Designing biomaterials with oriented organic nanocrystals for tissue engineering applications

The extracellular matrix (ECM) has a specific architecture that defines tissue mechanics and helps to guide cell functions. In tissue engineering, it is crucial to be able to mimic the architecture and mechanics of the ECM with biomaterials. However, mimicking the architecture and mechanics of tissues that contain ECM elements oriented at the nanoscale, such as articular cartilage, tendon, intervertebral disc, and cornea, remains challenging. To succeed, an emerging strategy is to orient nanocrystals within materials by using manufacturing techniques such as extrusion printing and magnetic induction. This strategy is increasingly used in tissue engineering where it can help to produce mechanically reinforced biomaterial scaffolds and spatially organize cells. This review introduces techniques that allow for orienting organic nanocrystals within materials and discusses their potential and limitations for tissue engineering applications. First, it presents an overview of the classes of organic nanocrystals used in tissue engineering, before summarizing the state of the art in the processing of oriented nanocrystals. Then, the use of materials containing oriented nanocrystals is discussed for two major applications, i.e., mechanical reinforcement and cell alignment. Finally, new avenues of research are proposed to advance this emerging class of materials toward biomedical applications. STATEMENT OF SIGNIFICANCE: In tissue engineering, one major challenge is to mimic the architecture of the cell microenvironment down to the nanoscale. To succeed, one strategy is to use fabrication techniques that allow the orientation of nanocrystals within materials. This review presents the state of the art in the design of biomaterials with oriented organic nanocrystals and discusses their potential in tissue engineering.