Rational design and protein engineering of growth factors for regenerative medicine and tissue engineering.

Growth factors provide key instructive cues for tissue formation and repair. However, many natural growth factors are limited in their usefulness for tissue engineering and regenerative applications by their poor retention at desired sites of action, short half-lives in vivo, pleiotropic actions and other features. In the present article, we review approaches to rational design of synthetic growth factors based on mechanisms of receptor activation. Such synthetic molecules can function as simplified ligands with potentially tunable specificity and action. Rational and combinatorial protein engineering techniques allow introduction of additional features into these synthetic growth molecules, as well as natural growth factors, which significantly enhance their therapeutic utility.