendon weakness and pain. In Achilles tendons, mineralization is considered to occur through heterotopic ossification (HO) primarily in response to tendon pathologies. However, refined detai...

The specific viscoelastic mechanical properties of Achilles tendons are highly dependent on the structural characteristics of collagen at and between all hierarchical levels. Research has been conducted on the deformation mechanisms of positional tendons and single fibrils, but knowledge about the coupling between the whole tendon and nanoscale def...

Background Early tensile loading improves material properties of healing Achilles tendon ruptures in animal models and in surgically treated human ruptures. However, the effect of such rehabilitation in patients who are nonsurgically treated remains unknown. Hypothesis In nonsurgically treated Achilles tendon ruptures, early tensile loading would...

Background: Corticosteroid treatments such as dexamethasone are commonly used to treat tendinopathy but with mixed outcomes. Although this treatment can cause tendon rupture, it can also stimulate the tendon to heal. However, the mechanisms behind corticosteroid treatment during tendon healing are yet to be understood. Purpose: To comprehend whe...

Ruptures to tendons are common and costly, and no clinical consensus exists on the appropriate treatment and rehabilitation regimen to promote their healing as well as full recovery of functionality. Although mechanobiology is known to play an important role in tendon regeneration, the understanding of how mechano-regulated processes affect tendon...

Achilles tendons are mechanosensitive, and their complex hierarchical structure is in part the result of the mechanical stimulation conveyed by the muscles. To fully understand how their microstructure responds to mechanical loading a non-invasive approach for 3D high resolution imaging suitable for soft tissue is required. Here we propose a protoc...

Tendon tissue storage and preconditioning are often used in biomechanical experiments and whether this generates alterations in tissue properties is essential to know. The effect of storage and preconditioning on dense connective tissues, like tendons, is fairly understood. However, healing tendons are unlike and contain a loose connective tissue....

This work explores the modelling of soft tissues, particularly the Achilles tendon, using the absolute nodal coordinate formulation (ANCF). The anisotropic Gasser-Ogden-Holzapfel (GOH) potential energy function provided the necessary anisotropic elastic feature descriptions. A generalized one-dimensional Maxwell model described the viscoelastic eff...

Mechanical loading affects tendon healing and recovery. However, our understanding about how physical loading affects recovery of viscoelastic functions, collagen production and tissue organisation is limited. The objective of this study was to investigate how different magnitudes of loading affects biomechanical and collagen properties of healing...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Elastic fibers containing elastin play an important role in tendon functionality, but the knowledge on presence and function of elastin during tendon healing is limited. The aim of this study was to investigate elastin content and distribution in intact and healing Achilles tendons and to understand how elastin influence the viscoelastic properties...

Mechanical loading affects tendon healing and recovery. However, our understanding about how physical loading affects recovery of viscoelastic functions, collagen production and tissue organisation is limited. The objective of this study was to investigate how different magnitudes of loading affects biomechanical and collagen properties of healing...

Elastic fibers containing elastin play an important role in tendon functionality, but the knowledge on presence and function of elastin during tendon healing is limited. The aim of this study was to investigate elastin content and distribution in intact and healing Achilles tendons and to understand how elastin influence the viscoelastic properties...

Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast...

We have previously shown that changes in the microbiome influence how the healing ten- don responds to different treatments. The aim of this study was to investigate if changes in the microbiome influence the response to mechanical loading during tendon healing. 90 Sprague-Dawley rats were used. Specific Opportunist and Pathogen Free (SOPF) rats we...

Background: Tendon loading might play a role in the development of heterotopic ossification after Achilles tendon ruptures. Early heavy loading on a healing tendon in animals has been shown to prolong the proinflammatory response, and inflammatory cells are thought to drive heterotopic ossification formation. Taken together, this suggests that ear...

Recent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to experimentally understand the pathogenesis of statin i...

Tendon cells exist in a dense extracellular matrix (ECM) and mechanical loading is important for the strength development of this matrix. We therefore use a three‐dimensional (3D) culture system for tendon formation in vitro. The objectives of this study were to elucidate the temporal expression of tendon related genes during the formation of artif...

As cytotoxic (CD8⁺) T cells seem to impair shaft fracture healing, we hypothesized that depletion of CD8⁺ cells would instead improve healing of cancellous bone. Additionally, we also tested if CD8‐depletion would influence the healing of ruptured Achilles tendons. Rats received a single injection of either anti‐CD8 antibodies or saline and put thr...

Methods Aim To investigate the effect of the microbiome on the response to mechanical loading. Conclusion The positive effect of loading on tendon healing is influenced by the microbiome and thereby the immune system. Future animal experiments aiming for clinical relevance should probably take the microbiome into account.

Tendon healing is influenced by immune system cells and a change in the microbiome affects the response to different immune modulating treatments 1,2. Mechanical loading profoundly influences tendon healing and possibly through an altered immune cells composition and immunological response 3,4. We hypothesize that a change in the microbiome can aff...

