The scientific interests of the Biomolecule Design Group balance between the disciplines of (bio)polymer chemistry, biochemistry and biotechnological engineering, the meeting place of materials science and life sciences.
The main focus of the group lies on the use and development of methods to chemically or biologically modify proteins, inspired by strategies found in nature. By manipulating the biological machinery of living cells, our group focusses on the development of functional protein-based materials.
One of the current goals is to ‘click’ biomolecules covalently and uniquely oriented onto functionalized solid substrates (diamond or conjugated polymers) in order to develop hybrid materials with improved, novel or well-defined biological functionality, reactivity and/or activity.
Our workhorse technique consists of the intein-mediated protein ligation that allows to purify and modify Nanobodies with bioorthogonal functional groups. To meet this challenge, BDG is equipped with a level 1 biosafety laboratory where recombinant proteins can be designed using molecular biological techniques and subsequently expressed in E.coli hosts.
The functionalised nanobodies can then be applied in a variety of biosensor applications owing to their high specificity, good thermal stability and small size.
A second research line is directed at the application of NMR-based techniques to identify altered metabolic pathways in cancer patients. By identifying those metabolites that show increased or decreased serum levels as compared to the the concentrations found in health volunteers, we can identify new biomarkers that can be used to quickly detect signs that may indicate the presence of a tumor. Since early detection of a tumor, will allow a more effective treatment, this work significantly improves the patient's prognosis.
By focussing on the proposed biomarkers, doctors will be able to assess if more invasive tests are required based on the results of a simple blood test. Moreover, by monitoring the biomarkers the effect of the prescribed chemotherapeutics can be evaluated, allowing oncologists to adapt their treatment if the desired results are not visible in the blood work.
Our biomaterials research line builds on the same principles and techniques used to prepare functionalised nanobodies. By engineering structural proteins and functional peptides, BDG is able to introduce new properties and functions to biomaterials. This research line was initially part of a new collaboration with the biomedical research institute (BIOMED), but has since spread to other applications. Today, the group's research interests focus on:
The development of cell interactive hydrogels is mainly responsible for the progress in tissue engineering over the past decades Today, the ideal hydrogel is considered to be a dynamic environment that answers the need of the developing tissue. With this in mind, it would be favourable to design hydrogels that remain stable during tissue development but fully degrade once the material has fulfilled its purpose. Previous research has attempted to control the biodegradation process by varying the cross-linking density or by providing competitive substrates for proteases. However, these approaches do not provide active control over the onset of degradation. In this project, we will translate the principles of prodrug development to peptide-based materials to enable direct control over the onset point of degradation, which may open up new avenues towards the development of dynamic biomaterials.
A heart attack leads to irreversible damage to the heart muscle. Current treatment methods mainly focus on the prevention of secondary infarcts and do not replace the lost cells. Consequently, a myocardial infarction often initiates a pathway leading to cardiac arrhythmias and heart failure. New stem cell therapies are under development, but are inhibited by the limited retention of these cells at the infarct site, which means that the majority of injected cells do not have ample time to differentiate into cardiomyocytes. Injectable hydrogels offer an elegant approach to increase stem cell retention. This project focuses on the development of elastin-like proteins that, in combination with oxidized hyaluronic acid, form dynamic networks. By combining both a protein and a carbohydrate component, the hydrogels will resemble the composition of the native extracellular matrix. The hydrogel network will be formed by reaction between aldehydes and hydrazines. In this reaction, reversible hydrazone bonds are formed that cause the materials to increase cell retention without impeding injectability. Moreover, by incorporating bioactive domains, the interaction with the encapsulated cells and the surrounding tissue will be improved. The physicochemical and biological properties of the hydrogels will be studied in detail in experiments mimicking their application as stem cell delivery vehicles.
The progress made over the past decades within the field of tissue engineering can mainly be attributed to the development of cell-interactive hydrogels. Such materials are no longer considered to be static scaffolds, as the research focus has instead shifted towards dynamic materials that can answer the needs of the developing tissue. The ideal scaffold should provide adequate mechanical support to the developing tissue and should therefore degrade at a rate corresponding to the rate of tissue formation. However, active control over the degradation rate remains a challenging objective. In this project, we will translate the principles of prodrug development to materials chemistry to enable direct control over the onset point of degradation, which may open up new avenues towards the development of dynamic biomaterials.
