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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. 

Abstract The incorporation of a secondary network into traditional single‐network hydrogels can enhance mechanical properties, such as toughness and loading to failure. These features are important for many applications, including as biomedical materials; however, the processing of interpenetrating polymer network (IPN) hydrogels is often limited by their multistep fabrication procedures. Here, a one‐pot scheme for the synthesis of biopolymer IPN hydrogels mediated by the simultaneous crosslinking of two independent networks with light, namely: i) free‐radical crosslinking of methacrylate‐modified hyaluronic acid (HA) to form the primary network and ii) thiol–ene crosslinking of norbornene‐modified HA with thiolated guest–host assemblies of adamantane and β‐cyclodextrin to form the secondary network, is reported. The mechanical properties of the IPN hydrogels are tuned by changing the network composition, with high water content (≈94%) hydrogels exhibiting excellent work of fracture, tensile strength, and low hysteresis. As proof‐of‐concept, the IPN hydrogels are implemented as low‐viscosity Digital Light Processing resins to fabricate complex structures that recover shape upon loading, as well as in microfluidic devices to form deformable microparticles. Further, the IPNs are cytocompatible with cell adhesion dependent on the inclusion of adhesive peptides. Overall, the enhanced processing of these IPN hydrogels will expand their utility across applications. 

Abstract Hydrogels are engineered with biochemical and biophysical signals to recreate aspects of the native microenvironment and to control cellular functions such as differentiation and matrix deposition. This deposited matrix accumulates within the pericellular space and likely affects the interactions between encapsulated cells and the engineered hydrogel; however, there has been little work to study the spatiotemporal evolution of matrix at this interface. To address this, metabolic labeling is employed to visualize the temporal and spatial positioning of nascent proteins and proteoglycans deposited by chondrocytes. Within covalently crosslinked hyaluronic acid hydrogels, chondrocytes deposit nascent proteins and proteoglycans in the pericellular space within 1 d after encapsulation. The accumulation of this matrix, as measured by an increase in matrix thickness during culture, depends on the initial hydrogel crosslink density with decreased thicknesses for more crosslinked hydrogels. Encapsulated fluorescent beads are used to monitor the hydrogel location and indicate that the emerging nascent matrix physically displaces the hydrogel from the cell membrane with extended culture. These findings suggest that secreted matrix increasingly masks the presentation of engineered hydrogel cues and may have implications for the design of hydrogels in tissue engineering and regenerative medicine.