3D printed metamaterials: properties, fabrication, and drug delivery applications

Drug delivery is a process to deliver the required amount of a drug to a target site within an appropriate timeframe, while minimizing possible side effects and maximizing efficiency. This is accomplished by drug delivery systems (DDSs), which are platforms composed of natural and/or synthetic materials that carry drugs or bioactive agents at a particular site or throughout a patient's body via oral, transdermal, topical, intravenous, or intramuscular routes to minimize the drug's toxicity and provide desired therapeutic effects without affecting the patient's healthy cells, tissues or organs. Despite significant advancements, drug delivery still faces numerous scientific, technological, and clinical challenges, such as poor drug bioavailability, unstable loading efficiency, lack of site-specificity, undesired prolonged delivery of drugs. Issues such as drug stability, limitations in achieving controlled and sustained release, long-term unwanted toxicity, and patient compliance are also common challenges in the field. In recent years, researchers have created 'Metamaterials', which exploit the advancements in fabrication and 3D printing technology to exhibit complex characteristics and customizable architecture that are not otherwise naturally present in a material. These properties provide a precision control over drug release kinetics, targeting, and efficiency by precise manipulation of interactions at the nanoscale. This review explores the potential of metamaterials in developing advanced DDSs with exceptional precision and efficacy, via materials selection, design considerations, fabrication challenges, and optimization strategies for 3D printing of these materials. We provide an overview of their recent application in drug delivery tackling the challenges associated with release systems, including sustained, pulsatile, and on-demand delivery modalities. Targeted delivery, theranostic applications, and regenerative medicine, are also explored. We believe this review will inspire further research and development in this burgeoning field by highlighting the challenges associated with their biocompatibility, scalability, manufacturing considerations, and hurdles or opportunities in translation, ultimately leading to transformative advancements in personalized medicine and healthcare.