Academic Awards 2023 booklet

73 Advancing tissue engineering of in vitro human bone models Bone tissue engineering has traditionally been focusing on developing grafts for patients with large bone defects, making use of scaffolds, progenitor (parent) cells, biochemical and biomechanical stimuli (Figure 1). Nowadays, this method is increasingly applied for the creation of in vitro models that could facilitate the investigation of human bone while potentially reducing animal experiments. To mimic bone remodeling in the laboratory, cocultures of bone resorbing osteoclasts and bone forming osteoblasts are frequently used. However, conditions for these cocultures are often not sufficiently representing the human bone environment and are often optimized for only one cell-type. This can lead to unequal stimulation of osteoclasts and osteoblast, leading to unbalanced remodeling; a hallmark for bone remodeling pathologies. Here, tissue engineering methods to improve biomimicry of the to be remodeled matrix as well as the biochemical and biomechanical cell-culture environment were systematically refined. Moreover, non-invasive methods to track remodeling over time where applied (Figure 2). As a result, a human in vitro bone remodeling model was developed using an osteoclast- osteoblast coculture, helping to advance preclinical in vitro bone treatment development while potentially replacing animal experiments. Figure 1: Using the tissue engineering paradigm to develop an in vitro human bone remodeling model. Parts of figure drawn using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License. (https://creativecommons.org/licenses/by/3.0/) Figure 2: In vitro human bone remodeling in response to three different combinations of environmental cues. Remodeling was tracked using time-lapsed micro-CT scanning. Orange is bone formation by osteoblasts, blue is bone resorption by osteoclasts, grey is unchanged volume.