Research

HUMAN PLACENTA Collagen-I from THT Biomaterials GmbH is a novel biomaterial that due to his human source alleviates the downstream limitations associated with the use of animal-derived materials in research. Although the intrinsic fibrillogenesis capacity of THT HUMAN PLACENTA Collagen-I has shown to be sufficient for 2D coating applications, his polymerization ability is limited for the formation of stable 3D hydrogel structures that are indispensable for physiologically relevant cell culture strategies. In this regard, Prof. Cornelia Kasper´s research lab from the Universität für Bodenkultur Wien BOKU has the necessary expertise to support THT in adjusting the mechanical properties of HUMAN PLACENTA Collagen-I to obtain stable and functional hydrogels. Prof. Cornelia Kasper´s research lab suggests to functionalize the HUMAN PLACENTA Collagen-I with methacrylate groups, a common strategy used to modify of different proteins or sugar-based biopolymers. The presence of methacrylate-groups will enable the introduction of covalent bonds upon exposure to UV in the presence of photoinitiators, thus forming hydrogels that can be used subsequent used for different 3D applications. The newly functionalized product (HUMAN PLACENTA Collagen-I methacrylate) will expand THT portfolio allowing his straightforward the use for customers working in different 3D biological applications such as 3D cell culture (e.g. organoids culture), lab-on-a-chip, bioprinting and thus broaden the current applicability of HUMAN PLACENTA Collagen-I. Significantly, the envisioned biomaterial can also be used as ready-to-use bioink for trendy technologies such as light-based 3D bioprinting. Apart from possible publications and co-authorships abstracts, THT & Universität für Bodenkultur Wien BOKU can potentially obtained IP on HUMAN PLACENTA Collagen-I methacrylate generating value for both project partners. If for any reason the innovation check should be cancelled, BOKU reserves the right to charge for services provided in the meantime.

Osteoarthritis (OA) represents a considerable societal and economic burden in today’s society. Despite the tremendous developments in the field of articular cartilage tissue engineering (AC TE) in the recent decade, none of the TE-based approaches has been able to regenerate the cartilage to levels of native tissue. The established paradigm of AC TE involves employment of undifferentiated MSCs in combination with 3D scaffolds/hydrogels and appropriate growth factors to induce chondrogenic differentiation of cells and deposition of ECM components like collagen and glycosaminoglycans. Once successful tissue has been formed in vitro, engineered cartilage grafts can be studied in vivo in large animal models to assess safety and efficacy of such grafts. Unfortunately, a considerable amount of grafts fails in vivo, which indicates the overall unsuitability and immaturity of the engineered tissues to function in the mechanically demanding environment of the joint in vivo. More importantly, there is no incentive to publish or submit for publication unsuccessful studies, which indicates that the number of failed studies employing large animal models could be considerably higher. Therefore, there is a need for novel strategies to screen and identify in vitro engineered cartilage grafts that have higher chances of success in vivo. In addition to increasing the success rate of such studies, this approach would have a great potential to reduce the number of animals utilized in such studies. In this context, there is evidence suggesting that chondrogenically differentiating MSCs respond anabolically to mechanical stress at later stages of differentiation by producing ECM components like glycosaminoglycans. Interestingly, the differentiation of MSCs is also associated with metabolic changes, where glycolysis is reduced and oxidative phosphorylation is enhanced as maturation progresses. The goal of this project is to develop a platform that could be used to assess such metabolic changes by sampling metabolites in- and outside the developing cartilage grafts to make statements concerning the maturity. By establishing such platform an additional readout would be available, in addition to commonly used biochemical and histological techniques within AC TE, that would facilitate a more informed decision making prior to an in vivo transition of a potential cartilage graft.

There is ample evidence linking gestational diabetes melitus (GDM) in utero with offspring obesity and the development of metabolic diseases later in life. Experimental evidence shows that GDM alters DNA methylation of placental and fetal cells. In addition, GDM alters the function of umbilical cord mesenchymal stem cells. However, nothing is known to date about the effects of GDM on MSC and MSC-derived adipocyte programming and resulting adipocyte (dys)function. The proposed project aims to fill this knowledge gap and determine whether GDM in pregnancy shapes the predisposition to obesity and dysfunctional adipose tissue in offspring through epigenetic programming of fetal MSC. Hypothesis: The intrauterine GDM environment reprograms fetal MSC and alters their function and differentiation capacity. This programming affects adipogenesis and stem cell-derived adipocytes in terms of paracrine activity, lipid composition, and insulin resistance. The main goal of this project is to uncover the programming effects of GDM on neonatal MSC and the resulting differential adipogenesis and adipocyte function. Specifically, we aim to determine the effects of maternal GDM on MSC and on differentiated MSC-derived adipocytes in terms of DNA methylation, the secretome, and its effects on angiogenesis, lipid and ganglioside composition, and insulin resistance.