Mechanobiological Interactions between Dynamic Compressive Loading and Viscoelasticity on Chondrocytes in Hydrazone Covalent Adaptable Networks for Cartilage Tissue Engineering

Abstract

Mechanobiological cues influence chondrocyte biosynthesis and are often used in tissue engineering applications to improve the repair of articular cartilage in load‐bearing joints. In this work, the biophysical effects of an applied dynamic compression on chondrocytes encapsulated in viscoelastic hydrazone covalent adaptable networks (CANs) is explored. Here, hydrazone CANs exhibit viscoelastic loss tangents ranging from (9.03 ± 0.01) 10–4 to (1.67 ± 0.09) 10–3 based on the molar percentages of alkyl‐hydrazone and benzyl‐hydrazone crosslinks. Notably, viscoelastic alkyl‐hydrazone crosslinks improve articular cartilage specific gene expression showing higher SOX9 expression in free swelling hydrogels and dynamic compression reduces hypertrophic chondrocyte markers (COL10A1, MMP13) in hydrazone CANs. Interestingly, dynamic compression also improves matrix biosynthesis in elastic benzyl‐hydrazone controls but reduces biosynthesis in viscoelastic alkyl‐hydrazone CANs. Additionally, intermediate levels of viscoelastic adaptability demonstrate the highest levels of matrix biosynthesis in hydrazone CANs, demonstrating on average 70 ± 4 µg of sulfated glycosaminoglycans per day and 31 ± 3 µg of collagen per day over one month in dynamic compression bioreactors. Collectively, the results herein demonstrate the role of matrix adaptability and viscoelasticity on chondrocytes in hydrazone CANs during dynamic compression, which may prove useful for tissue engineering applications in load‐bearing joints.

Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling

“…The significant genes are listed in Table 2 and Fig. 3 E. We found that the expression of mineralization markers such as BGN, COL11A1 , and COL10A1 were significantly increased [ [30] , [31] , [32] , [33] ]. Similarly, the expression of vascular and neurological differentiation markers such as COL8A2 and ANKRD1 also increased to a certain extent [ 34 , 35 ].…”

Polymeric Hydrogels for Controlled Drug Delivery to Treat Arthritis

“…In a recent study by Richardson et al, hydrazine covalent adaptable network (CAN) hydrogel was synthesized from 8-arm tripentaerythritol PEG macromers with reactive hydrazine, alkyl-aldehyde, and benzaldehyde end groups and showed excellent viscoelastic properties with a higher value of loss tangents with a decrease in angular frequency. Notably, chondrocyte biosynthesis results illustrated the higher matrix biosynthesis levels of cartilaginous sulfated GAGs and collagen over a one-month period, suggesting its practicality in cell-mediated remodeling and CTE applications in arthritis treatment [ 102 ].…”

“…In recent years, various modifications of hydrogel systems have been investigated for loading cells and cartilage regeneration [ 143 ]. Additionally, cell-laden hydrogels may be combined with anti-inflammatory drugs and biological cues (i.e., growth factors, peptides, and siRNAs) to maintain the chondrogenic phenotype, enhance cell–matrix interaction, generate hyaline neotissues in cartilage focal defects, and alleviate inflammation [ 97 , 102 , 144 , 145 ].…”

“…In particular, hybrid hydrogels comprising both natural as well as synthetic components such as glycol chitosan/benzaldehyde-functionalized PEG [ 112 ], HAMA/pluronic nano-micelli [ 113 ], alginate-poloxamer/SF [ 115 ], PEG/SF [ 119 ], PEG/gelatin-norbornene [ 145 ] as well as MMP-sensitive PEG hydrogels [ 97 ] and hydrazone CANs [ 102 ] have been developed. These hybrid hydrogels facilitate long-lasting viability, maintain cellular phenotype, and promote proliferation with the generation of cartilage ECM including aggrecan, decorin, and collagen type II.…”

“…Recently, Richardson et al designed a viscoelastic PEG-based hydrazone CAN, which was seen as a dynamic compression bioreactor for chondrocyte encapsulation. The developed hydrazone CAN facilitated cartilage ECM synthesis under an intermediate level of viscoelastic adaptability and induced the highest matrix biosynthesis levels of cartilaginous sulfated GAGs and an average of 31 ± 3 µg of collagen per day over one month in chondrocyte culture under dynamic compressive loading [ 102 ].…”