Progress and Promise of Nitric Oxide-Releasing Platforms

Nitric oxide (NO) is a highly potent radical with a wide spectrum of physiological activities. Depending on the concentration, it can enhance endothelial cell proliferation in a growth factor-free medium, mediate angiogenesis, accelerate wound healing, but may also lead to tumor progression or induce inflammation. Due to its multifaceted role, NO must be administered at a right dose and at the specific site. Many efforts have focused on developing NO-releasing biomaterials; however, NO short half-life in human tissues only allows this molecule to diffuse over short distances, and significant challenges remain before the full potential of NO can be realized. Here, an overview of platforms that are engineered to release NO via catalytic or noncatalytic approaches is presented, with a specific emphasis on progress reported in the past five years. A number of NO donors, natural enzymes, and enzyme mimics are highlighted, and recent promising developments of NO-releasing scaffolds, particles, and films are presented. In particular, key parameters of NO delivery are discussed: 1) NO payload, 2) maximum NO flux, 3) NO release half-life, 4) time required to reach maximum flux, and 5) duration of NO release. Advantages and drawbacks are reviewed, and possible further developments are suggested.