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The incorporation of nanotechnology in regenerative medicine is at the nexus of fundamental innovations and early‐stage breakthroughs, enabling exciting biomedical advances. One of the most exciting recent developments is the use of nanoscale constructs to influence the fate of cells, which are the basic building blocks of healthy function. Appropriate cell types can be effectively manipulated by direct cell reprogramming; a robust technique to manipulate cellular function and fate, underpinning burgeoning advances in drug delivery systems, regenerative medicine, and disease remodeling. Individual transcription factors, or combinations thereof, can be introduced into cells using both viral and nonviral delivery systems. Existing approaches have inherent limitations. Viral‐based tools include issues of viral integration into the genome of the cells, the propensity for uncontrollable silencing, reduced copy potential and cell specificity, and neutralization via the immune response. Current nonviral cell reprogramming tools generally suffer from inferior expression efficiency. Nanomaterials are increasingly being explored to address these challenges and improve the efficacy of both viral and nonviral delivery because of their unique properties such as small size and high surface area. This review presents the state‐of‐the‐art research in cell reprogramming, focused on recent breakthroughs in the deployment of nanomaterials as cell reprogramming delivery tools.

Nanoparticles are popular delivery vehicles, but their diffusional release results in inconstant drug delivery. Here, we flatten the delivery profile into a more constant, zero-order profile. Brain-derived neurotrophic factor (BDNF) is attached to photoactive titanium dioxide nanoparticles and loaded into a nanofibrous self-assembling peptide (SAP) hydrogel. Different UV exposure conditions show three distinct profiles, including a counterintuitive decrease in release after UV exposure. We propose that the adsorption of the freed growth factor onto the hydrogel nanofibers affects release. Nanoparticles diffuse from the hydrogel readily, carrying the bound growth factor, but the freed growth factor (released from the nanoparticles by UV) instead interacts withand is released less readily fromthe hydrogel. UV shifts growth factor from nanoparticles to the hydrogel, therefore changing the diffusional release. Through midpoint UV exposure, we achieve a flattened delivery profileunusual for diffusionby changing in situ the amount of growth factor bound to the diffusing nanoparticles. With nanoparticle diffusion alone, we observed an increasing release profile with 36% of release in the first 6 h and 64% in the second 6 h. With midway UV exposure, this was controlled to 49 and 51%, respectively. The release of an unbound (soluble) control growth factor, glial cell-line derived neurotrophic factor (GDNF), was not affected by UV treatment, demonstrating the potential for independent control of temporal delivery profiles in a multiagent material.

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