FWO grants and other projects

FWO grants and other projects

Acrylate-Terminated Urethane-Based Hydrogel Precursors for Meniscus Tissue Engineering

Özge Begüm Akalin

Promotor: Prof. Peter Dubruel

Acrylate-Terminated Urethane-Based Hydrogel Precursors for Meniscus Tissue Engineering

Meniscus refers to cartilage tissue in the knee and it consists of two semilunar fibrocartilage discs, either lateral or medial. Both provide structural integrity to the knee when it undergoes tension and torsion. The purpose of the meniscus is to act as a stabilizer, shock absorber and space filler between the bones of the knee joint. Adequate and distinctive mechanical properties are necessary for a proper menisci function since it needs to endure constant pressure and endless, intense impacts on the joints. The blood flow of the meniscus is from the periphery to the central and there is no flow in the central region. The presence of blood flow divides the meniscus in three sections. Outer part, middle part and inner part are called as red zone, red-white zone and white zone, respectively. Mostly, tears of the meniscus particularly in the inner part need to be surgically corrected. However, this can cause to osteoarthritic degradation and eventual total knee joint replacement. Providing a meniscal scaffold that compensates biocompatibility and mechanical properties of the native tissue could delay or even prevent the formation of osteoarthritis. A tissue engineered, patient specific 3D-printed meniscus with optimized mechanical and biocompatible properties can be the key solution for meniscal injuries.

The aim of this project is to investigate the application of photopolymerized acrylate-terminated urethane-based polyethylene oxide (PEO) hydrogel precursors (AUP) as porous scaffolds for meniscal tissue engineering. This approach enables to create patient-specific scaffolds with tunable physical properties not only via altering the design but also via altering the backbone molecular weight of the AUPs.

Future research on the AUP scaffolds will be performed including drug release and in vivo testing to enhance the development of a tissue engineered, patient specific 3D-printed meniscus.

Meniscus Tissue Engineering

Development of a superior in vitro model for drug hepatoxicity
screening through 3D printing of crosslinkable biopolymers

Nathan Carpentier

Promotors: Prof. Peter Dubruel, Prof. Sandra Van Vlierberghe

Development of a superior in vitro model for drug hepatoxicity screening through 3D printing of crosslinkable biopolymers

Drug Induced Liver Injury (DILI) is one of the major reasons of drug withdrawal during the different phases of drug development. The process of drug development is very cost- and time intensive and the later a drug is withdrawn from the process or even post market, the higher the economical impact will be. Therefore there is really a need for a more performant model from the liver that can detect the hepatotoxicity of a compound as early as possible in the drug development.

To develop this model, 3D hydrogel scaffolds are established that can support liver cells for a longer period needed for the toxicity tests of drug compounds.

In this project, polysaccharides and proteins are modified towards crosslinkable hydrogel building blocks. These building blocks are printed using various 3D-printing techniques into 3D-hydrogel scaffolds. On this scaffolds, hepatocytes can be seeded in order to develop liver microtissues.

Introducing smart polymers in the field of corneal endothelial tissue engineering: solving a blinding disease

Lobke De Vos

Promotors: Prof. Peter Dubruel, Prof. Sandra Van Vlierberghe

Introducing smart polymers in the field of corneal endothelial tissue engineering: solving a blinding disease

Eye diseases are responsible for a huge economical burden globally, but are also associated with a drastic decrease in quality of life. Some of these diseases are associated to the loss of transparency of the window of the eye, namely the cornea. The cornea is the outermost part of the eye and is composed out of 3 different cell layers. The innermost layer, the corneal endothelium, maintains critical corneal hydration. Upon ageing, disease or trauma, this cell layer can be damaged to such an extent that the cornea swells and loses its transparency, which leads to blindness. Currently, the only treatment consists of full or partial transplantation of a donor cornea. Unfortunately, the supply does not meet the demand by far since only 1 donor is available per 70 patients. To overcome this limitation, the present project aims to develop a synthetic alternative that allows the efficient transplantation of healthy cells towards the site of tissue defect. To this end, biodegradable membranes will be developed using a combination of smart polyesters with shape memory effects, in combination with gelatin derivatives that mimic the cellular environment. These carriers will be seeded with cells, to allow transplantation to the site of tissue defect. Furthermore, the membranes will be analysed in depth both for mechanical properties as in vitro behaviour prior to in vivo animal studies.