Background: The immune system reflects the microbiome (microbiota). Modulation of the immune system during early tendon remodeling by dexamethasone treatment can improve rat Achilles tendon healing. The authors tested whether changes in the microbiota could influence the effect of dexamethasone treatment. Hypothesis: A change in microbiome would...

Background Mechanical loading stimulates Achilles tendon healing. However, various degrees of loading appear to have different effects on the mechanical properties of the healing tendon, and strong loading might create microdamage in the tissue. This suggests that different mechanisms might be activated depending on the magnitude of loading. The ai...

Data from Quantitative real-time PCR. CT values for each gene and each rat. (XLSX)

Data from mechanical evaluation. Data from each rat for callus width and depth, gap distance, transverse area, peak force, peak stress, stiffness, elastic modulus, and energy uptake. (XLSX)

Data from detection of microdamage. Detection of leakage of BSA-FITC in the tissue and in blood. TW means tissue weight; FBP means Fluorescence in the Blood Plasma (counts/s); FT means Fluorescence in the Tendon (counts/s). (XLSX)

Background: Treatment strategies for Achilles tendon rupture vary considerably, and clinical outcome may depend on the magnitude of tendon elongation after surgical repair. The aim of this project was to examine whether tendon elongation, mechanical properties, and functional outcomes during rehabilitation of surgically repaired acute Achilles ten...

The role of inflammation and the mechanism of tendon healing after rupture has historically been a matter of controversy. The purpose of the present study is to investigate the role of mast cells and their relation to the NMDA receptor-1 (a glutamate receptor) during healing after Achilles tendon rupture. Eight female Sprague Dawley rats had their...

Mechanical loading stimulates tendon healing both when applied in the inflammatory phase and in the early remodeling phase of the process, although not necessarily via the same mechanisms. We investigated the gene response to mechanical loading in these two phases of tendon healing. The right Achilles tendon in rats was transected and the hind limb...

Treatment with lipid-lowering drugs, statins, is common all over the world. Lately, the occurrence of spontaneous tendon ruptures or tendinosis have suggested a negative influence of statins upon tendon tissue. But how statins might influence tendons is not clear. In the present study, we investigated the effect of statin treatment on mechanical st...

Gene expression analysis: Effect of treatment on collagen, MMPs and TIMP-1. The gene expression after 1 or 7 days of statin treatment presented as the absolute values in arbitrary units (A.U.), which is a ratio between the mRNA and the housekeeping mRNA (RPLP0). Data is presented on a logarithmic y scale and the line represents the mean value. Indi...

Gene expression analysis: Effect of time. Normalized gene expression after 7 days of culture. The DMSO-controls from day 7 were all normalized to the corresponding DMSO-control at day 1 to illustrate the time effect. There was a significantly increased expression of tenomodulin from day 1 to day 7 and a reduced expression of TIMP-1 during this same...

Gene expression analysis: Effect of treatment on GAPDH, heat shock proteins and tendon related genes. The gene expression after 1 or 7 days of statin treatment presented as the absolute values in arbitrary units (A.U.), which is a ratio between the mRNA and the housekeeping mRNA (RPLP0). Data is presented on a logarithmic y scale and the line repre...

Advanced Glycation Endproducts (AGEs) accumulate in long?lived tissue proteins like collagen in bone and tendon causing modification of the biomechanical properties. This has been hypothesized to raise the risk of orthopedic injury such as bone fractures and tendon ruptures. We evaluated the relationship between AGE content in the diet and accumula...

The healing process of ruptured tendons is problematic due to scar tissue formation and deteriorated material properties, and in some cases, it may take nearly a year to complete. Mechanical loading has been shown to positively influence tendon healing; however, the mechanisms remain unclear. Computational mechanobiology methods employed extensivel...

Purpose: Following Achilles tendon rupture, running is often allowed after 6 months. However, tendon healing is slow and the metabolic status of the tendon at this point is unknown. The purpose of this study was to investigate tendon metabolism (glucose uptake) and vascularization at 3, 6 and 12 months after Achilles tendon rupture as measured usi...

Background: Computational models of Achilles tendons can help understanding how healthy tendons are affected by repetitive loading and how the different tissue constituents contribute to the tendon's biomechanical response. However, available models of Achilles tendon are limited in their description of the hierarchical multi-structural compositio...

Lysyl oxidases (LOXs) are a family of copper- dependent oxido-deaminases that can modify the side-chain of lysyl residues in collagen and elastin, thereby leading to the spontaneous formation of non-reducible aldehyde-derived inter-polypeptide chain cross-links. The consequences of LOX inhibition in producing lathyrism are well documented but the c...

we investigated how ruptured Achilles tendons are loaded in a brace. There is an ongoing discussion whether patients should be recommended to bear weight on the injured limb. However, little is known about the effects of bracing on tensional loading of the healing Achilles tendon: it is uncertain if load-bearing actually stresses the Achilles tendo...

(1) Objective Isolated human tendon cells form 3D tendon constructs that demonstrate collagen fibrillogenesis and feature structural similarities to tendon when cultured under tensile load. The exact role of circulating growth factors for collagen formation in tendon is sparsely examined. We investigated the influence of insulin-like growth factor...

