Progress and Promise of Nitric Oxide‐Releasing Platforms

Abstract

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.

Nitric Oxide in Dental Pulp Tissue: From Molecular Understanding to Clinical Application in Regenerative Endodontic Procedures

“…Based on the tissues in which they are most prominently expressed, the following three distinct genes encoded NOS isozymes have been identified to date: neuronal NOS (nNOS or NOS I), inducible/immune NOS (iNOS or NOS II), and endothelial NOS (eNOS or NOS III). 11,24 The nNOS form is abundantly expressed in the brain and peripheral nerves, while eNOS is present mainly in endo-thelial cells; however, nNOS and eNOS expression is not restricted to neurons and endothelial cells, respectively. iNOS has been identified in a wide range of cells, such as bone cells, glial cells, and peripheral blood cells.…”

“…Currently, various biomaterials that have the potential to load and deliver NO in a sustained and/or controlled manner have been investigated that comprise hydrogels, nanoparticles and microspheres, nanoporous membrane, electrospun mats, and surface coatings; the combination of NO donors and these matrices may provide an occasion not only to control the release profiles of the donors but also to govern their cellular performances. 24,32,153 Stimulation of NO signals through mineral trioxide aggregate-like cements Biomaterials are foreign to the host, and the immune interactions between materials and tissues are very important for their biocompatibility evaluation and application. 16 Thus, copious basic and clinical evaluations of the immune response and odontoblastic differentiation of DPCs in response to different endodontic bioactive materials have been conducted.…”

Recent Advances in Manufacturing Innovative Stents

“…The NO-releasing nanoparticles are made of non-toxic biocompatible and biodegradable materials. For example, a chitosan polymer and optionally a sugar [106,107]. Patent US9878073 [105] demonstrates an example of such bioresorbable stents eluting nitric oxide (NO).…”

Bi‐Enzymatic Embolization Beads for Two‐Armed Enzyme‐Prodrug Therapy

“…Very recently, we and others have implemented SMEPT to achieve controlled synthesis of nitric oxide (NO), a potent signalling molecule with diverse, concentration‐ and tissue‐dependent physiological functions . The prime challenge of controlling delivery of NO lies in a very short lifetime of this two‐atom radical molecule.…”