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Abstract Hydrogels are widely used in tissue engineering but conventional homogeneous polymerization often creates dense matrices that hinder cell migration and restrict extracellular matrix production. The motivation of this project was to overcome these limitations by developing a heterogeneously crosslinkable hydrogel platform that enables both cell migration and matrix deposition. We present a two-step heterogeneous polymerization approach that introduces spatial variations in matrix density, producing tunable, cell-sized pores that promote migration, proliferation, and matrix synthesis. As an implementation, gelatin was pre-assembled into microribbon-like building blocks using a Dynamic Molding process, methacrylated to introduce crosslinkable groups, chemically modified, washed, and freeze-dried. Upon rehydration, the ribbons formed a moldable paste that could be mixed with cells and photo-crosslinked into scaffolds with in situ–formed, cell-sized pores. The main novelty of this method is the introduction of chemical modifications with methacrylic anhydride (MAA), acetic anhydride (AceA), and succinic anhydride (SucA), which enable a controlled two-step heterogeneous polymerization and allow independent tuning of scaffold microstructure, mechanics, and degradation. AceA reduced crosslink density and accelerated degradation, whereas SucA promoted swelling, enhanced mechanical strength, and slowed degradation. Cell studies revealed that SucA-modified scaffolds supported superior adhesion and proliferation compared to AceA-modified and unmodified controls. Such work may significantly impact the design of next-generation scaffolds by providing a versatile platform that integrates structural, mechanical, and biochemical control for regenerative medicine applications. 

Abstract The gold standard to measure arterial health is vasodilation in response to nitric oxide. Vasodilation is generally measured via pressure myography of arteries isolated from animal models. However, animal arteries can be difficult to obtain and may have limited relevance to human physiology. It is, therefore, critical to engineer human cell-based arterial models capable of contraction. Vascular smooth muscle cells (SMCs) must be circumferentially aligned around the vessel lumen to contract the vessel, which is challenging to achieve in a soft blood vessel model. In this study, we used gelatin microribbons to circumferentially align SMCs inside a hydrogel channel. To accomplish this, we created tunable gelatin microribbons of varying stiffnesses and thicknesses and assessed how SMCs aligned along them. We then wrapped soft, thick microribbons around a needle and encapsulated them in a gelatin methacryloyl hydrogel, forming a microribbon-lined channel. Finally, we seeded SMCs inside the channel and showed that they adhered best to fibronectin and circumferentially aligned in response to the microribbons. Together, these data show that tunable gelatin microribbons can be used to circumferentially align SMCs inside a channel. This technique can be used to create a human artery-on-a-chip to assess vasodilation via pressure myography, as well as to align other cell types for 3Din vitromodels. 

ObjectiveTo elucidate the role of decorin, a small leucine‐rich proteoglycan, in the degradation of cartilage matrix during the progression of post‐traumatic osteoarthritis (OA). MethodsThree‐month–old decorin‐null (Dcn^−/−) and inducible decorin‐knockout (Dcn^iKO) mice were subjected to surgical destabilization of the medial meniscus (DMM) to induce post‐traumaticOA. TheOAphenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy–nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro–computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild‐type and Dcn^−/−mice were stimulated with the inflammatory cytokine interleukin‐1β (IL‐1β) in vitro (n = 6 mice per group). The resulting chondrocyte response toIL‐1β and release ofsGAGs were quantified. ResultsIn both Dcn^−/−and Dcn^iKOmice, the absence of decorin resulted in acceleratedsGAGloss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P< 0.05). Also, Dcn^−/−mice developed more salient osteophytes, illustrating more severeOA. In cartilage explants treated withIL‐1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion ofsGAGs was released to the media from Dcn^−/−mouse explants, in both live and devitalized conditions (P< 0.05). ConclusionIn post‐traumaticOA, decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.