Systems medicine approach for personalized bone defect treatment in patients comorbid with Type-2 diabetes (SyMBoD)

X-ray image of both hip showing femur fracture at left side
© praisaeng -

Our bones possess the remarkable feature to heal completely without forming fibrous scar tissue. However, different conditions may lead to a delayed, compromised or absent bone regeneration. Possible reasons could be a critical size fracture or systemic disease conditions, e.g. osteoporosis or type-2 diabetes mellitus (T2DM). In the latter case, tissue revascularization and differentiation of bone forming osteoblasts is often compromised. However, the extent of impaired healing capacities depends on each patient and until now, no diagnostic biomarker exists for prognosis of impaired bone healing before treatment begins. This often increases the burden of patients that suffer from non-healing fractures in standard therapies before a bone implant crafted from inert materials, autografts or allografts is applied. However, those materials are not optimal from different perspectives.

To this end, the SyMBoD projects aims to develop a digital platform for decision-making in treating patients with bone defects suffering from T2DM. This includes (ii) the identification of theranostic biomarkers and (ii) the modeling of individualized, patient- and fracture-specific scaffolds for fracture bridging. Therefore, different tissues (blood plasma and cells, bone tissue and exosomes) from both animal models and human biobanks will be screened in a multi-Omics approach to extract individual molecular profiles. Those profiles will be correlated to further clinical parameters and healing processes by AI-supported bioinformatic methods to stratify patients into risk groups and to identify theranostic biomarkers.

In parallel, bioresorbable polycarpolacton-based scaffolds will be optimized, based on multi-scaling modelling and iterative testing in animal models. This will allow for (i) optimizing biomechanical properties of the material at different size scales and (ii) developing computer models for the prediction of optimal individualized patient- and fracture-specific scaffolds.

Both, molecular and biomechanical models will be implemented into the platform and will guide clinicians (i) to identify risk patients based on selected prognostic biomarkers and (ii) to seamlessly create computer models of individualized scaffolds based on fracture imaging. Finally from those models, real bone implants can be manufactured in a GMP-compliant manner applying CAD-CAM 3-D printing techniques with biocompatible and resorbable materials breaking ground for personalized therapy in bone healing.

Project management
Prof. Dr. Stefan Kalkhof

Improving hookworm monitoring through the development of a rapid diagnostic test (“WormShield”)

The Ancylostoma caninum hookworm attached to the intestinal mucosa
© CDC’s Public Health Image Library
The Ancylostoma caninum hookworm attached to the intestinal mucosa.

Worm infections still present a major health-related challenge, especially in tropical and sub-tropical regions. According to statistics published by the Centers for Disease Control and Prevention in 2013, more than 700 million people around the globe are affected by hookworm infections alone, which cause up to 60 000 deaths per year. The infection is transmitted upon coming into contact with water or soil that has been contaminated with feces, which means that it mainly affects rural populations. The infection can be treated effectively with albendazole or mebendazole. The diagnostic methods used at present (Kato Katz, MiniFLOTAC, McMaster) require trained staff and a suitable diagnostic infrastructure, which is why many infections are not diagnosed until very late.

The aim of the international collaboration project “WormShield”, which sees the Proteomics Unit collaborate with the company BioScientia (Poland), Cayetano Heredia University (Peru) and Dr. Hugo Mendoza Pediatric Hospital (Dominican Republic), is to improve the diagnosis of hookworm infections in an everyday clinical setting by developing a quick, specific, sensitive, robust and easy-to-use lateral-flow assay. This test is then to be rolled out around the world as a point-of-care diagnostic tool.

The project is being funded by the EU as part of the EU-LAC Health initiative to promote cooperative health research with states from Latin America and the Caribbean.

Project management
Prof. Dr. Stefan Kalkhof

LowAllergen / FoodAllergen – Detection of plant-derived allergenic protein structures with subsequent modification and testing for the successful reduction of allergenic potential through analytical methods

The frequency of newly developed food allergies (incidence) is increasing worldwide. At the same time, a rise in non-conventional food ingredients – particularly plant-based ingredients – has been registered, following the modern trend of resource-conscious food. This trend has also been noted by European directives with the purpose of making consumers aware of the risk of allergies as well as protecting them from the consequences of allergies (LMIV). As a result, the demand for reliable methods to analyze allergenic ingredients as well as for the technology to reduce allergenic ingredients has grown significantly over the past few years.

The "LowAllergen" project and its follow-up project, "FoodAllergen", are concerned with plant-based allergenic food ingredients. One part of the project is geared towards changing proteins to the extent that their allergenic potential is decreased. The requirements for this are innovative technologies for modifying proteins which are developed in our partner institute Fraunhofer IVV. As part of the “Food Allergen” project, the Proteomics Unit is responsible for developing antibody-based test systems which enable a quantitative analysis of allergenic ingredients and reveal any remaining allergenic potential after applying allergen-reducing procedures. Using soy as an example, in the "LowAllergen" project, a decrease of allergenic components could be observed as a result of applying certain microorganisms in fermentation processes and hydrolysis using high pressure. In the "FoodAllergen" project, the processes and analytical methods will be expanded to other plant-based protein ingredients to implement technologies for modifying allergens as well as analytical methods for detecting successful reduction of allergens as soon as possible.

Project management
Dr. Jörg Lehmann

Development of diagnostic assays for detection of biomarkers in milk and blood for health control in dairy herds

In the field of ‘Biomarker-based veterinary diagnostics’ specific and sensitive diagnostic techniques based on immunological biomarkers are going to be developed for cattle. Screening tests verifying biomarkers are particularly appropriate to detect sick animals within the herds prior the occurrence of clinical symptoms. Positively diagnosed animals could supply veterinary examination in a targeting manner. Potentially, this approach could result in a medium-term increase in economic efficiency. Because animals’ health and well-being are closely related the development of biomarker tests contributes considerably to the principles of animals’ and consumers’ welfare.

In the project ‚On-Farm-Recording_Breeding‘ supported by the (former) Federal Ministry of Food, Agriculture and Consumer Protection, the Department of Therapy Validation has identified and characterized different biomarkers for health monitoring in cattle. A patent application submitted in 2015 is aimed at an international patent protection. The best performing biomarker candidates are currently under pre-commercial development at different stages. The final steps to reach marketability will be done in close collaboration with our industrial partners. A substantial benefit for the optimal diagnostic value is expected from the combined detection of biomarker through multiplex analysis. Together with partners in veterinary medicine, livestock breeding farms, and diagnostics industries we aim at the development of user-friendly products that will be well-accepted by farmers. Moreover, we seek to offer innovative product concepts that will suit the needs of a future-compliant agriculture.

The diagnostic assay for the detection of haptoglobin, a major acute-phase protein in cattle, is currently at the last stage of pre-commercial development, i.e. clinical validation. For the development of diagnostic assays for further interesting biomarker candidates we are searching for granting opportunities.

Project management
Dr. Anke Hoffmann, Dr. Jörg Lehmann

Completed projects

  • Project "Bronchial Carcinoma" as part of the BMBF program "Innovative Regional Growth Cores", "GC Potential" module