Achilles tendon rupture is a frequent injury with an increasing incidence. Until now, there is no consensus regarding optimal treatment. The aim of this review was to illuminate and summarize randomized controlled trials comparing surgical and non-surgical treatment of Achilles tendon ruptures during the last 10 years. Seven articles were found and...

Mechanical loading increases the strength of healing tendons, but also induces small localized bleedings. Therefore, it is unclear if increased strength after loading is a response to mechanotransduction or microtrauma. We have previously found only 5 genes to be up-regulated 15 minutes after a single loading episode, of them 4 transcription factor...

Mechanical loading can influence tendon collagen homeostasis in animal models, while the dynamics of the human adult tendon core tissue is more debatable. Currently available data indicate that human tendon adaptation to loading may happen primarily in the outer tendon region. A role of inflammation in this peri-tendinous adaptation is supported by...

Loading can stimulate tendon healing. In healing rat Achilles tendons, we have found more than 150 genes up-or down-regulated 3 hours after one loading episode. We hypothesized that these changes were preceded by a smaller number of regulatory genes and therefore now performed a microarray 15 minutes after a short loading episode, to capture the pr...

Background and purpose Extracellular matrix remodeling is altered in rotator cuff tears, partly due to altered expression of matrix metalloproteinases (MMPs) and their inhibitors. It is unclear whether this altered expression can be traced as changes in plasma protein levels. We measured the plasma levels of MMPs and their tissue inhibitors (TIMPs)...

Treatment of tendon injuries often involves immobilization. However, immobilization might not prevent mild involuntary isometric muscle contraction. The effect of weak forces on tendon healing is therefore of clinical interest. Studies of tendon healing with various methods for load reduction in rat Achilles tendon models show a consistent reductio...

The pathogenesis of trigger finger has generally been ascribed to primary changes in the first annular ligament. In contrast, we recently found histological changes in the tendons, similar to the findings in Achilles tendinosis or tendinopathy. We therefore hypothesized that trigger finger tendons would show differences in gene expression in compar...

Should blockade of TNF-α be avoided after orthopedic surgery? Healing of injuries in soft tissues and bone starts with a brief inflammatory phase. Modulation of inflammatory signaling might therefore interfere with healing. For example, Cox inhibitors impair healing in animal models of tendon, ligament, and bone injury, as well as in fracture patie...

Growth Hormone stimulates bone growth and fracture repair. It acts mainly by increasing the systemic levels of IGF-1. Local treatment with IGF-1 appears to stimulate tendon healing. We therefore hypothesized that systemic treatment with Growth Hormone would also stimulate tendon healing. Rat Achilles tendons were transected and left to heal. 4 grou...

The pathogenesis of trigger finger has generally been ascribed to primary changes in the pulley. Histological examination of the affected tendons has rarely been done. We studied biopsies from tendons of trigger fingers from 29 patients and compared these to biopsies from six intact tendons. We used a modified Movin score, which describes the tendi...

Tendons adapt to changes in mechanical loading, and numerous animal studies show that immobilization of a healing tendon is detrimental to the healing process. The present study addresses whether the effects of a few episodes of mechanical loading are different during different phases of healing. Fifty female rats underwent Achilles tendon transect...

In this study, serum levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) between patients with a history of Achilles tendon rupture and blood donor controls were compared, and their relation to mechanical properties of the tendons during healing were studied. More than 3 years after injury, serum levels of...

Myostatin, a negative regulator of muscle growth, has recently been found to be expressed in tendons. Myostatin-deficient mice have weak and brittle tendons, which suggest that myostatin could be important for tendon maintenance. Follistatin expression in the callus tissue after tendon transection is influenced by loading. We found that follistatin...

Injured tendons require mechanical tension for optimal healing, but it is unclear which genes are upregulated and responsible for this effect. We unloaded one Achilles tendon in rats by Botox injections in the calf muscles. The tendon was then transected and left to heal. We studied mechanical properties of the tendon calluses, as well as mRNA expr...

Intact tendons adapt slowly to changes in mechanical loading, whereas in healing tendons the effect of mechanical loading or its absence is dramatic. The longevity of the response to a single loading episode is, however, unknown. We hypothesized that the tissue has a "memory" of loading episodes and that therefore short loadings are sufficient to e...

Healing of the rat Achilles tendon is sensitive to mechanical loading, and the callus strength is reduced by \( \raise0.5ex\hbox{$\scriptstyle 3$} \kern-0.1em/\kern-0.15em \lower0.25ex\hbox{$\scriptstyle 4$} \) after 14 days, if loading is prevented. Exogenous GDFs stimulate tendon healing. This response is influenced by loading: without loading, c...

Tendons can function as springs and thereby preserve energy during cyclic loading. They might also have damping properties, which, hypothetically, could reduce risk of microinjuries due to fatigue at sites of local stress concentration within the tendon. At mechanical testing, damping will appear as hysteresis. How is damping influenced by training...