Three-dimensional (3D) bioprinting is on the cusp of permitting the direct fabrication of artificial living tissue. Multicellular building blocks (bioinks) are dispensed layer by layer and scaled for the target construct. However, only a few materials are able to fulfill the considerable requirements for suitable bioink formulation, a critical component of efficient 3D bioprinting. Alginate, a naturally occurring polysaccharide, is clearly the most commonly employed material in current bioinks. Here, we discuss the benefits and disadvantages of the use of alginate in 3D bioprinting by summarizing the most recent studies that used alginate for printing vascular tissue, bone and cartilage. In addition, other breakthroughs in the use of alginate in bioprinting are discussed, including strategies to improve its structural and degradation characteristics. In this review, we organize the available literature in order to inspire and accelerate novel alginate-based bioink formulations with enhanced properties for future applications in basic research, drug screening and regenerative medicine.

The number of biomedical applications of hydrogels is increasing rapidly on account of their unique physical, structural, and mechanical properties. The utility of hydrogels as drug delivery systems or tissue engineering scaffolds critically depends on the control of diffusion of solutes through the hydrogel matrix. Predicting or even modeling this diffusion is challenging due to the complex structure of hydrogels. Currently, the diffusivity of solutes in hydrogels is typically modeled by one of three main theories proceeding from distinct diffusion mechanisms: (i) hydrodynamic, (ii) free volume, and (iii) obstruction theory. Yet, a comprehensive predictive model is lacking. Thus, time and capital-intensive trial-and-error procedures are used to test the viability of hydrogel applications. In this work, we have developed a model for the diffusivity of solutes in hydrogels combining the three main theoretical frameworks, which we call the multiscale diffusion model (MSDM). We verified the MSDM by analyzing the diffusivity of dextran of different sizes in a series of poly(ethylene glycol) (PEG) hydrogels with distinct mesh sizes. We measured the subnanoscopic free volume by positron annihilation lifetime spectroscopy (PALS) to characterize the physical hierarchy of these materials. In addition, we performed a meta-analysis of literature data from previous studies on the diffusion of solutes in hydrogels. The model presented outperforms traditional models in predicting solute diffusivity in hydrogels and provides a practical approach to predicting the transport properties of solutes such as drugs through hydrogels used in many biomedical applications.

Vaccines aim to elicit a robust, yet targeted, immune response. Failure of a vaccine to elicit such a response arises in part from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system’s natural response to extended pathogen exposure during infection by designing an easily administered slow-delivery vaccine platform. We utilized an injectable and self-healing polymer–nanoparticle (PNP) hydrogel platform to prolong the codelivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique delivery characteristics, whereby physicochemically distinct compounds (such as antigen and adjuvant) could be codelivered over the course of weeks. When administered in mice, hydrogel-based sustained vaccine exposure enhanced the magnitude, duration, and quality of the humoral immune response compared to standard PBS bolus administration of the same model vaccine. We report that the creation of a local inflammatory niche within the hydrogel, coupled with sustained exposure of vaccine cargo, enhanced the magnitude and duration of germinal center responses in the lymph nodes. This strengthened germinal center response promoted greater antibody affinity maturation, resulting in a more than 1000-fold increase in antigen-specific antibody affinity in comparison to bolus immunization. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of subunit vaccines.

Many biomaterials have been developed which aim to match the elastic modulus of the brain for improved interfacing. However, other properties such as ultimate toughness, tensile strength, poroviscoelastic responses, energy dissipation, conductivity, and mass diffusivity also need to be considered.

Positron annihilation lifetime spectroscopy (PALS) provides a direct measurement of the free volume void sizes in polymers and biological systems. This free volume is critical in explaining and understanding physical and mechanical properties of polymers. Moreover, PALS has been recently proposed as a potential tool in detecting cancer at early stages, probing the differences in the subnanometer scale free volume voids between cancerous/healthy skin samples of the same patient. Despite several investigations on free volume in complex cancerous tissues, no positron annihilation studies of living cancer cell cultures have been reported. We demonstrate that PALS can be applied to the study in human living 3D cell cultures. The technique is also capable to detect atomic scale changes in the size of the free volume voids due to the biological responses to TGF-β. PALS may be developed to characterize the effect of different culture conditions in the free volume voids of cells grown in vitro.