Recent advances in the field of bioprinting have led to the development of perfusable complex structures. However, most of the existing printed vascular channels lack the composition or key structural and physiological features of natural blood vessels or they make use of more easily printable but less biocompatible hydrogels. Here, we use a drop-on-demand bioprinting technique to generate in vitro blood vessel models, consisting of a continuous endothelium imitating the tunica intima, an elastic smooth muscle cell layer mimicking the tunica media, and a surrounding fibrous and collagenous matrix of fibroblasts mimicking the tunica adventitia. These vessel models with a wall thickness of up to 425 µm and a diameter of about 1 mm were dynamically cultivated in fluidic bioreactors for up to three weeks under physiological flow conditions. High cell viability (>83%) after printing and the expression of VE-Cadherin, smooth muscle actin, and collagen IV were observed throughout the cultivation period. It can be concluded that the proposed novel technique is suitable to achieve perfusable vessel models with a biofunctional multilayer wall composition. Such structures hold potential for the creation of more physiologically relevant in vitro disease models suitable especially as platforms for the pre-screening of drugs.
In the past decade, anisometric rod‐shaped microgels have attracted growing interest in the materials‐design and tissue‐engineering communities. Rod‐shaped microgels exhibit outstanding potential as versatile building blocks for 3D hydrogels, where they introduce macroscopic anisometry, porosity, or functionality for structural guidance in biomaterials. Various fabrication methods have been established to produce such shape‐controlled elements. However, continuous high‐throughput production of rod‐shaped microgels with simultaneous control over stiffness, size, and aspect ratio still presents a major challenge. A novel microfluidic setup is presented for the continuous production of rod‐shaped microgels from microfluidic plug flow and jets. This system overcomes the current limitations of established production methods for rod‐shaped microgels. Here, an on‐chip gelation setup enables fabrication of soft microgel rods with high aspect ratios, tunable stiffness, and diameters significantly smaller than the channel diameter. This is realized by exposing jets of a microgel precursor to a high intensity light source, operated at specific pulse sequences and frequencies to induce ultra‐fast photopolymerization, while a change in flow rates or pulse duration enables variation of the aspect ratio. The microgels can assemble into 3D structures and function as support for cell culture and tissue engineering.
Microbubbles (MB) are routinely used ultrasound (US) contrast agents that have recently attracted increasing attention as stimuli-responsive drug delivery systems. In order to better understand MB-based drug delivery, we studied the role of drug hydrophobicity and molecular weight on MB loading, shelf-life stability, US properties and drug release. Eight model drugs, varying in hydrophobicity and molecular weight, were loaded into the shell of poly(butyl cyanoacrylate) (PBCA) MB. In the case of drugs with progesterone as a common structural backbone (i.e. for corticosteroids), loading capacity and drug release correlated well with hydrophobicity and molecular weight. Conversely, when employing drugs with no structural similarity (i.e. four different fluorescent dyes), loading capacity and release did not correlate with hydrophobicity and molecular weight. All model drug-loaded MB formulations could be equally efficiently destroyed upon exposure to US. Together, these findings provide valuable insights on how the physicochemical properties of (model) drug molecules affect their loading and retention in and US-induced release from polymeric MB, thereby facilitating the development of drug-loaded MB formulations for US-triggered drug delivery.
Human induced pluripotent stem cells (hiPSCs) are used as an alternative for human embryonic stem cells. Cardiomyocytes derived from hiPSCs are employed in cardiac tissue regeneration constructs due to the heart's low regeneration capacity after infarction. A coculture of hiPSC-CM and primary dermal fibroblasts is encapsulated in injectable poly(ethylene glycol)-based microgels via microfluidics to enhance the efficiency of regenerative cell transplantations. The microgels are prepared via Michael-type addition of multi-arm PEG-based molecules with an enzymatically degradable peptide as a crosslinker and modified with a cell-adhesive peptide. Cell−cell interactions and, consequently, cell viability are improved by a thin extracellular matrix (ECM) coating formed on the cell surfaces via layer-by-layer (LbL) deposition. The beating strength of encapsulated cardiomyocytes (∼60 BPM) increases by 2-fold compared to noncoated cells. The combination of microfluidics with the LbL technique offers a new technology to fabricate functional cardiac mini tissues for cell transplantation therapies.
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