Search

Collagen (Col) is commonly used as a natural biomaterial for biomedical applications. Although Col I is the most prevalent col type employed, many collagen types work together in vivo to confer function and biological activity. Thus, blending collagen types can better recapitulate many native environments. This work investigates how hydrogel properties can be tuned through blending collagen types (col I/II and col I/III) and by varying polymerization temperatures. Col I/II results in poorly developed fibril networks, which softened the gels, especially at lower polymerization temperatures. Conversely, col I/III hydrogels exhibit well-connected fibril networks with localized areas of fine fibrils and result in stiffer hydrogels. A decreased molecular mass recovery rate is observed in blended hydrogels. The altered fibril morphologies, mechanical properties, and biological signals of the blended gels can be leveraged to alter cell responses and can be used as models for different tissue types (e.g., healthy vs fibrotic tissue). Furthermore, the biomimetic hydrogel properties are a tool that can be used to modulate the transport of drugs, nutrients, and wastes in tissue engineering applications., (© 2024 The Author(s). Macromolecular Bioscience published by Wiley‐VCH GmbH.)

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.

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.

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., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest.

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.