Smart polymers to tackle a blinding disease: Corneal endothelial tissue engineering

Jasper Delaey

Promotors: Prof. Peter Dubruel, Prof. Sandra Van Vlierberghe

Introducing smart polymers in the field of corneal endothelial tissue engineering: solving a blinding disease

Eye diseases are responsible for a huge economical burden globally, but are also associated with a drastic decrease in quality of life. Some of these diseases are associated to the loss of transparency of the window of the eye, namely the cornea. The cornea is the outermost part of the eye and is composed out of 3 different cell layers. The innermost layer, the corneal endothelium, maintains critical corneal hydration. Upon ageing, disease or trauma, this cell layer can be damaged to such an extent that the cornea swells and loses its transparency, which leads to blindness. Currently, the only treatment consists of full or partial transplantation of a donor cornea. Unfortunately, the supply does not meet the demand by far since only 1 donor is available per 70 patients. To overcome this limitation, the present project aims to develop a synthetic alternative that allows the efficient transplantation of healthy cells towards the site of tissue defect. To this end, biodegradable membranes will be developed using a combination of smart polyesters with shape memory effects, in combination with gelatin derivatives that mimic the cellular environment. These carriers will be seeded with cells, to allow transplantation to the site of tissue defect. Furthermore, the membranes will be analysed in depth both for mechanical properties as in vitro behaviour prior to in vivo animal studies.

Development of a smart diagnostic antimicrobial hydrogel-based wound dressing

Manon Minsart

Promotors: Prof. Peter Dubruel

Prof. Dr. Ir. A. Mignon (KU Leuven)

Development of a smart diagnostic antimicrobial hydrogel-based wound dressing

Burn wounds lead to an estimated 300 000 deaths per year worldwide. Infection remains the main cause of morbidity and mortality in burn victims. Moreover, diagnosis of wound infection is not always straightforward. One of the critical issues concerning commercial dressings today is their uncontrolled release of bioactive compounds, e.g. antimicrobials. This FWO-SB project focuses on the development of a ‘smart’ burn wound dressing using patented PEG-based acrylate-endcapped urethane-based hydrogel precursors (AUPs), which can be cross-linked with UV-A irradiation and thus form 3D hydrogel networks. Their exceptional solid-state reactivity is particularly of interest for polymer processing through electrospinning. Electrospun fibre mats can provide an excellent environment to promote wound healing by mimicking the native extra-cellular matrix. The ability to incorporate diagnostic as well as antimicrobial compounds in these networks will be especially of interest in this research.

Capturing the biophysical cues of bone to stimulate regeneration in critical bone defects

Laurens Parmentier

Promotors: Prof. Peter Dubruel, Prof. Sandra Van Vlierberghe

Capturing the biophysical cues of bone to stimulate regeneration in critical bone defects

Do you know someone who suffered from a bone defect that had problems to heal after disease, trauma or surgical intervention? The answer is probably yes since bone is the second most commonly tissue transplanted worldwide and is primarily used in critical bone defects in which bone is unable to repair itself through bone remodelling. In order to develop an antimicrobial, patient-specific substitute material that guides bone formation, favours vascularisation and hence stimulates bone repair without commonly reported side-effects associated with conventional grafts such as pain, infections and an enhanced immune response, this project looks at mimicking bone through various biophysical cues such as composition, architecture, mechanical properties and degradation. Moreover, this mimicry will be realised hierarchically on both the macroscopic load-bearing scale of the scaffold fitting the bone defect and the non-load bearing scale of the extracellular matrix substrate providing the appropriate environment for cell adherence, proliferation and differentiation. Dual core-shell 3D bioprinting will be used to fabricate the scaffold consisting of an osteogenic and an angiogenic filament. Characterisation will be performed to target the incorporation of the bone mimicking biophysical cues into the bone substitute material. The proposed material solution offers great potential to tackle current issues towards the development of a bone substitute material that can be used in critically sized bone defects which is of utmost importance given their prevalence, their associated morbidity and their socio-economic implications.

Design, development and validation of a physiologically-relevant model of the vascular wall

Nele Pien

Promotors: Prof. Peter Dubruel, Prof. Sandra Van Vlierberghe

Prof. Dr. D. Mantovani (LBB – ULaval)

Design, development and validation of a physiologically-relevant model of the vascular wall

Diseases of the heart and circulatory system are the leading cause of mortality worldwide, responsible for over 17.9 million deaths annually. In particular, an increasing number of people suffer from coronary artery diseases and the number of coronary interventions is predicted to increase considerably owing to the rapid growth of the elderly population. In this context, tissue engineering (TE) and biomaterial design have gained increasing interest with the final aim to repair, replace or regenerate injured tissues. However, appropriately combining biomaterials (e.g. natural and/or synthetic polymers) with material processing methods and effective techniques for the incorporation of cells into the scaffolds remains one of the major TE challenges. Tissue engineered blood vessels (TEBV) have been proposed as living arterial substitutes but further work is still required to ensure success in clinical translation. Furthermore, there is an urgent and critical need for preclinical testing platforms as reliable alternatives for in vivo assays focusing on intravascular technologies and drug development. Current in vitro artery models require further development because they commonly encounter two interrelated issues: i) the absence of important physiologically-relevant functions, including elasticity, permeability, and vasomotor reactivity, and ii) insufficient mechanical properties, especially in terms of elastic properties.

