A prominent obstacle in scaling up tissue engineering technologies for human applications is engineering an adequate supply of oxygen and nutrients throughout artificial tissues. Sugar glass has emerged as a promising 3D-printable, sacrificial material that can be used to embed perfusable networks within cell-laden matrices to improve mass transfer. To characterize and optimize a previously published sugar ink, we investigated the effects of sucrose, glucose, and dextran concentration on the glass transition temperature ( T g ), printability, and stability of 3D-printed sugar glass constructs. We identified a sucrose ink formulation with a significantly higher T g (40.0 ± 0.9°C) than the original formulation (sucrose-glucose blend, T g = 26.2 ± 0.4°C), which demonstrated a pronounced improvement in printability, resistance to bending, and final print stability, all without changing dissolution kinetics and decomposition temperature. This formulation allowed printing of 10-cm-long horizontal cantilever filaments, which can enable the printing of complex vascular segments along the x-, y-, and z-axes without the need for supporting structures. Vascular templates with a single inlet and outlet branching into nine channels were 3D printed using the improved formulation and subsequently used to generate perfusable alginate constructs. The printed lattice showed high fidelity with respect to the input geometry, although with some channel deformation after alginate casting and gelation—likely due to alginate swelling. Compared with avascular controls, no significant acute cytotoxicity was noted when casting pancreatic beta cell-laden alginate constructs around improved ink filaments, whereas a significant decrease in cell viability was observed with the original ink. The improved formulation lends more flexibility to sugar glass 3D printing by facilitating the fabrication of larger, more complex, and more stable sacrificial networks. Rigorous characterization and optimization methods for improving sacrificial inks may facilitate the fabrication of functional cellular constructs for tissue engineering, cellular biology, and other biomedical applications.
Brachytherapy (BT) is a widely used clinical procedure for localized cervical cancer treatment. In addition, gold nanoparticles (AuNPs) have been demonstrated as powerful radiosensitizers in BT procedures. Prior to irradiation by a BT device, their delivery to tumors can enhance the radiation effect by generating low‐energy photons and electrons, leading to reactive oxygen species (ROS) production, lethal to cells. No efficient delivery system has been proposed until now for AuNP topical delivery to localized cervical cancer in the context of BT. This article reports an original approach developed to accelerate the preclinical studies of AuNP‐enhanced BT procedures. First, an AuNP‐containing hydrogel (Pluronic F127, alginate) is developed and tested in mice for degradation, AuNP release, and biocompatibility. Then, custom‐made 3D‐printed radioactive BT inserts covered with a AuNP‐containing hydrogel cushion are designed and administered by surgery in mice (HeLa xenografts), which allows for measuring AuNP penetration in tumors (≈100 µm), co‐registered with the presence of ROS produced through the interactions of radiation and AuNPs. Biocompatible AuNPs‐releasing hydrogels could be used in the treatment of cervical cancer prior to BT, with impact on the total amount of radiation needed per BT treatment, which will result in benefits to the preservation of healthy tissues surrounding cancer.
Hydrogels are widely used as cell scaffolds in several biomedical applications. Once implanted in vivo, cell scaffolds must often be visualized, and monitored overtime. However, cell scaffolds appear poorly contrasted in most biomedical imaging modalities such as magnetic resonance imaging (MRI). MRI is the imaging technique of choice for high‐resolution visualization of low‐density, water‐rich tissues. Attempts to enhance hydrogel contrast in MRI are performed with “negative” contrast agents that produce several image artifacts impeding the delineation of the implant's contours. In this study, a magnetic ink based on ultra‐small iron oxide nanoparticles (USPIONs; <5 nm diameter cores) is developed and integrated into biocompatible alginate hydrogel used in cell scaffolding applications. Relaxometric properties of the magnetic hydrogel are measured, as well as biocompatibility and MR‐visibility (T1‐weighted mode; in vitro and in vivo). A 2‐week MR follow‐up study is performed in the mouse model, demonstrating no image artifacts, and the retention of “positive” contrast overtime, which allows very precise delineation of tissue grafts with MRI. Finally, a 3D‐contouring procedure developed to facilitate graft delineation and geometrical conformity assessment is applied on an inverted template alginate pore network. This proof‐of‐concept establishes the possibility to reveal precisely engineered hydrogel structures using this USPIONs ink high‐visibility approach.
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