The molecular and physical information coded within the extracellular milieu is informing the development of a new generation of biomaterials for tissue engineering. Several powerful extracellular influences have already found their way into cell-instructive scaffolds, while others remain largely unexplored. Yet for commercial success tissue engineering products must be not only efficacious but also cost-effective, introducing a potential dichotomy between the need for sophistication and ease of production. This is spurring interest in recreating extracellular influences in simplified forms, from the reduction of biopolymers into short functional domains, to the use of basic chemistries to manipulate cell fate. In the future these exciting developments are likely to help reconcile the clinical and commercial pressures on tissue engineering.
Mineralization is a ubiquitous process in the animal kingdom and is fundamental to human development and health. Dysfunctional or aberrant mineralization leads to a variety of medical problems, and so an understanding of these processes is essential to their mitigation. Osteoblasts create the nano-composite structure of bone by secreting a collagenous extracellular matrix (ECM) on which apatite crystals subsequently form. However, despite their requisite function in building bone and decades of observations describing intracellular calcium phosphate, the precise role osteoblasts play in mediating bone apatite formation remains largely unknown. To better understand the relationship between intracellular and extracellular mineralization, we combined a samplepreparation method that simultaneously preserved mineral, ions, and ECM with nano-analytical electron microscopy techniques to examine osteoblasts in an in vitro model of bone formation. We identified calcium phosphate both within osteoblast mitochondrial granules and intracellular vesicles that transported material to the ECM. Moreover, we observed calcium-containing vesicles conjoining mitochondria, which also contained calcium, suggesting a storage and transport mechanism. Our observations further highlight the important relationship between intracellular calcium phosphate in osteoblasts and their role in mineralizing the ECM. These observations may have important implications in deciphering both how normal bone forms and in understanding pathological mineralization.biomineralization | crystallinity | mineral transport | electron energy-loss spectroscopy
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