Clay nanomaterials are an emerging class of two-dimensional (2D) biomaterials of interest due to their atomically thin layered structure, discotic charged characteristics and well-defined composition. Synthetic nanoclays are plate-like polyions composed of simple or complex salts of silicic acids with a heterogeneous charge distribution and patchy interactions. Due to their biocompatible characteristics, unique shape, high surface-to-volume ratio and charge distribution, nanoclays are investigated for various biomedical applications. This review article will provide a critical overview of the physical, chemical and physiological interactions of nanoclays with biological moieties including cells, proteins and polymers. The state-of-the-art biomedical applications of 2D nanoclay in regenerative medicine, therapeutic delivery and additive manufacturing are reviewed. In addition, recent developments that are shaping this emerging field are discussed and promising new research directions for 2D nanoclay-based biomaterials are identified.

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A nanoengineered bioink loaded with therapeutic proteins is designed to direct cell function in a 3D printed construct. The bioink is developed from a hydrolytically degradable polymer and 2D synthetic nanoparticle. The synthesis of poly(ethylene glycol)‐dithiothreitol (PEGDTT) via a Michael‐like step growth polymerization results in acrylate terminated degradable macromer. The addition of 2D nanosilicates to PEGDTT results in formation of shear‐thinning bioinks with high printability and structural fidelity. The mechanical properties, swelling kinetics, and degradation rate of 3D printed constructs can be modulated by changing the ratio of PEG:PEGDTT and nanosilicates concentration. Due to high surface area and charged characteristic of nanosilicates, protein therapeutics can be sequestered in 3D printing structure for prolong duration. Sustained release of pro‐angiogenic therapeutics from 3D printed structure, promoted rapid migration of human endothelial umbilical vein cell. This approach to design biologically active inks to control and direct cell behavior can be used to engineer 3D complex tissue structure for regenerative medicine.

We present a nanoengineered system for sustained and prolonged delivery of protein therapeutics, which has the potential to impact current orthopedic regeneration strategies. Specifically, we introduce two-dimensional nanosilicates with a high surface area and charged characteristics for delivery of active proteins for more than 30 days. The nanosilicates show high binding efficacy without altering the protein conformation and bioactivity. The released proteins are able to maintain high activity as demonstrated by enhanced differentiation of human mesenchymal stem cells at 10-fold lower concentration compared to the exogenous control. Utilizing the nanosilicates as a delivery vehicle could minimize the negative side effects observed because of the use of supraphysiological dosages of protein therapeutics for orthopedic regeneration strategies.

Organ-on-chips made of blood: personalized medicine with microfluidics.