3D Mineralized Bone Constructs

One of the central objectives of this project was the development and characterization of a 3D mineralized tissue model system in which the effects of mechanical load (e.g., compression loading, tension, vibration, etc.) on the cellular responses of osteoblasts and osteoclasts could be investigated. After introducing mineralization agents to the culture, the constructs take on a bone-like appearance and have a more rigid structure suitable for being tested. Testing of the mineralized constructs confirmed the presence of calcium through a crystalline matrix histochemical stain. The central core is void of necrotic material, instead filled by a crystalline matrix with embedded nucleated cells. Remarkably, the nucleated cells do not express osteoblast markers, indicating differentiation to the in vivo cell type known as the osteocyte. In addition, as is characteristic to native periosteum, osteoclast precursor cells were imaged and proven to naturally arrange as an outer layer of the mineralized bone tissue construct. Development of this model will provide a unique venue for testing proposed countermeasures to space flight-induced bone loss. It will also allow a mechanistic approach in the modulation of cell signaling at the cellular level within the bone matrix. The Development And Characterization Of A Three-Dimensional Tissue Culture Model Of Bone is a technology readiness level (TRL) 6 (system/subsystem prototype demonstrated in a relevant environment). The innovation is now available for your company to license. Please note that NASA does not manufacture products itself for commercial sale. Innovators at NASA Johnson Space Center have developed a technique to grow 3D tissue constructs, similar to human bone, in a laboratory environment. Problems arise when studying both the normal state and pathophysiology of bone. As an organ system, it is slow growing, so the time to study and observe a response to a particular stimulus is relatively long. Our bioengineers have discovered that osteoblast and osteoclast cell types can be induced to aggregate into large spheroids in a specific spatial relationship under certain culture conditions when placed in a rotating-wall tissue-culture vessel (shown above). The ability to construct a 3D model of such mineralized tissue on-demand, using a co-culture of human cells that differentiate and spatially arrange themselves in a physiologically relevant manner, is a major step forward in how the process of bone formation and remodeling can be studied.