In this issue, two groups report progress in engineering bone for engraftment to treat bone defects. On page 954, Kale et al. report for the first time the ex vivo generation of crystalline human bone within a three-dimensional cellular matrix. In the presence of serum-free medium containing transforming growth factor β1 (TGF-β1), which is known to modulate early osteogenesis, the cells aggregated into “bone cell spheroids,” which then began producing bone-specific proteins, culminating in the formation of microspicules containing organized human bone.

On page 959, Petite et al. exploited the similarity of coral exoskeleton to the porous architecture of natural bone, using coral as a scaffold for marrow stromal cells expanded in vitro. These were implanted into relatively large (25 mm) defects in sheep metatarsals. They observed substantial regeneration in bone implanted with the coral–MSC implants, which exceeded that of coral alone or coral plus fresh bone marrow that had not undergone in vitro expansion. Both studies support an emergent theme in tissue engineering—that mimicking natural cellular interactions and three-dimensional environment is essential for in vitro tissue regeneration (See also p. 928).