Title Affiliations Abstract "Head impact biomechanics for protecting the active ageing population" "Research Group Experimental Neurosurgery and Neuroanatomy" "In Europe, the incidence of fatal and hospitalized traumatic brain injury (TBI) is 262/100.000/year. Lately, a significant increase in the proportion of elderly patients suffering TBI has been observed. This can be explained by changing demographics, better health status allowing them to remain fully active, but also by the presumed mechanical vulnerability of the ageing brain and surrounding tissues.While staying active is rightfully promoted for the elderly, protective headgear customized to the ageing brain for recreational activities associated with a risk for TBI does not exist. Although ‘only’ 18% of the current Belgian population is over 65 year of age, elderly accounted for 38% of nonconcussion TBI hospital admissions and 32% of intensive care admissions in a recent study in Leuven.The IMPAct Group will use its expertise to focus on the increasingly relevant subject of elderly TBI. This will be done by 1) studying injury patterns and risk profiles associated with elderly TBI, 2) experimentally assessing the age-specific material properties and injury thresholds of the relevant tissues (brain, meninges, vasculature) experimentally, 3) incorporating these findings into state-ofthe- art numerical head models, and finally, 4) integrating the obtained age-specific TBI mechanogenesis data into a set of injury thresholds. These can then be used for design of protective gear adapted to the active ageing." "Unravelling the mode of action of low-frequency electromagnetic stimulation in stroke" "Annelies BRONCKAERS" "Cardio & organ systems, Morphology, University of Santiago de Cuba" "Despite the high prevalence and devastating outcome, there are only few treatment options for ischemic stroke. Our project aims to explore low-frequency electromagnetic stimulation (LF-EMS) as a new therapeutic tool for this disease. Recent data of our laboratory indicate that LF-EMS increases survival and neurological outcome in rats and gerbils subjected to severe permanent ischemic stroke. LF-EMS induced migration of endothelial cells (which align the blood vessels) and production of the important messenger molecule nitric oxide (NO) by nitric oxide synthase (NOS) in vitro. Successful repair after stroke consists of also activating other cells such as neurons, microglia and astrocytes. The aim of this project is to investigate the effect of these other cell types. In addition, we will investigate whether LF-EMS has also a beneficial effect in another type of stroke, namely hemorrraghic stroke. Insights obtained in this project will enhance our current knowledge of LF-EMS as a stroke therapy as well as aid in the clinical translation of this therapy." "High-dose locoregional chemotherapy in the lung: towards a less invasive percutaneous technique." "Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)" "Surgical resection of lung metastases is a widely accepted procedure but due to local and distant recurrences reported 5-year survival rates are only 30 to 40%. Reoperations are feasible but often patients become inoperable due to insufficient pulmonary reserve and for this reason new treatment modalities are being investigated. The maximal dose of intravenous chemotherapy is limited due to systemic side-effects, mainly haematological. As is the case with isolated limb and liver perfusion, isolated lung perfusion has the advantage of selectively delivering an agent into the lung while diverting the venous effluent. Phase I and phase II studies have shown that isolated lung perfusion is feasible and may decrease local recurrence rate. However, it remains an invasive technique and less invasive alternative methods are being investigated. Pulmonary artery infusion is such a technique by injecting a cytostatic drug directly in the pulmonary artery without control of the venous effluent. This offers the advantage of high drug exposure in lung parenchyma with some controlled systemic exposure. In this way, isolated lung perfusion is combined with classical intravenous chemotherapy, which may offer an additional advantage to control distant systemic spread. Pulmonary artery infusion is mostly performed with a balloon catheter inflated in the pulmonary artery, so-called blood flow occlusion. The pulmonary circulation is temporarily arrested to allow a better uptake of the injected drug in the lung parenchyma. This represents a minimally invasive, endovascular technique, which can be repeated several times and which can also be applied in patients who cannot tolerate one-lung ventilation or initially, have inoperable lung metastases or even primary lung cancer. In the present research proposal, a minimally invasive and percutaneous method and device of use will be developed and tested in vitro to occlude and infuse/perfuse a lung locoregionally in large animals and patients. Devices and method are tested in vitro. Results are discussed in a design review whereby the parties concerned will jointly decide whether or not the objectives have been met which will conclude the investigation under this application. Regarding subsequent investigations, pulmonary infusion will be evaluated in a pig model of blood flow occlusion with injection of gemcitabine as this drug was found to be most promising in the experimental rodent setting. Pharmacokinetics will be determined specifically looking at lung and systemic concentrations. Afterwards, a phase I trial will be performed in patients with inoperable lung metastases or primary lung cancer. When the dose-limiting toxicity and maximum tolerated dose have been determined, a phase II trial may be designed similar to what as has been performed for isolated lung perfusion. By combining both worlds of high locoregional and distant exposure of chemotherapeutic drugs, we hope to improve the overall and disease-free survival rate of our patients with lung metastases or primary lung cancer." "Low-frequency electromagnetic stimulation: exploring the (sub) cellular mechanisms in ischemic stroke" "Annelies BRONCKAERS" "Cardio & organ systems, Morphology" "Despite the high prevalence and devastating outcome, there are only few treatment options for ischemic stroke. Our project aims to explore magnetic stimulation (MS) as a new therapeutic tool. Preliminary data of our laboratory indicates that MS increases survival and neurological outcome in rats and gerbils subjected to severe permanent stroke. MS induced migration of endothelial cells (which align the blood vessels) and production of the important messenger molecule nitric oxide by nitric oxide synthase (NOS) in vitro. Successful repair after stroke consists of activating the endothelial cells and simultaneously protecting neurons from ischemic damage. Our preliminary data point to NO as a key regulator of magnetic stimulation-induced protection. Elucidating the link between magnetic stimulation, NO and brain repair after ischemic stroke is the goal of this project. We study how the produced NO promotes blood flow recovery by vessel dilatation (collateralization) in vivo. In addition, we investigate the subcellular mechanisms by which magnetic stimulation activates NOS in endothelial cells and how magnetic stimulation inhibits neuronal cell death. Insights obtained in this project will enhance our current knowledge of magnetic stimulation as well as of endogenous cellular and subcellular mechanisms after stroke." "Evaluation and simulation of the contact pressure in biological intercalary reconstruction surgery after bone sarcoma resection." "Gunther Steenackers" "Industrial Vision Lab (InViLab)" "Bone cancer affects children and young adults and requires wide removal of bone, leaving large defects. In order to save the limb and to restore its function in a lasting way, dead bone from bone banks or sterilised removed bone (graft) is used to fill the defect and is fixed by plates and screws. Still, in some patients a gap between the dead graft and the remaining living bone is seen, causing a delayed healing which leads to prolonged non-weight bearing periods (>1 year) and reoperations. We aim to reduce the healing time by introducing a predefined compression force to a graft, comparable to methods used in fracture fixation and megaprosthesis ingrowth. However, no literature is available evaluating the compression force and its effect on graft healing. Moreover, as bone cancer is extremely rare, this small patient group is often ignored for research funding to improve the current knowledge. We need to reproduce this compression force in a reliable way in different patients and different bone parts. Therefore we need to develop a standardised surgical procedure and determine the relation between the compression force and the surgical variables, eg screw positioning. Data from in vitro cyclic loading experiments and the patient's characteristics will be used for virtual simulation of compression force during level walking. These data will be essential for the future introduction and development of innovative techniques such as patient-specific instruments and implants." "Predicting outcome after total knee replacement surgery in patients with knee osteoarthritis: a prospective study on the role of altered central pain processing in addition to structural and functional impairments related to knee osteoarthritis." "Mira Meeus" "Movement Antwerp (MOVANT)" "Even though a Total Knee Replacement (TKR) is an effective surgical treatment for end-stage knee osteoarthritis (KOA) and the majority of patients report substantial pain relief and functional improvement following this surgical procedure, literature shows that 20-40% of patients are dissatisfied with the postsurgical outcome. Similar to other chronic pain conditions, there is growing body of research suggesting that in a subgroup of patients with KOA the clinical picture is dominated by sensitization of central nervous system pain pathways (i.e. central sensitization) rather than by structural dysfunctions causing nociceptive pain. Briefly, this means that the pain is to a considerable degree due to hypersensitivity of the central nervous system, rather than being just caused by structural joint damage. Therefore, it is not surprising that surgical interventions such as TKRs do not guarantee pain reduction and functional recovery, as the pain goes beyond the joint. Given the high costs related to TKR surgery and the substantial number of patients who do not meet the level of improvement after surgery, the decision to implant a TKR should be very well-considered. It is crucial to improve our understanding of the mechanisms contributing to persisting pain and disability following TKR and it emphasizes the need for further research on the role of altered central pain processing in patients with end stage KOA awaiting TKR surgery.This research proposal has two main objectives:1) to unravel to which extent central pain processing and structural and functional impairments contribute to the clinical expression of KOA (pain, symptoms, physical performance and quality of life) in patients with end-stage KOA before (at baseline) and 6 months after primary TKR surgery. 