Degenerative diseases like osteoarthritis affect millions of people worldwide. Hybrid hydrogels show great promise in tissue engineering applications as scaffolds for supporting native cartilage that is damaged from arthritis. Such gels can be designed and synthesized to be biocompatible and have outstanding mechanical properties, approaching the remarkable behavior associated with native tissue. However, further improvement in function in the sense of promoting tissue regeneration is needed. Previous work has shown that (poly)peptide-polymer conjugates can be tailored to promote cellular interaction. Integrating peptides into hybrid hydrogels in a controlled manner remains a formidable challenge. This is particularly true in gels that exhibit stimuli-responsive behavior (e.g., triggered gelation) and are thus amenable to relevant processing such as injection and 3D bioprinting. All this must be achieved while also maintaining the necessary mechanical properties to support normal tissue function. This project addresses hydrogel design using an adaptable hybrid, dual network synthetic scaffold whereby the building blocks are functionalized for specific attachment to peptides. The mechanical properties will be tuned to match those of native cartilage and the processing and cellular interactions will be probed at the later stages of the Ph.D.
Continuous flow technology enables the synthesis of various complex organic chemicals (e.g. pharmaceuticals) with greatly improved efficiency compared with conventional multi-step batch synthesis. Translation of continuous flow principles to emerging polymerization techniques is still in its infancy. This is particularly true for novel photomediated polymerization protocols, whose fundamental process–reactivity relationships have only recently begun to be explored. As momentum builds in the field of controlled photopolymerizations of (cyclic) olefins and (cyclic) esters, a systematic merging of these approaches will enable access to structurally unique macromolecules. The aim of this project is to develop a fundamental understanding of how the process of state-of-the-art reactor technology for continuous flow polymerization influences polymer composition, topology, and function. This scalable technology will be explored for the process intensification of novel controlled photo-mediated polymerizations employing several orthogonal mechanisms including reversible deactivation radical polymerization (RDRP), ring-opening transesterification polymerization (ROTEP) and ring-opening metathesis polymerization (ROMP). Photomediated chemistry related to these various mechanisms remains at the forefront of current trends. They are ripe for further development, with high impact throughout the polymer community.
This project focusses on the use of the renewable, promising and abundant phenolic lignin biopolymer in the development of self-healing hydrogels with applications in the (bio)medical field. The pulping industry generates huge amounts of lignin as by-product, however, the majority is incinerated to recover bioenergy. Since lignin has a complex and yet not fully understood structure, it is not directly used as a high value reagent. This project will focus on the depolymerisation of lignin to obtain oligolignin which will undergo hydroxyalkylation followed by reversible boronate ester formation to finally obtain a self-healing oligomeric lignin-based hydrogel.
The heart attack is a cardiovascular disease, in which heart tissue dies due to a lack of oxygen. This loss of viable tissue can disturb the heart's function and lead to heart failure (HF), which is often fatal. Current therapies only slow down the progression towards HF. A potential cure aims at replacing the lost heart tissue with healthy tissue derived from stem cells. Researchers from Hasselt University have patented a new population of stem cells, the cardiac atrial appendage stem cells (CASCs). These CASCs show improved differentiation potential towards mature cardiomyocytes and are therefore promising candidates for heart tissue regeneration. However, CASC therapy is hampered due to the limited retention of stem cells at the transplantation site. This project focusses on developing shear-thinning hydrogels that facilitate CASC transplantation with increased on-site retention. The envisioned hydrogels mimic the natural environment of heart muscle cells by relying on a protein as well as a carbohydrate component. The synthetized protein is selected for its thermoresponsive nature and possibility to incorporate peptides for cell-interaction. While the carbohydrate has positive biological functions and is easily modified. Both components can be cross-linked via reversible hydrazone bonds to obtain an injectable hydrogel. The goal is to increase the hydrogels' mechanical and biological properties by additional cross-linking. The materials are expected to form biocompatible hydrogel networks, without impeding injectability.
An overview of the group's finished projects can be found here.
Besides playing a role in the development of biosensors and bio-inspired materials, our research projects can be central to numerous other applications including bio-imaging, peptide/polymer hybrids, improving biocompatibility of biomedical implants or targeted drug delivery systems.
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