Osteoarthritis (OA) is a degenerative disease that affects various tissues surrounding joints such as articular cartilage, subchondral bone, synovial membrane, and ligaments. No therapy is currently available to completely prevent the initiation or progression of the disease partly due to poor understanding of the mechanisms of the disease pathology. Cartilage is the main tissue afflicted by OA, and chondrocytes, the sole cellular component in the tissue, actively participate in the degeneration process. Multiple factors affect the development and progression of OA including inflammation that is sustained during the progression of the disease and alteration in biomechanical conditions due to wear and tear or trauma in cartilage. During the progression of OA, extracellular matrix (ECM) of cartilage is actively remodeled by chondrocytes under inflammatory conditions. This alteration of ECM, in turn, changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. The changes in ECM composition and structure also prevent participation of mesenchymal stem cells in the repair process by inhibiting their chondrogenic differentiation. This review focuses on how inflammation-induced ECM remodeling disturbs cellular activities to prevent self-regeneration of cartilage in the pathology of OA.
Small pore sizes inherent to electrospun matrices can hinder efficient cellular ingrowth. To facilitate infiltration while retaining its extracellular matrix-like character, electrospinning was combined with salt leaching to produce a scaffold having deliberate, engineered delaminations. We made elegant use of a specific randomizing component of the electrospinning process, the Taylor Cone and the falling fiber beneath it, to produce a uniform, well-spread distribution of salt particles. After 3 weeks of culture, up to 4 mm of cellular infiltration was observed, along with cellular coverage of up to 70% within the delaminations. To our knowledge, this represents the first observation of extensive cellular infiltration of electrospun matrices. Infiltration appears to be driven primarily by localized proliferation rather than coordinated cellular locomotion. Cells also moved from the salt-generated porosity into the surrounding electrospun fiber matrix. Given that the details of salt deposition (amount, size, and number density) are far from optimized, the result provides a convincing illustration of the ability of mammalian cells to interact with appropriately tailored electrospun matrices. These layered structures can be precisely fabricated by varying the deposition interval and particle size conceivably to produce in vivo-like gradients in porosity such that the resulting scaffolds better resemble the desired final structure.
14 January 2016 in Journal of Materials Chemistry A