The present research aims to develop an innovative in vitro model of the vascular wall as a reliable physiologically-relevant alternative to in vivo animal assays. To this end, a reinforced collagen-based model of the vascular wall with human vascular cells (i.e. endothelial cells ECs, smooth muscle cells SMCs and fibroblasts FBs) is designed and developed to establish a biomimetic platform suited for the in vitro assessment of the constructs under physiological conditions. The implementation of collagen, one of the main extracellular matrix (ECM) components of the vascular wall, is of utmost importance for developing a successful in vitro model of the vascular wall. The current project represents a very promising approach for in vitro modeling of vascular tissue because it focuses at the same time on material development, processing and on the stimulation of cells to mature towards functional tissue. These models will allow to investigate physiological as well as pathological processes, the etiology of cardiovascular diseases and to test drugs and devices. Therefore, they will be powerful alternatives for in vivo testing, thereby reducing the number of sacrificed animals.

Development of a biodegradable bone graft for maxillofacial reconstruction

Quinten Thijssen

Promotors:

Prof. Sandra Van Vlierberghe

Maxillofacial Surgeon Robin Willaert (Maxillofacial Surgery Dept. of UZ Leuven)

Development of a biodegradable bone graft for maxillofacial reconstruction

Maxillofacial reconstruction still remains a challenge in the 21st century since the currently available treatments such as autologous bone grafts and titanium implants are very invasive and pose a high risk for infections, often resulting in implant removal.

Therefore, this FWO-SB project focusses on the development of a patient specific and biodegradable implant. A combination of functionalized photo-reactive polymeric building blocks will be investigated as candidate for maxillofacial reconstruction using 3D-printing techniques.

Shape memory polymers based on poly(alkylene terephthalate)s for an improved cardiovascular stent

Lenny Van Daele

Promotors: Prof. Peter Dubruel, Prof. Sandra Van Vlierberghe

Shape memory polymers based on poly(alkylene terephthalate)s for an improved cardiovascular stent

This project involves the use of polymers for cardiovascular applications, more specifically for stents. We aim to develop new polyesters that exhibit shape memory behaviour. Using this polymer technology and surface modifications, we aim to develop a new stent that outperforms the stents that are currently on the market. To this end, an improved endothelialisation and reduced thrombogenicity is within our objectives. Finally, using 3D-printing technology, a personalized stent can be produced which will fit each patient perfectly.

Development of 3D printed core/shell hydrogels towards patient specific breast reconstruction

Lana Van Damme

Promotors: Prof. Sandra Van Vlierberghe

Prof. Phillip Blondeel

Development of 3D printed core/shell hydrogels towards patient specific breast reconstruction

Nowadays, breast implants and micro-surgical free tissue transfer are the most popular procedures to repair soft tissue defects resulting from  vastectomies/lumpectomies following breast cancer. With breast cancer being the most common cancer affecting women worldwide, there is a clinical need for reconstructive strategies addressing current drawbacks and limitations.

The development of biomimetic materials able to promote proliferation and adipogenic differentiation have gained increasing attention for adipose reconstructive purposes. The aim of the current research project includes

(1) the development of biodegradable, gelatin-based hydrogel building blocks with photo-polymerizable groups focusing on step growth polymerization which can be applied as starting materials for the fabrication of 3D constructs;

(2) 3D printing of constructs with an adipogenic shell and an angiogenic core;

These structures will then be assessed on biocompatibility via in vitro and in vivo assays as well as differentiation potential. The project outcome could offer a shift towards a patient-specific 3D printed, minimally invasive reconstructive approach, that can potentially be safer and more cost-effective.

Acrylate-endcapped urethane-based polyethylene glycol polymers for post-surgical chronic rhinosinusitis treatment

Jan-Philip Zegwaart

Promotors: Prof. Peter Dubruel, Prof. Sandra Van Vlierberghe

Acrylate-endcapped urethane-based polyethylene glycol polymers for post-surgical chronic rhinosinusitis treatment

Chronic rhinosinusitis (CRS) is a condition of perpetual inflammation of the sinuses in the nasal cavities, which affects about 15 % of the US and the European population. When drug treatments fail, surgical intervention is required. Draf III surgery is the final available option. During this procedure, a drainage pathway (neo-ostium) at the frontal sinus is created. Nonetheless, ostium closure still occurs in 22% of the cases.

