Bioengineered Hierarchical Bonelike Compartmentalized Microconstructs Using Nanogrooved Microdiscs

Fabrication of vascularized large-scale
constructs for regenerative
medicine remains elusive since most strategies rely solely on cell
self-organization or overly control cell positioning, failing to address
nutrient diffusion limitations. We propose a modular and hierarchical
tissue-engineering strategy to produce bonelike tissues carrying signals
to promote prevascularization. In these 3D systems, disc-shaped microcarriers
featuring nanogrooved topographical cues guide cell behavior by harnessing
mechanotransduction mechanisms. A sequential seeding strategy of adipose-derived
stromal cells and endothelial cells is implemented within compartmentalized,
liquefied-core macrocapsules in a self-organizing and dynamic system.
Importantly, our system autonomously promotes osteogenesis and construct’s
mineralization while promoting a favorable environment for prevascular-like
endothelial organization. Given its modular and self-organizing nature,
our strategy may be applied for the fabrication of larger constructs
with a highly controlled starting point to be used for local regeneration
upon implantation or as drug-screening platforms.