Bioartificial organs in the twenty-first century: nanobiological devices

Bioartificial organs involve the design, modification, growth and maintenance of living tissues embedded in natural or synthetic scaffolds to enable them to perform complex biochemical functions, including adaptive control and the replacement of normal living tissues. Future directions in this area will lead to an abandonment of the trial-and-error implant optimization approach and a switch to the rational production of precisely formulated nanobiological devices. This will be accomplished with the help of three major thrusts: (1) use of molecularly manipulated nanostructured biomimetic materials; (2) application of microelectronic and nanoelectronic interfacing for sensing and control; and (3) application of drug delivery and medical nanosystems to induce, maintain, and replace a missing function that cannot be readily substituted with a living cell and to accelerate tissue regeneration. Biomimetics involves employment of microstructures and functional domains of organismal tissue function, correlation of processes and structures with physical and chemical processes, and use of this knowledge base to design and synthesize new materials for health applications. Nanostructured materials should involve biological materials (rather then synthetic ones) because their prefabricated structure is suitable for modular control of devices from existing materials. Nanostructured tools should encompass surface patterned molecular arrays, nanoscale synthetic scaffolding mimicking the cell-extracellular matrix microenvironment, precise positioning of molecules with specific signals to provide microheterogeneity, composites of bioinorganic and organic molecules, molecular layering (coating), and molecular and supramolecular self-assembly and self-organization (template-directed) assembly. The nanoelectronic interface includes electronic or optoelectronic biointerfaced devices based on individual cells, their aggregates and tissues, organelles, and molecules, such as enzyme-based devices, transport and ion-channel membrane proteins, and receptor-ligand structures, including nanostructured semiconductor chips and microfluidic components. Delivery nanosystems encompass both water and lipid core vehicles (for hydrophilic and lipophilic components) of various geometries: liposomes, micelles, nanoparticles, lipid shells (as imaging and contrasting agents), solid nanosuspensions, lipid nanospheres, and coated film surfaces (molecular layering), all for use in delivering drugs, proteins, cell modifiers, and genes. Nanoelectronic interface and delivery nanosystems will be used for sensing, feedback, control, and analysis of function of bioartificial organs.