Dr. Johannes R. Schmidt (Leipzig, DE), Vivien Wiltzsch (Leipzig, DE), Daniela Dias (Berlin, DE), Klaudia Adamowicz (Hamburg, DE), Chit Tong Lio (Hamburg, DE; Freising-Weihenstephan, DE), Lis Arend (Hamburg, DE; Freising-Weihenstephan, DE), Dr. Jörg Lehmann (Leipzig, DE), Dr. Thomas Lingner (Goettingen, DE), Dr. Olga Tsoy (Hamburg, DE), Dr. Tanja Laske (Hamburg, DE), Dr. Patrina S.P. Poh (Berlin, DE), Prof. Dr. Jan Baumbach (Odense, DK; Hamburg, DE), Prof. Dr. Stefan Kalkhof (Leipzig, DE; Coburg, DE)
Abstract text (incl. figure legends and references)
Although Type 2 diabetes mellitus (T2DM) can lead to compromised fracture healing, the extent to which it affects each patient is highly individualized. Yet, there is no biomarker profile available that can identify diabetes patients at risk. Additionally, the molecular mechanisms that lead to impaired fracture healing in diabetic conditions are not fully understood. The SyMBoD project aims to collect, automatically process and share molecular profiles on a digital platform in order to understand the molecular principles in high-risk patients and provide specific treatment. The ultimate goal is to develop image-guided personalized and functionalized polycaprolactone (PCL)-based scaffolds that can address the molecular needs at diabetic conditions.
Within this scope, a diabetic rat model was used to investigate PCL-guided bone regeneration in a femur defect. Blood plasma was sampled over 42 days post-surgery. Multiplexed proteomics screening analyses were carried out on a Q Exactive HF mass spectrometer. Proteins, that are specifically altered in the initial fracture response and subsequent regeneration phase were identified by (i) pairwise correlations of disease conditions and time points, (ii) time-aware biclustering and (iii) de novo network enrichment.
667 proteins were monitored in blood plasma over the sampling period of which 26 protein possess significant and diabetes-specific response profiles in comparison to non-diabetic animals. Preliminary integration of the results to tissue proteomics of the same animal cohort in combination with de novo network enrichment revealed proteins and functions that are likewise affected locally (in tissue) and systemically (in plasma). To the best of our knowledge, we report the first list of proteins that include altered proteins that are accessible from liquid biopsies and are directly or functionally linked to local effects. Those proteins may serve as indicative biomarkers to predict bone regeneration capacities.