Which kinds of innovations make for incremental enhancements in the hands of large companies and which are meaningful enough to sustain a venture-backed start-up company? In a mature market for coronary stents dominated by large companies, start-ups developing new stents need to find the answers. Areas of innovation fall into four basic categories: improving stent safety and biocompatibility, avoiding the need for dual antiplatelet therapy, enhancing deliverability, and introducing specialty stents for complex vessels. Three companies profiled here have a plan for taking sufficient market share, reducing risk, and rewarding investors.

Most medical device start-ups seeking to tap into the enormous drug-eluting stent market have focused on novel stent or stent platform design, on the theory that drug efficacy is a given. But X-Cell Medical is betting that they've come up with a better drug. And they're making their case by stressing the importance of safety.

X-Cell Medical's mission is to discover and develop alternative drugs for device-drug combinations, believing that the drug in such combination products is the most valuable component. The company has in-house expertise in drug discovery, formulation, and polymer coatings, as well as a deep set of cardiovascular device experience, coming from its medical advisory board, which consists of some of the most influential cardiology device users in the world.

Convergence is the great hope of pharmaceutical and device companies hoping to enter into new high growth markets with differentiated products. Drug-eluting stents turned a stagnant product into a thriving $6 billion market, and now companies are trying to find the next large opportunity that combines devices and drugs. They're looking at many kinds of implantable devices that incorporate biomaterials and drugs to achieve site specific drug delivery, in cardiovascular disease, peripheral vascular disease, ophthalmology, orthopedics, wound healing, and anti-infection.