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Scaffolds derived from cartilage extracellular matrix may contain intrinsic chondroinductivity and have promise for cartilage regeneration. Cartilage is typically ground into devitalized particles (DVC) and several groups have pioneered innovative methods to rebuild the DVC into a new scaffold. However, challenges remain regarding the fluid and solid biomechanics of cartilage-based scaffolds in achieving 1) high mechanical performance akin to native cartilage and 2) easy surgical delivery/retention. Fortunately, photocrosslinking bioinks may benefit clinical translation: paste-like/injectable precursor rheology facilitates surgical placement, and in situ photocrosslinking enables material retention within any size/shape of defect. While solubilized DVC has been modified with methacryloyls (MeSDVC), MeSDVC is limited by slow crosslinking times (e.g., 5-10 min). Therefore, in the current study, we fabricated a pentenoate-modified SDVC (PSDVC), to enable a faster crosslinking reaction via a thiol-ene click chemistry. The crosslinking time of the PSDVC was faster (∼1.7 min) than MeSDVC (∼4 min). We characterized the solid and fluid mechanics/printabilities of PSDVC, pentenoate-modified hyaluronic acid (PHA), and the PHA or PSDVC with added DVC particles. While the addition of DVC particles enhanced the printed shape fidelity of PHA or PSDVC, the increased clogging decreased the ease of printing and cell viability after bioprinting, and future refinement is needed for DVC-containing bioinks. However, the PSDVC alone had a paste-like rheology/good bioprintability prior to crosslinking, the fastest crosslinking time (i.e., 1.7 min), and the highest compressive modulus (i.e., 3.12 ± 0.41 MPa) after crosslinking. Overall, the PSDVC may have future potential as a translational material for cartilage repair., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Interactions between lung epithelium and interstitial fibroblasts are increasingly recognized as playing a major role in the progression of several lung pathologies, including cancer. Three-dimensional in vitro co-culture systems offer tissue-relevant platforms to study the signaling interplay between diseased and healthy cell types. Such systems provide a controlled environment in which to probe the mechanisms involved in epithelial-mesenchymal crosstalk. To recapitulate the native alveolar tissue architecture, we employed a cyst templating technique to culture alveolar epithelial cells on photodegradable microspheres and subsequently encapsulated the cell-laden spheres within poly (ethylene glycol) (PEG) hydrogels containing dispersed pulmonary fibroblasts. A fibroblast cell line (CCL-210) was co-cultured with either healthy mouse alveolar epithelial primary cells or a cancerous alveolar epithelial cell line (A549) to probe the influence of tumor-stromal interactions on proliferation, migration, and matrix remodeling. In 3D co-culture, cancerous epithelial cells and fibroblasts had higher proliferation rates. When examining fibroblast motility, the fibroblasts migrated faster when co-cultured with cancerous A549 cells. Finally, a fluorescent peptide reporter for matrix metalloproteinase (MMP) activity revealed increased MMP activity when A549s and fibroblasts were co-cultured. When MMP activity was inhibited or when cells were cultured in gels with a non-degradable crosslinker, fibroblast migration was dramatically suppressed, and the increase in cancer cell proliferation in co-culture was abrogated. Together, this evidence supports the idea that there is an exchange between the alveolar epithelium and surrounding fibroblasts during cancer progression that depends on MMP activity and points to potential signaling routes that merit further investigation to determine targets for cancer treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)