2) to unravel which factors are predictive for an unsatisfactory outcome (in terms of pain, symptoms, physical performance and quality of life) 6 months and 1 year after a primary TKR. In order to reach these objectives, a longitudinal prospective study will be performed, with specific data collection presurgical (T0) and 6 months (T1) and 1 year (T2) postsurgical.This study allows identification of prognostic factors for unsatisfactory outcome in KOA patients after a primary TKR. Previous longitudinal studies investigating predictors of poor outcome after TKR, mainly focused on structural and functional factors related to the knee joint, while central pain processing was left unnoticed. Other studies mainly focused on psychological factors as potential predictors of poor outcome. The strength of the recent proposal is that we will examine all putative prognostic factors on the basis of the biopsychosocial model. Besides several psychological factors (cognitive emotional modulation), we assess biomechanical factors (i.e. structural impairments, such as radiographic severity of OA, and functional impairments such as muscle weakness and proprioceptive deficits) and examine the role of altered central pain processing measured in four ways (Pressure Pain Thresholds, Conditioned Pain Modulation, tactile acuity, Central Sensitization Inventory questionnaire). In this study, it is hypothesized that in patients with altered central pain processing an unsatisfactory effect of TKR surgery on KOA pain, symptoms, physical performance and quality of life can be expected, as there is no clear relation between peripheral input and perceived pain. It is possible that in this subgroup interventions aiming to desensitize the central nervous system might be more beneficial.In future interventional research, it can be clarified whether new interventions, such as cognitive-behavioral therapy or therapeutic pain neuroscience education, whether or not in combination with surgery, are useful. These new interventions target different aspects such as the central nervous system in contrast to therapeutic modalities that are only directed to structural knee joint pathology." "Scapula Tilter: correction of scapular dyskinesis in patients with subacromial pain syndrome: the ffect of an orthopedic device." "Filip Struyf" "Product development, Movement Antwerp (MOVANT)" "Subacromial pain syndrome is the most common cause of shoulder pain, accounting for 50% of all shoulder pain cases. Scapular dyskinesis has shown to be a key factor associated with many shoulder disorders, such as the subacromial pain syndrome and glenohumeral shoulder instability. Two Master students product development have created (and privately defended) a basic prototype of an orthopaedic device that is aimed at correcting the scapular position. The current project proposal is aimed at bringing this product to the market. First, the prototype will be further developed and adapted with confirmation of its efficacy, i.e. the apparatus can indeed correct scapular position. Second, this improved prototype will be used within a smallscale clinical study to demonstrate that the apparatus can reduce pain in patients with subacromial pain syndrome. At the same time, a trajectory of valorization will be developed to investigate the possibilities of bringing the product to the market." "Mechanical and Structural Alterations after Surgical Treatment of Wrist Osteoarthritis" "Harry van Lenthe" "Development and Regeneration, Kulak Kortrijk Campus, Biomechanics Section" "Wrist osteoarthritis (OA) is one of the most common conditions encountered by hand surgeons. There is no cure to OA. In severe cases, surgical treatment, such as proximal row carpectomy or four corner arthrodesis is performed to reduce pain and to improve mobility; yet, with varying success rates and controversy exists on which procedure is the optimal one. It is hypothesized that patient-specific differences in bone microstructure play a crucial role, such that optimal treatment in one patient may mean overcorrection in others. The aim of this project is to obtain an improved understanding on (i) the alterations in bone microstructure following surgery and on (ii) how these structural alterations are related to alterations in bone loading. Specifically, bone microstructure in patients with wrist OA will be measured using cone-beam CT and the alterations occurring within two years following surgical treatment will be monitored. Reverse engineering and the finite element method will be used to quantify the alterations in mechanical load following treatment. These data are highly needed to improve treatment planning of wrist osteoarthritis." "Predicting outcome after total knee replacement surgery in patients with knee osteoatthritis" "Mira Meeus" "Movement Antwerp (MOVANT)" "Factors predicting poor outcome in knee osteoarthritis patients following total knee jointreplacement (TKR) surgery will be investigated, with focus on the role of pain due toneuroplasticity (i.e. hyperexcitability of the central nervous system).This will increase insight in the success rate and reasons behind the highly varying satisfactionafter TKR and may help in future decision making regarding need for and timing of TKR, aswell as the needs for pre- and postsurgical rehabilitation." "Effect of Human Dental Pulp Stem Cells on the Regeneration of Articular Cartilage: a Study in an Ovine Model of Osteoarthritis." "Cardio & organ systems, Morphology" "Osteoarthritis (OA) is a degenerative and inflammatory condition of synovial joints in which loss of cartilage matrix occurs. Despite advances in technologies, durable restoration of damaged articular cartilage is still an unachieved goal. This is mainly caused by a reduced vascularity, limited cell populations and dense extracellular matrix. Data suggest that chondrocyte implantation could be efficient for treating chondral lesions. However, the use of adult autologous chondrocytes is associated with several drawbacks. To overcome these problems, the use of advanced biological tissue engineering techniques utilizing stem cells forms an area of large interest in order to make cartilage regeneration possible. Bone marrow-derived mesenchymal stem cells (MSCs) have been frequently used to treat chondral lesions in preclinical settings. However, because the isolation of BMMSCs is invasive and painful, we would like to use human dental pulp stem cells (hDPSCs). Furthermore, hDPSCs have been reported to be immune-modulatory. Therefore, we hypothesize that hDPSCs improve the functional outcome in OA via immunomodulatory effects and stimulation of cartilage regeneration. We will focus on longitudinal monitoring of functional improvement in an ovine model of OA, combined with assessing the in vivo biodistribution of the stem cells within the joint cavity. Furthermore, the effects of this stem cell therapy on the immunologic response will be evaluated."