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Bioprinting is an additive manufacturing technique that combines living cells, biomaterials, and biological molecules to develop biologically functional constructs. Three-dimensional (3D) bioprinting is commonly used as anin vitromodeling system and is a more accurate representation ofin vivoconditions in comparison to two-dimensional cell culture. Although 3D bioprinting has been utilized in various tissue engineering and clinical applications, it only takes into consideration the initial state of the printed scaffold or object. Four-dimensional (4D) bioprinting has emerged in recent years to incorporate the additional dimension of time within the printed 3D scaffolds. During the 4D bioprinting process, an external stimulus is exposed to the printed construct, which ultimately changes its shape or functionality. By studying how the structures and the embedded cells respond to various stimuli, researchers can gain a deeper understanding of the functionality of native tissues. This review paper will focus on the biomaterial breakthroughs in the newly advancing field of 4D bioprinting and their applications in tissue engineering and regeneration. In addition, the use of smart biomaterials and 4D printing mechanisms for tissue engineering applications is discussed to demonstrate potential insights for novel 4D bioprinting applications. To address the current challenges with this technology, we will conclude with future perspectives involving the incorporation of biological scaffolds and self-assembling nanomaterials in bioprinted tissue constructs.

 

Microneedles have recently emerged as a powerful tool for minimally invasive drug delivery and body fluid sampling. To date, high‐resolution fabrication of microneedle arrays (MNAs) is mostly achieved by the utilization of sophisticated facilities and expertise. Particularly, hollow microneedles have usually been manufactured in cleanrooms out of silicon, resin, or metallic materials. Such strategies do not support the fabrication of microneedles from biocompatible/biodegradable materials and limit the capability of multimodal drug delivery for the controlled release of different therapeutics through a combination of injection and sustained diffusion. This study implements low‐cost 3D printers to fabricate relatively large needle arrays, followed by repeatable shrink‐molding of hydrogels to form high‐resolution molds for solid and hollow MNAs with controllable sizes. The developed strategy further enables modulating surface topography of MNAs to tailor their surface area and instantaneous wettability for controllable drug delivery and body fluid sampling. Hybrid gelatin methacryloyl (GelMA)/polyethylene glycol diacrylate (PEGDA) MNAs are fabricated using the developed strategy that can easily penetrate the skin and enable multimodal drug delivery. The proposed method holds promise for affordable, controllable, and scalable fabrication of MNAs by researchers and clinicians for controlled spatiotemporal administration of therapeutics and sample collection.

 

The blood-brain barrier (BBB) is a crucial part of brain anatomy as it is a specialized, protective barrier that ensures proper nutrient transport to the brain, ultimately leading to regulating proper brain function. However, it presents a major challenge in delivering pharmaceuticals to treat central nervous system (CNS) diseases due to this selectivity. A variety of different vehicles have been designed to deliver drugs across this barrier to treat neurodegenerative diseases, greatly impacting the patient’s quality of life. The two main types of vehicles used to cross the BBB are polymers and liposomes, which both encapsulate pharmaceuticals to allow them to transcytose the cells of the BBB. For Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and glioblastoma brain cancer, there are a variety of different nanoparticle treatments in development that increase the bioavailability and targeting ability of existing drugs or new drug targets to decrease symptoms of these diseases. Through these systems, nanomedicine offers a new way to target specific tissues, especially for the CNS, and treat diseases without the systemic toxicity that often comes with medications used currently. 

Tissue chip technology has revolutionized biomedical applications and the medical science field for the past few decades. Currently, tissue chips are one of the most powerful research tools aiding in in vitro work to accurately predict the outcome of studies when compared to monolayer two-dimensional (2D) cell cultures. While 2D cell cultures held prominence for a long time, their lack of biomimicry has resulted in a transition to 3D cell cultures, including tissue chips technology, to overcome the discrepancies often seen in in vitro studies. Due to their wide range of applications, different organ systems have been studied over the years, one of which is the blood brain barrier (BBB) which is discussed in this review. The BBB is an incredible protective unit of the body, keeping out pathogens from entering the brain through vasculature. However, there are some microbes and certain diseases that disrupt the function of this barrier which can lead to detrimental outcomes. Over the past few years, various designs of the BBB have been proposed and modeled to study drug delivery and disease modeling on Earth. More recently, researchers have started to utilize tissue chips in space to study the effects of microgravity on human health. BBB tissue chips in space can be a tool to understand function mechanisms and therapeutics. This review addresses the limitations of monolayer cell culture which could be overcome with utilizing tissue chips technology. Current BBB models on Earth and how they are fabricated as well as what influences the BBB cell culture in tissue chips are discussed. Then, this article reviews how application of these technologies together with incorporating biosensors in space would be beneficial to help in predicting a more accurate physiological response in specific tissue or organ chips. Finally, the current platforms used in space and some solutions to overcome some shortcomings for future BBB tissue chip research are also discussed. 

Ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, have had a profound impact on millions of patients. In the past couple of decades, these diseases have been treated using conventional techniques but have also presented certain challenges and limitations that affect patient experience and outcomes. To address this, biomaterials have been used for ocular drug delivery, and a wide range of systems have been developed. This review will discuss some of the major classes and examples of biomaterials used for the treatment of prominent ocular diseases, including ocular implants (biodegradable and non-biodegradable), nanocarriers (hydrogels, liposomes, nanomicelles, DNA-inspired nanoparticles, and dendrimers), microneedles, and drug-loaded contact lenses. We will also discuss the advantages of these biomaterials over conventional approaches with support from the results of clinical trials that demonstrate their efficacy. 

Research interest in nanoscale biomaterials has continued to grow in the past few decades, driving the need to form families of nanomaterials grouped by similar physical or chemical properties. Nanotubes have occupied a unique space in this field, primarily due to their high versatility in a wide range of biomedical applications. Although similar in morphology, members of this nanomaterial family widely differ in synthesis methods, mechanical and physiochemical properties, and therapeutic applications. As this field continues to develop, it is important to provide insight into novel biomaterial developments and their overall impact on current technology and therapeutics. In this review, we aim to characterize and compare two members of the nanotube family: carbon nanotubes (CNTs) and janus-base nanotubes (JBNts). While CNTs have been extensively studied for decades, JBNts provide a fresh perspective on many therapeutic modalities bound by the limitations of carbon-based nanomaterials. Herein, we characterize the morphology, synthesis, and applications of CNTs and JBNts to provide a comprehensive comparison between these nanomaterial technologies.