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Human bone model enables research on the genetic defect

In osteogenesis imperfecta, a genetic defect causes the protein collagen, which is crucially involved in bone formation, to be unable to form stable structures. As a result, the bones of affected individuals are extremely brittle, which is reflected in the colloquial term 'brittle bone disease.' Scientists at ETH Zurich have now developed a model that enables animal-free research on the disease (1).

There are over 20 animal models for brittle bone disease, primarily involving genetically modified mice and fish. Dogs are also used as so-called animal models (2). However, due to inter-species differences and the resulting lack of transferability of animal testing results to humans, no satisfactory therapy for the disease has yet been developed. Consequently, the disease continues to force many patients into wheelchairs due to bone deformations.

In contrast to so-called animal models, the newly developed bone model uses human cells, thus generating results relevant to humans. The model is based on a three-dimensional scaffold, in the pores of which bone-forming cells, known as osteoblasts, can settle. In the scaffold, the cells form a three-dimensional network. The scaffold material is designed to be degraded by specific proteins secreted by the cells. This allows the cells to shape their environment and build the so-called extracellular matrix, so the model closely mimics the natural development of human bone. Additionally, the material is perfused with a fluid, providing the cells not only with nutrients but also exerting shear forces similar to those occurring in the human body on the cells.

In the human bone model, cells from patients with brittle bone disease can now be used. This allows for detailed research on the disease and testing of new medications and therapies. Besides brittle bone disease, other bone diseases can also be replicated on the chip. Currently, the scientists are developing a model of osteoporosis (2).


(1) Zauchner D. et al. Synthetic biodegradable microporous hydrogels for in vitro 3D culture of functional human bone cell networks, Nature Communications 2024; 15:5027

(2) Walter N. Gaining a better understanding of brittle bone disease – without animal experiments, News, ETH Zurich, 13.06.2024 >>