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

Abstract

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.

3D bioprinting of nanoparticle-laden hydrogel scaffolds with enhanced antibacterial and imaging properties

“…A 0.5% (w/v) concentration of lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) was used as a photoinitiator to crosslink the bioinks under a 10 mW/cm 2 UV light source for 2 min. These crosslinking parameters were chosen based on our previous experiences ( Li et al., 2022 ; ML Tomov et al., 2019 ; Ning et al., 2020 ; Ning et al., 2022 ; Ning et al., 2021 ) to generate GelMA constructs at biologically relevant stiffness (mimicking soft tissue stiffness, ∼20–140 kPa ( Huang et al., 2012 ; Serpooshan et al., 2013 ; Wei et al., 2015 )). 3D printed constructs were designed using Autodesk Fusion 360 CAD software (Autodesk Inc., San Rafael, CA) and converted to the standard STL file format for printing.…”

Targeted Rapamycin Delivery via Magnetic Nanoparticles to Address Stenosis in a 3D Bioprinted in Vitro Model of Pulmonary Veins

“…GelMA-based bioink solution (CytoInk6000) [27][28][29] was custom-designed and prepared for DLP bioprinting to yield adequate fidelity. [30][31][32][33] Briefly, 10% (w/v) of porcine GelMA (Sigma) was mixed with cold water fish gelatin (10% w/v) (Sigma), PEGDA6000 (2.5% w/v) (Sigma), LAP photoinitiator (1% w/v), and 1X pen/strep to inhibit contamination. Mixed reagents were suspended in sterile PBS and incubated overnight at 37 °C while protected from light.…”