Platelet-rich plasma (PRP) treatments have demonstrated clinical benefit for osteoarthritis (OA), although reported outcomes remain inconsistent. Hydrogel-based delivery devices can enhance therapeutic efficacy by prolonging local protein exposure, but effective design depends on characterizing PRP diffusion and the complex protein-protein and protein-matrix interactions that govern release kinetics. Conventional bulk release studies provide limited mechanistic insight into protein transport within complex, physiologically relevant microenvironments, where macromolecular crowding, protein-protein interactions, hydrogel confinement, and patient-specific synovial fluid composition collectively affect release kinetics. To capture this complexity, we used fluorescence correlation spectroscopy (FCS) to directly quantify diffusion coefficients of four representative PRP proteins with varying size and properties across a series of complex environments that represent PRP, the delivery device, and the intended host microenvironment. Diffusivity decreased with increasing protein size, solution viscosity, crowding density, micro-clot formation, and confinement from the hydrogel. Diffusion coefficients obtained via FCS correlated strongly (R = 0.84) with effective diffusivities calculated from bulk release experiments and enabled mathematical modeling of protein release kinetics using Fickian diffusion models from both slab hydrogels and microspheres of varying diameter. Together, this study demonstrated a framework for the utility of FCS in characterizing hindered diffusion within complex, multicomponent biological systems, thereby guiding the rational design of hydrogel-based PRP delivery platforms.

Four-ball tribometers are widely used to characterize the efficacy of lubricants in sliding contact. However, the standard apparatus requires 5 mL or more of fluid, which makes the characterization of biological fluids such as synovial fluid difficult. Here, we present a four-ball tribometer that requires less than a tenth of the sample volume and that is easy to replicate on any rheometer. An upper steel or polystyrene ball was attached to a parallel plate rheology geometry, then lowered onto three lower balls positioned and stabilized using an additively manufactured holder. Rheometer controls were then used to control axial force (contact pressure) and upper ball rotational velocity (sliding speed). The setup was validated on three well-characterized lubricant systems: motor oil, glycerol/water mixtures, and hyaluronic acid. Static and dynamic coefficients of Coulomb friction and wear “scar” test results were reproducible and consistent with trends from the literature. Simulated healthy and diseased synovial fluid was also characterized to demonstrate the setup’s utility in measuring lubrication by small volumes of biological samples. The tribo-rheology setup shows promise for quantifying the lubrication properties of small volumes of precious samples.

Hydrogels are crosslinked polymer networks with a large amount of water; hydrogels can be found naturally, such as collagen and gelatin, or can be made synthetically. The latter are nowadays more in demand due to their higher water absorption capacity and long service life; their tunable properties and versatile fabrication methods have been exploited in a variety of engineering applications, including sensing technologies and drug screening. Because of their similar characteristics to soft biological tissues, hydrogels have also been the focus of research in the biomaterials community and have been studied for their use in biomedical applications such as tissue engineering and regenerative medicine. This Collection on hydrogels highlights some exciting hydrogel developments and applications.

There is renewed interest in three-dimensional bioengineered models that replicate key aspects of the environment for the study of cellular behavior, with one key aspect being cell interactions with matrix interfaces. Here, we developed a dual-stiffness hydrogel-encapsulated glioblastoma (GBM) spheroid model to investigate GBM spreading along a stiffness interface. GBM is an aggressive brain cancer with a patient prognosis of 12-18 months, which is known to spread to distant brain regions by following stiffness interfaces. Our model consisted of a soft, 5% w/v, polyethylene glycol (PEG) hydrogel to mimic the native brain tissue and a stiff, 10% w/v, PEG hydrogel to replicate the stiffer GBM microenvironment. To ensure spheroids fall along the boundary, we adjusted the gelation time of the gel by varying the pH of the gel precursor solution. Encapsulated spheroids were assessed for infiltration and viability for up to 7 days. Spheroids exhibited high viability in all hydrogels. Spheroids showed a higher infiltration index in the soft hydrogel, and migration across the stiffness interface occurred only from the soft to the stiff hydrogel in the dual-stiffness gels. The developed model has a simple, robust design for studying GBM behavior , a high degree of imageability, requires no specialized equipment to prepare, and is compatible with a multiwell plate format for easy handling and analysis.

Self-assembled peptide-based biomaterials provide versatile platforms for biomedical uses, featuring customizable physicochemical properties, biocompatibility, and dynamic capabilities. This self-assembly process is primarily dictated by primary sequence features, such as hydrophobicity, length, and charge, leading to the formation of fibrils and hydrogels. Amphipathic peptides, with alternating polar and hydrophobic residues, are especially effective in forming supramolecular nanofibers stabilized by π-π interactions and hydrogen bonds. Chemical modifications on aromatic side chains are promising for controlling assembly morphology, stability, and biological activity. However, the influence of these substituents on peptide packing and immunogenicity remains relatively unexplored. Herein, we examine the effect of substituents on benzyl groups attached to short amphipathic peptides. By introducing different electron-donating and withdrawing groups at the para-position of benzyl rings and modifying the chain length connecting the backbone to the aromatic moiety, we observe notable effects on fibril formation, molecular packing, and immunogenicity both in vitro and in vivo. Our results show that subtle chemical modifications are practical tools for designing tailored peptide nanomaterials with promising potential in vaccine delivery, tissue engineering, and regenerative medicine.