Modular Assembly of Metamaterials Using Light Gradients.

This is a report on a pilot study that tests the feasibility of assembling photonic metamaterials (PMs) using light gradient forces. Following a strategy that works like modular construction, light gradient forces, produced by a tightly focused, 1D standing wave optical trap, time-multiplexed across a 2D lattice are used to assemble voxels consisting of prefabricated, monodispersed nanoparticles (NPs) with radii ranging from 30 to 500 nm into 3D structures on a hydrogel scaffold. Hundreds of NPs can be manipulated concurrently into a complex heterogeneous voxel this way, and then the process can be repeated by stitching together voxels to form a metamaterial of any size, shape, and constituency although imperfectly. Imperfections introduce random phase shifts and amplitude variations that can have an adverse effect on the band structure. Regardless, PMs are created this way using two different dielectric NPs, polystyrene and rutile, and then the near-infrared performance for each is analyzed with angle-, wavelength-, and polarization-dependent reflection spectroscopy. The cross-polarized spectra show evidence of a resonance peak. Interestingly, whereas the line shape from the polystyrene array is symmetric, the rutile array is not, which may be indicative of Fano resonance. So, even with the structural defects, reflection spectroscopy reveals a resonance.

Tissue engineered drug delivery vehicles: Methods to monitor and regulate the release behavior.

Tissue engineering is a rapidly evolving, multidisciplinary field that aims at generating or regenerating 3D functional tissues for in vitro disease modeling and drug screening applications or for in vivo therapies. A variety of advanced biological and engineering methods are increasingly being used to further enhance and customize the functionality of tissue engineered scaffolds. To this end, tunable drug delivery and release mechanisms are incorporated into tissue engineering modalities to promote different therapeutic processes, thus, addressing challenges faced in the clinical applications. In this review, we elaborate the mechanisms and recent developments in different drug delivery vehicles, including the quantum dots, nano/micro particles, and molecular agents. Different loading strategies to incorporate the therapeutic reagents into the scaffolding structures are explored. Further, we discuss the main mechanisms to tune and monitor/quantify the release kinetics of embedded drugs from engineered scaffolds. We also survey the current trend of drug delivery using stimuli driven biopolymer scaffolds to enable precise spatiotemporal control of the release behavior. Recent advancements, challenges facing current scaffold-based drug delivery approaches, and areas of future research are discussed.

Methacrylate-Modified Gold Nanoparticles Enable Non-Invasive Monitoring of Photocrosslinked Hydrogel Scaffolds.

Photocrosslinked hydrogels, such as methacrylate-modified gelatin (gelMA) and hyaluronic acid (HAMA), are widely utilized as tissue engineering scaffolds and/or drug delivery vehicles, but lack a suitable means for non-invasive, longitudinal monitoring of surgical placement, biodegradation, and drug release. Therefore, we developed a novel photopolymerizable X-ray contrast agent, methacrylate-modified gold nanoparticles (AuMA NPs), to enable covalent-linking to methacrylate-modified hydrogels (gelMA and HAMA) in one-step during photocrosslinking and non-invasive monitoring by X-ray micro-computed tomography (micro-CT). Hydrogels exhibited a linear increase in X-ray attenuation with increased Au NP concentration to enable quantitative imaging by contrast-enhanced micro-CT. The enzymatic and hydrolytic degradation kinetics of gelMA-Au NP hydrogels were longitudinally monitored by micro-CT for up to one month in vitro, yielding results that were consistent with concurrent measurements by optical spectroscopy and gravimetric analysis. Importantly, AuMA NPs did not disrupt the hydrogel network, rheology, mechanical properties, and hydrolytic stability compared with gelMA alone. GelMA-Au NP hydrogels were thus able to be bioprinted into well-defined three-dimensional architectures supporting endothelial cell viability and growth. Overall, AuMA NPs enabled the preparation of both conventional photopolymerized hydrogels and bioprinted scaffolds with tunable X-ray contrast for noninvasive, longitudinal monitoring of placement, degradation, and NP release by micro-CT.

Nondestructive, longitudinal measurement of collagen scaffold degradation using computed tomography and gold nanoparticles.

Biodegradable materials, such as collagen scaffolds, are used extensively in clinical medicine for tissue regeneration and/or as an implantable drug delivery vehicle. However, available methods to study biomaterial degradation are typically invasive, destructive, and/or non-volumetric. Therefore, the objective of this study was to investigate a new method for nondestructive, longitudinal, and volumetric measurement of collagen scaffold degradation. Gold nanoparticles (Au NPs) were covalently conjugated to collagen fibrils during scaffold preparation to enable contrast-enhanced imaging of collagen scaffolds. The X-ray attenuation of as-prepared scaffolds increased linearly with increased Au NP concentration such that ≥60 mM Au NPs provided sufficient contrast to measure scaffold degradation. Collagen scaffold degradation kinetics were measured to increase during in vitro enzymatic degradation in media with an increased concentration of collagenase. The scaffold degradation kinetics measured by micro-CT exhibited lower variability compared with gravimetric measurement and were validated by measurement of the release of Au NPs from the same samples by optical spectroscopy. Thus, Au NPs and CT synergistically enabled nondestructive, longitudinal, and volumetric measurement of collagen scaffold degradation.