Micro-fabrication and nano-technology offer unprecedented opportunities for control over the architecture material properties, and function of engineered systems with component sizes as small as tens of nanometers. With such accuracy and latitude in the control of multiple parameters, micro-fabricated systems present themselves as primate candidates for the development of innovate models of investigation of biological phenomena. On these premises, the field of Biomedical Microdevices (BioMEMS) has been expanding very rapidly, in recent times. In this project, BioMEMS technology is utilized in the study of cell structure and function, and the analysis of physical aspects of the interaction of cells with their surrounding biochemical environment. What is proposed is a platform multi- functional cell culture technology that is expected to be of use for a multitude of studies on cell structure, function, and biochemical interactions. For the same of specificity, the technology will be applied to two systems which address both structure-function relationships and biophysical interactions. The first system proposed herein is a micro- and nano-fabricated silicon- based environment replicating the architecture of cortical bone, and featuring an accurate dimensional reproduction of its substructures. No accurate artificial reproduction of the cortical bone has been made available in the literature to date, largely due to the absence of technology capable of yielding the relevant nanometer-size features of interest. The proposed silicon bone model is to be employed for the investigation of the role of osteocytes in mechanotransduction and bone remodeling-both subjects of outstanding interest in the scientific community, and in clinical practice. With a demonstrated ability to yield high-density arrays of pores with dimensions in the tens-of-nanometer range, or nano-fabricated bioseparation membrane technology is ideally suited for the investigation of cell-environment interactions. Thus, silicon-based cell culture wells will be used investigate the immunoisolation of cell transplants, specifically islet xenografts. By activating different per-selectivity criteria (size, surface chemistry, surface potentials), it is expected that the physical foundations of immunomolecular transport across membranes will be better understood, paving the way for possible advances in the field of immunoisolated cell xenograft-based therapeutics of diabetes mellitus and other pathologies. The advantage of the proposed technology in this context are the absolute precision in pore size, the ability to provide multiple perm-selective capabilities to the membrane (size, chemistry, potential), and the ability to conjugate a wide range of moieties to the capsule surfaces insufficient control over these factors has contributed significantly to the limited clinical success experienced by conventional polymer-matrix immunoisolative cell encapsulation technologies.
