Thoene-Reineke, C. | bioRxiv Science

bioRxiv2022

A Buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72h in mouse femoral fracture models

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are only available in the USA and have limited duration of action. Recently, a new microparticulate Buprenorphine formulation (BUP-Depot) for sustained release has been developed as an alternative product within Europe. Pharmacokinetics indicate a potential effectiveness for about 72h. Here, we investigated whether the administration of the BUP-Depot ensures continuous and sufficient analgesia in two mouse femoral fracture models and could therefore serve as a potent alternative to the application of Tramadol via drinking water. Both protocols were examined for analgesic effectiveness, side effects on experimental readout, and effects on fracture healing outcomes in male and female C57BL/6N mice. The BUP-Depot provided effective analgesia for 72h, comparable to the effectiveness of Tramadol in drinking water. Fracture healing outcome was not different between analgesic regimes. The availability of a Buprenorphine depot formulation for laboratory animals in Europe would be a beneficial addition for extended pain relief in mice, thereby increasing animal welfare.

animal behavior and cognition↗

bioRxiv2020

An in vitro human-based fracture gap model - Mimicking the crosstalk between bone and immune cells

The interaction between the bone and immune cells plays a crucial role in bone pathologies such as disturbed fracture healing. After a trauma, the initially formed fracture hematoma in the fracture gap contains all important components (immune/stem cells, mediators) to directly induce bone regeneration and is therefore of great importance but most susceptible to negative influences. Thus, reliable in vitro models are needed to study the underlying mechanisms and to predict the efficiency of novel therapeutic approaches. Since common bioengineering approaches exclude the immune component, we introduce an in vitro 3D fracture gap model which combines scaffold-free bone-like constructs with a fracture hematoma model consisting of human peripheral blood (immune cells) and bone marrow-derived mesenchymal stromal cells. Our in vitro 3D fracture gap model provides all osteogenic cues to induce the initial bone healing processes, which were further promoted by applying the osteoinductive deferoxamine (DFO). Thus, we were able to distinctly mimic processes of the initial fracture phase and demonstrated the importance of including the crosstalk between bone and immune cells.

bioengineering↗