Biodegradable Cell Transplantation Devices for Tissue Regeneration
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BIODEGRADABLE CELL TRANSPLANTATION DEVICES FOR TISSUE REGENERATION Antonios G. Mikos1, Heidi L. Wald ,+, Georgios Sarakinos 2 , Susan M. Leite 1 , and Robert Langer' 1 Department of Chemical Engineering, Massachusetts Institute of Technology, Room E25-342, 77 Massachusetts Avenue, Cambridge, MA 02139 2 Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 +Current affiliation: Harvard Medical School, Boston, MA 02115 ABSTRACT Biodegradable polymers can be utilized as templates for cell transplantation and regeneration of metabolic organs and structural tissues. Candidate materials must be adhesive substrates for cells, promote cell growth and allow for retention of cell function. However, the processing requirements of such materials into highly porous three-dimensional structures with large surface per volume and an interconnecting pore network limits their potential application for tissue regeneration. A new processing technique was developed to produce uniform, three-dimensional cell transplantation devices of poly(lactic-co-glycolic acid). The process involved the preparation of highly porous membranes by a solvent-casting and particulate-leaching technique followed by their lamination. The device structural and mechanical properties depended on those of their constituent membranes, as evaluated by mercury porosimetry, scanning electron microscopy, and thermomechanical analysis. Cells to be seeded into the devices were injected from catheters incorporated within their structure. In vitro studies with model suspensions of dyed microspheres allowed for visual evaluation of the internal pore structure of various layered devices. From these studies, numerous parameters of device design for cell seeding were determined including pore size and injection rate. The membrane lamination technique produced devices without interfaces between layers as determined by microsphere injection and scanning electron microscopy.
Introduction The use of biodegradable polymers to regenerate metabolic organs, such as liver and pancreas, and repair structural tissues like cartilage and bone by cell transplantation was recently explored [1-4]. To create organ function, individual cells are harvested from donor tissue, the cells are attached to a suitable scaffold, and the construct is implanted at a site where the immobilized cells grow
and function. The three-dimensional scaffold serves as both a physical support and an adhesive substrate for isolated parenchymal cells during in vitro culture and subsequent implantation [3,5]. These scaffolds are designed to mimic their counterparts, the natural connective tissues of the body. Therefore, a successful cell transplantation support must exhibit a large number of diverse characteristics including high surface area to volume ratio, high percentage porosity, ease of processability into desired three-dimensional forms, and mechanical strength. In addition these polymers must be biocompatible, biodegradable, and allow expression of norma
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