Chondroitin Sulfate/Hyaluronic Acid-Blended Hydrogels Suppress Chondrocyte Inflammation under Pro-Inflammatory Conditions.

Osteoarthritis is characterized by enzymatic breakdown of the articular cartilage via the disruption of chondrocyte homeostasis, ultimately resulting in the destruction of the articular surface. Decades of research have highlighted the importance of inflammation in osteoarthritis progression, with inflammatory cytokines shifting resident chondrocytes into a pro-catabolic state. Inflammation can result in poor outcomes for cells implanted for cartilage regeneration. Therefore, a method to promote the growth of new cartilage and protect the implanted cells from the pro-inflammatory cytokines found in the joint space is required. In this study, we fabricate two gel types: polymer network hydrogels composed of chondroitin sulfate and hyaluronic acid, glycosaminoglycans (GAGs) known for their anti-inflammatory and prochondrogenic activity, and interpenetrating networks of GAGs and collagen I. Compared to a collagen-only hydrogel, which does not provide an anti-inflammatory stimulus, chondrocytes in GAG hydrogels result in reduced production of pro-inflammatory cytokines and enzymes as well as preservation of collagen II and aggrecan expression. Overall, GAG-based hydrogels have the potential to promote cartilage regeneration under pro-inflammatory conditions. Further, the data have implications for the use of GAGs to generally support tissue engineering in pro-inflammatory environments.

Redox-Responsive Hydrogels with Decoupled Initial Stiffness and Degradation.

Disulfide-cross-linked hydrogels have been widely used for biological applications because of their degradability in response to redox stimuli. However, degradability often depends on polymer concentration, which also influences the hydrogel mechanical properties such as the initial stiffness. Here, we describe a one-pot cross-linking approach utilizing both a thiol-ene reaction through a Michael pathway with divinyl sulfone (DVS) to form non-reducible thioether bonds and thiol oxidation promoted by ferric ethylenediaminetetraacetic acid (Fe-EDTA) to form reducible disulfide bonds. The ratio between these two bonds was modulated by varying the DVS concentration used, and the initial shear or elastic modulus and degradation rate of the hydrogels were decoupled. These gels had tunable release rates of encapsulated dextran when exposed to 10 µM glutathione. Fibroblast encapsulation results suggested good cytocompatibility of the cross-linking reactions. This work shows the potential of combining DVS and Fe-EDTA to create thiol-cross-linked hydrogels as redox-responsive drug delivery vehicles and tissue engineering scaffolds with variable degradability.

Collagen- and hyaluronic acid-based hydrogels and their biomedical applications.

Hydrogels have been widely investigated in biomedical fields due to their similar physical and biochemical properties to the extracellular matrix (ECM). Collagen and hyaluronic acid (HA) are the main components of the ECM in many tissues. As a result, hydrogels prepared from collagen and HA hold inherent advantages in mimicking the structure and function of the native ECM. Numerous studies have focused on the development of collagen and HA hydrogels and their biomedical applications. In this extensive review, we provide a summary and analysis of the sources, features, and modifications of collagen and HA. Specifically, we highlight the fabrication, properties, and potential biomedical applications as well as promising commercialization of hydrogels based on these two natural polymers.

Collagen Type I and II Blend Hydrogel with Autologous Mesenchymal Stem Cells as a Scaffold for Articular Cartilage Defect Repair.

Collagen type II is a promising material to repair cartilage defects since it is a major component of articular cartilage and plays a key role in chondrocyte function. This study investigated the chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs) embedded within a 3:1 collagen type I to II blend (Col I/II) hydrogel or an all collagen type I (Col I) hydrogel. Glycosaminoglycan (GAG) production in Col I/II hydrogels was statistically higher than that in Col I hydrogels or pellet culture, and these results suggested that adding collagen type II promoted GAG production. Col I/II hydrogels had statistically lower alkaline phosphatase (AP) activity than pellets cultured in a chondrogenic medium. The ability of MSCs encapsulated in Col I/II hydrogels to repair cartilage defects was investigated by creating two cartilage defects in the femurs of rabbits. After 13 weeks, histochemical staining suggested that Col I/II blend hydrogels provided favorable conditions for cartilage repair. Histological scoring revealed a statistically higher cartilage repair score for the Col I/II hydrogels compared to either the Col I hydrogels or empty defect controls. Results from this study suggest that there is clinical value in the cartilage repair capabilities of our Col I/II hydrogel with encapsulated MSCs.