Ex vivo Bone Models and Their Potential in Preclinical Evaluation

Abstract

Purpose of Review Novel therapies for damaged and diseased bone are being developed in a preclinical testing process consisting of in vitro cell experiments followed by in vivo animal studies. The in vitro results are often not representative of the results observed in vivo. This could be caused by the complexity of the natural bone environment that is missing in vitro. Ex vivo bone explant cultures provide a model in which cells are preserved in their native three-dimensional environment. Herein, it is aimed to review the current status of bone explant culture models in relation to their potential in complementing the preclinical evaluation process with specific attention paid to the incorporation of mechanical loading within ex vivo culture systems. Recent Findings Bone explant cultures are often performed with physiologically less relevant bone, immature bone, and explants derived from rodents, which complicates translatability into clinical practice. Mature bone explants encounter difficulties with maintaining viability, especially in static culture. The integration of mechanical stimuli was able to extend the lifespan of explants and to induce new bone formation. Summary Bone explant cultures provide unique platforms for bone research and mechanical loading was demonstrated to be an important component in achieving osteogenesis ex vivo. However, more research is needed to establish a representative, reliable, and reproducible bone explant culture system that includes both components of bone remodeling, i.e., formation and resorption, in order to bridge the gap between in vitro and in vivo research in preclinical testing.

Evaluating material-driven regeneration in a tissue engineered human in vitro bone defect model

“…However, the multicellular environment also complicates unraveling cell-material interactions. Thereby, keeping bone explants viable over time outside the living body remains a challenge [13,50]. Cell death in explants transplanted in a different host as described above may trigger a nonphysiological regeneration/remodeling response.…”

“…Thus, both the translation from in vitro assessments to in vivo models and the translation from in vivo animal models to the human clinic need to be improved. To address these translational issues and improve preclinical graft testing, advanced human in vitro bone defect models should be developed and integrated into the preclinical graft testing routine [12][13][14]. For the creation of such in vitro models, traditional bone tissue engineering strategies can be applied [15].…”

Evaluating material-driven regeneration in a tissue engineered humanin vitrobone defect model

“…However, the multicellular environment also complicates unraveling cell-material interactions. Thereby, keeping bone explants viable over time outside the living body remains a challenge [13,46]. Cell death in explants transplanted in a different host as described above may trigger a non-physiological regeneration/remodeling response.…”

The Embryonic Chick Femur Organotypic Model as a Tool to Analyze the Angiotensin II Axis on Bone Tissue

“…In this context, ex vivo systems emerge as useful tools with several advantages, namely the preservation of the 3D tissue cellular environment [ 31 ]. The embryonic chick limb organotypic model has been used in bone-related biology to address development, regeneration, and responses to external stimuli [ 32 , 33 ].…”