Bionanofabrication: engineering biomaterials for in situ remodeling and drug delivery

Abstract

The bionanofabrication of smart materials presents opportunities in fields as far ranging as food science and medicine. The tools of molecular biology allow for the in vivo and in vitro production of unique biomolecules enabling not only the direct(ed) creation of novel proteins but also catalysts that can then produce other non-protein polymers. An example is the biodegradable polymer, polyhydroxyalkanoate (PHA), which is normally produced by a number of different bacteria. It is synthesized through a series of three enzymes but only one, polyhydroxalkanoate synthetase (PHAC) is required for the conversion of a soluble CoA-substrate into an insoluble hydrophobic polymer. Our laboratory has pioneered the in situ formation of PHA by engineering PHAC and targeting it toward fabricated and native substrates. Once on-site polymer formation can be initiated by introducing the substrate. Alternatively polymers can be formed in vitro and then delivered to the target site. Beyond the localized impact by the introduction of significant quantities of a highly hydrophobic polymer, PHA can also be used as a vehicle for the delivery of therapeutic drugs and once there release their cargo through its normal degradation process. Applications to cancer therapy and in situ engineering of microvasculature will be presented.