Three dimensional (bio)printing of blood vessels: from vascularized tissues to functional arteries.

Tissue engineering has emerged as a strategy for producing functional tissues and organs to treat diseases and injuries. Many chronic conditions directly or indirectly affect normal blood vessel functioning, necessary for material exchange and transport through the body and within tissue-engineered constructs. The interest in vascular tissue engineering is due to two reasons: (1) functional grafts can be used to replace diseased blood vessels, and (2) engineering effective vasculature within other engineered tissues enables connection with the host's circulatory system, supporting their survival. Among various practices, (bio)printing has emerged as a powerful tool to engineer biomimetic constructs. This has been made possible with precise control of cell deposition and matrix environment along with the advancements in biomaterials. (Bio)printing has been used for both engineering stand-alone vascular grafts as well as vasculature within engineered tissues for regenerative applications. In this review article, we discuss various conditions associated with blood vessels, the need for artificial blood vessels, the anatomy and physiology of different blood vessels, available 3D (bio)printing techniques to fabricate tissue-engineered vascular grafts and vasculature in scaffolds, and the comparison among the different techniques. We conclude our review with a brief discussion about future opportunities in the area of blood vessel tissue engineering.

Approximating scaffold printability utilizing computational methods.

Bioprinting facilitates the generation of complex, three-dimensional (3D), cell-based constructs for various applications. Although multiple bioprinting technologies have been developed, extrusion-based systems have become the dominant technology due to the diversity of materials (bioinks) that can be utilized, either individually or in combination. However, each bioink has unique material properties and extrusion characteristics that affect bioprinting utility, accuracy, and precision. Here, we have extended our previous work to achieve high precision (i.e. repeatability) and printability across samples by optimizing bioink-specific printing parameters. Specifically, we hypothesized that a fuzzy inference system (FIS) could be used as a computational method to address the imprecision in 3D bioprinting test data and uncover the optimal printing parameters for a specific bioink that result in high accuracy and precision. To test this hypothesis, we have implemented a FIS model consisting of four inputs (bioink concentration, printing flow rate, speed, and temperature) and two outputs to quantify the precision (scaffold bioprinted linewidth variance) and printability. We validate our use of the bioprinting precision index with both standard and normalized printability factors. Finally, we utilize optimized printing parameters to bioprint scaffolds containing up to 30 × 106cells ml-1with high printability and precision. In total, our results indicate that computational methods are a cost-efficient measure to improve the precision and robustness of extrusion 3D bioprinting.

The infinite possibilities of RNA therapeutics.

Although the study of ribonucleic acid (RNA) therapeutics started decades ago, for many years, this field of research was overshadowed by the growing interest in DNA-based therapies. Nowadays, the role of several types of RNA in cell regulation processes and the development of various diseases have been elucidated, and research in RNA therapeutics is back with force. This short literature review aims to present general aspects of many of the molecules currently used in RNA therapeutics, including in vitro transcribed mRNA (IVT mRNA), antisense oligonucleotides (ASOs), aptamers, small interfering RNAs (siRNAs), and microRNAs (miRNAs). In addition, we describe the state of the art of technologies applied for synthetic RNA manufacture and delivery. Likewise, we detail the RNA-based therapies approved by the FDA so far, as well as the ongoing clinical investigations. As a final point, we highlight the current and potential advantages of working on RNA-based therapeutics and how these could lead to a new era of accessible and personalized healthcare.