The aim of the project is to develop a frontal sinus wound care solution using acrylate-endcapped urethane-based polymers (AUPs). AUPs are a promising type of macromonomers that allow the development of tailor-made polymer networks, including hydrogels, upon photo-crosslinking.

Within the project, 15 different types of AUPs were developed (subdivided into 4 categories). The AUPs are biocompatible, whereby the swelling and the material strength can be tailored. A second part of the research is focused on converting the AUPs into SLA resins, opening unprecedented 3D printing capabilities.

Future research on these AUP hydrogels entails drug-elution and in vivo testing, to advance the development of a superior frontal sinus wound care solution.

Other Grants and Projects

Smart biomaterials towards minimally invasive breast reconstruction

Coralie Greant

Promotor: Prof. Sandra Van Vlierberghe

Smart biomaterials towards minimally invasive breast reconstruction

The development of biomaterials for adipose regeneration has gained increasing attention as a result of the exponential growth of adipose tissue reconstructions performed in health care. In addition to cosmetic considerations, these reconstructions are also attempted for women undergoing lumpectomies after breast cancer  treatment, which is highly relevant as breast cancer is the most prominent cancer striking women worldwide. Recently, an increasing interest has emerged from material engineers to develop materials for adipose tissue engineering and breast reconstruction in particular, addressing the existing limitations. New biomaterial-related approaches should ideally aim for a more predictable outcome, an improved cost-effectiveness and minimal invasiveness. It is exactly there that the current project will come into play by combining patien-specific 3D printing with biodegradable shape memory polymers to replace the currently used invasive, artificial expander. These biodegradable smart polymers will then act as a support for autologous tissue injected into the pores.

BioMeniscus – Development of an artificial meniscus through 3D polymer printing

Martina Meazzo

Promotors: Prof. Peter Dubruel

Catherine Van Der Straeten (UZ Gent)

Prof. Fabrizio Barberis (Genoa University)

BioMeniscus - Development of an artificial meniscus through 3D polymer printing

The menisci are fibrocartilaginous structures that contribute to distribute compressive forces during joint movement, to static weight bearing, joint lubrication, joint stabilization and proprioception. For this reason, research into meniscus repair has been the recipient of particular interest from the orthopaedic and bioengineering communities because current repair techniques are only effective in treating lesions located in the peripheral vascularized region of the meniscus but not for non-vascularized region.

The primary method nowadays for treatment is still partial meniscectomy, which commonly results in the progressive development of osteoarthritis. This drawback has shifted research interest toward the fields of bioengineering and biomaterials.

The goal of BioMeniscus is to investigate the development of a novel meniscus implant based on a new type of polymer that mimics more accurately as possible the complicated meniscus structure.

One of the crucial features of a scaffolds is adequate mechanical properties. Therefore, one of the principal aims is to mechanically characterize them though different mechanical tests (compression test, tensile test, DMA, fatigue test, shear test etc). Some of these tests will be performed in collaboration with Genova University.

Acrylate-endcapped urethane-based polymers for the development of iodine-based antibacterial wound dressings

Georgios Misiakos

Promotor: Prof. Sandra Van Vlierberghe

Acrylate-endcapped urethane-based polymers for the development of iodine-based antibacterial wound dressings

The World Health Organization estimates that globally, burn injuries are responsible for

180,000 deaths every year. The leading cause of death in these cases is sepsis caused by infections. Iodine-based antibacterials are a potential successor to silver due to a lack of bacterial resistance and allergies, an efficacy against biofilms and covering a broad spectrum against microorganisms, however reapplication is needed every 12 to 24 hours.

Scaffolds with an ability to withhold iodine and release it gradually, would eliminate the major drawback of this antibacterial approach, which is the goal of this project. To this end, the manufacturing of acrylate-endcapped urethane-based polymer (AUP) sheets through electrospinning is employed. AUPs offer the novel ability of crosslinking in the solid state which opens up new pathways in the development of materials and the tuning of their properties. In addition, the method of electrospinning enables the creation of highly porous scaffolds with the potential to have sufficient mechanical robustness, while having the ability to uptake iodine and release it in a favorable timeframe.

