Integration of drug, protein, and gene delivery systems with regenerative medicine

Regenerative medicine has the potential to drastically change the field of health care from reactive to preventative and restorative. Exciting advances in stem cell biology and cellular reprogramming have fueled the progress of this field. Biochemical cues in the form of small molecule drugs, growth factors, zinc finger protein transcription factors and nucleases, transcription activator-like effector nucleases, monoclonal antibodies, plasmid DNA, aptamers, or RNA interference agents can play an important role to influence stem cell differentiation and the outcome of tissue regeneration. Many of these biochemical factors are fragile and must act intracellularly at the molecular level. They require an effective delivery system, which can take the form of a scaffold (e.g., hydrogels and electrospun fibers), carrier (viral and nonviral), nano- and microparticle, or genetically modified cell. In this review, we will discuss the history and current technologies of drug, protein, and gene delivery in the context of regenerative medicine. Next, we will present case examples of how delivery technologies are being applied to promote angiogenesis in nonhealing wounds or prevent angiogenesis in age related macular degeneration. Finally, we will conclude with a brief discussion of the regulatory pathway from bench to bedside for the clinical translation of these novel therapeutics.