How the field of controlled-release technology began, and its central role in the development of angiogenesis...

The first controlled-release methodology was developed in 1962 and was based upon diffusion of small molecules (molecular weight less than 500) through the wall of silicone rubber tubing. The problem of controlled-release of large molecules such as proteins was not solved until more than a decade later, when it was discovered that microchannels formed around lyophilized proteins embedded in polymers such as ethylene vinyl acetate copolymer (EVA) and poly(hydroxyethylmethacrylate) (pHEMA), as water permeated through the polymer. These studies led to the development of a 5-year contraceptive implant, e.g., Norplant; rapid progress in the field of angiogenesis research; and a method for regulating cell shape and growth control in vitro.