3D Biomimetic model of the host-microbiome small intestinal
ecosystem

Inez Roegiers

Promotors:

Prof. dr. ir. Tom Van de Wiele (CMET)

Prof. dr. Peter Dubruel (PBM)

dr. Tom Gheysens (PBM)

dr. Marta Calatayud Arroyo (CMET and Prodigest)

3D Biomimetic model of the host-microbiome small intestinal ecosystem

The 3D intestine project aims to develop an in vitro model resembling the small intestine microenvironment and architecture, including human microbiota and the host interface and thus, cover the technological gap of mimicking the small intestine ecosystem in vitro. Our model will allow the research community and industry sector to evaluate in vitro the oral bioavailability of drugs or food compounds and simultaneously assess the microbial, host and environment interactions. The combination of fundamental insights from microbiology, human physiology, cell cultures and reactor

technology will be integrated in a multidisciplinary approach to attain as the main deliverable a reproducible model with a broad range of applications. This model will provide quantitative parameters to evaluate not only host parameters (e.g. epithelial barrier function, immune response) but also functional and structural microbiome shifts. In addition to the commercial importance of this research, the project will also contribute significantly to the scientific understanding of microbial-human interactions and its relevance for health. The project maximizes expertise from many labs to ensure excellence in the science outcomes of the project. The applicability of this model to pharmaceutical and nutrition industry and also for basic research will generate new knowledge and also a highly applicable outcome.

RELFICOM – Reliability of fibre-reinforced composites: materials design and variability

Babs Van De Voorde

Promotor: Prof. Sandra Van Vlierberge

RELFICOM – Reliability of fibre-reinforced composites: materials design and variability

Reliability is a vital concern in the composite industry, as most composite structures are designed not to fail under any circumstance. It is therefore vital to design parts close to the actual material performance. An alternative is to design the microstructure (1) to better cope with the expected stress concentrations and loads or (2) to exhibit a gradual or ductile failure behaviour, which will help to avoid complete dislodging of the part. RELFICOM therefore aims to achieve a breakthrough in the reliability of fibre reinforced composites, through improved material design and through better understanding and

controlling variability. This will lead to reductions in safety factors, and hence lighter and safer composite structures. RELFICOM also aims to improve the recyclability of composites by using/developing microtow filaments based on recycled polyethylene terephthalate (PET).

The proposed improvements are important to the Flemish industry, as proven by the fact that RELFICOM has attracted various industrial partners (REIN4CED, TWE, Toyota Motor Europe, Optimum CPV and Siemens Industry Software).

REFLICOM

Development of biodegradable polymers for controlled release of organic fertilizers

Evelien Vermosen

Promotors: Prof. Sandra Van Vlierberghe, Prof. Pascal Boeckx

Baekeland VLAIO project

VLAIO is the “Flemisch agency for innovation and entrepreneurship”. They encourage and support innovation, entrepreneurship, and contribute to a business climate. They give researchers and companies the opportunity to combine research and development. In the Baekeland project of Evelien Vermoesen the fertilizer company Fertikal n.v. is looking for the development a slow release biodegradable coating for organic fertilizers. Reactive nitrogen causes large environmental problems. The natural abundance of reactive nitrogen exceeded a long time ago. Resulting in a range of cascade – effects throughout the earth atmosphere: eutrophication, contamination of drinking water and soil, ozone, photochemical air pollution, acidification, toxic algae growth, … This resulted in large disturbance of the worlds ecosystem. Hence, the world is in need of organic fertilizers, and more, in need of a controlled release organic fertilizer. In this research fertilizers are coated with functional polymers aiming to control the nitrogen release and to enhance the nitrogen use efficiency of crops and plants. For this, nitrate and ammonium release studies will be done with consistent degradation measurements of the polymer coating.

This project is a collaboration between the ISOFYS - and the PBM research group at Ghent University. ISOFYS is equipped with diverse state-of-the-art stable and radioisotope analytical equipment and carries out highly international oriented research and education on isotope biogeochemistry, climate change mitigation and adaptation, and integrated tropical soil fertility. Doing so ISOFYS contributes to a process-based understanding of ecosystem functions.

PBM research group is specialized in the development of polymers for diverse applications ranging from functional polymers for biomedical applications, biocompatible coatings, advanced drug/gene delivery systems, scaffolds for tissue engineering, biosensor and polymers for optical applications. With this combined expertise, the goal is to develop an organic coated fertilizer which enables an aligned release of nutrients in combination with the growth of the plant.

For this a patented platform with AUP polymers is used. These are acrylate endcapped urethane based polymers. For this specific project biodegradability is of utmost importance while at the same time the coating needs to be strong enough to enable controlled release. The platform enables to work with variable polymer compositions to ensure both biodegradability and slow release of nutrients from the fertilizer.