Ultra‐High Modulus Hydrogels Mimicking Cartilage of the Human Body

Abstract

The human body is comprised of numerous types of cartilage with a range of high moduli, despite their high hydration. Owing to the limitations of cartilage tissue healing and biological grafting procedures, synthetic replacements have emerged but are limited by poorly matched moduli. While conventional hydrogels can achieve similar hydration to cartilage tissues, their moduli are substantially inferior. Herein, triple network (TN) hydrogels are prepared to synergistically leverage intra-network electrostatic repulsive and hydrophobic interactions, as well as inter-network electrostatic attractive interactions. They are comprised of an anionic 1 st network, a neutral 2 nd network (capable of hydrophobic associations), and a cationic 3 rd network. Collectively, these interactions act synergistically as effective, yet dynamic crosslinks. By tuning the concentration of the cationic 3 rd network, these TN hydrogels achieve high moduli of ≈1.5 to ≈3.5 MPa without diminishing cartilage-like water contents (≈80%), strengths, or toughness values. This unprecedented combination of properties poises these TN hydrogels as cartilage substitutes in applications spanning articulating joints, intervertebral discs (IVDs), trachea, and temporomandibular joint disc (TMJ).

Emerging polymeric material strategies for cartilage repair

“…Table 5 Recent studies of polymeric hydrogel materials for synthetic cartilage replacements [131][132][133][134][135][136][137][138][139][140][141][142][143][144][145][146][147][148] Study Material…”

“…Cooper, 2016; 145 Cooper, 2017; 146 Makela, 2018 147 PMPC | Means, 2019; 131 Bonyadi, 2021; 132 Demott, 2022; [133][134][135][136] Demott, 2022; 137 Demott, 2022 138 PAMPS/P(NIPAAm-co-AAm) | PAMPS/P(NIPAAm-co-AAm) PAMPS/P(NIPAAm-co-AAm)/PAAm PAMPS/P(NIPAAm-co-AAm)/ PAPTAC PAMPS/P(NIPAAm-co-AAm)/ [PATPAC or PAMPS] Milner, 2018 139 PAMPS/PAAm/PMPC | Milovanovic, 2021 144 PDMA -calcium phosphate | Patel 148 Hyaluronic acid | Xu, 2018 143 PVA -aramid nanofibers | Yang, 2017 140 PAMPS-LAPONITE s /PAAm | Yang, 2020; 141 Zhao, 2022; 142 Bacterial cellulose -PVA -PAMPS |…”

“…Thus, Demott et al modified this DN hydrogel through incorporation of a cationic 3rd network of poly((3-acrylamidopropyl)trimethylammonium chloride) (PAPTAC) (PAMPS/P(NIPAAm- co -AAm)/PAPTAC). 137 These resulting TN hydrogels leveraged a harmony of electrostatic repulsion within the 1st network, hydrophobic associations within the 2nd network, and electrostatic attraction between the 1st and 3rd network. Accordingly, unprecedented tunable moduli of up to ∼3 MPa were obtained along with a strength of ∼30 MPa and hydration of ∼80%.…”

Adhesive Hydrogel Building Blocks to Reconstruct Complex Cartilage Tissues

“…Multinetwork hydrogels offer a strategy to achieve robust mechanical properties. − Recently, our group reported triple network (TN) hydrogels that leveraged both electrostatic and hydrophobic interactions to achieve unprecedented, cartilage-matching moduli (∼1 to ∼3 MPa) and hydration (∼80%) . The synergy and dynamic nature of these physical cross-links also afforded high strength and toughness.…”

“…The NIPAAm units of the 2 nd network provided hydrophobic interactions. To ensure dimensional stability (i.e., no swelling/deswelling) under physiologic conditions, the volume phase transition temperature (VPTT) was tuned beyond the physiologic range through the copolymerization of AAm in the 2 nd network. , Despite their cartilage-like hydration and moduli, these TN-APTAC hydrogels do not mimic the regional properties exhibited by most cartilaginous tissues.…”