Engineering Bony Hybrid Organs In Vitro

摘要

Hybrid bony organs containing mineralized tissue, marrow and microcirculatory compartments could provide extremely novel and life-saving biosensors and tissue replacements. Previous progress in engineering distinct elements of bone suggests this more complex goal is feasible, but the challenges of integrating these elements into a single organ remain to be addressed. We are exploiting recent advances in stem cell biology, materials sciences, and microfabrication to create complex, multi-component bony organs. Materials presenting nanoscale-organized cell adhesion ligands and localized availability of growth factors have been developed, based on a combination of theoretical and experimental studies, to control the proliferation and differentiation of multipotent stem cells. This control is being exploited to create tissues in vitro within microfluidic systems that compartmentalize the cells and regulate their access to nutrients and waste exchange. Hematopoietic stem cells (HSCs) are being subsequently introduced into the engineered bony organs in an effort to establish functional blood cell forming organs. These engineered bone marrow organs could provide an unusually sensitive physiological biosensor for the presence of various toxic agents. Moreover, these organs could be customized for transplantation into individual soldiers requiring reconstitution of their bone marrow. The technologies developed to create these organs may also provide a template for the engineering of other complex, hybrid organs comprised of multiple cell types (e.g., liver, neural tissues) that would be useful for directly addressing trauma or promoting regeneration of damaged tissues and organs.