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).

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Scaffolds that recapitulate the spatial complexity of orthopedic interfacial tissues are essential to their regeneration. This requires a method to readily and flexibly produce scaffolds with spatial control over physical and chemical properties, without resulting in hard interfaces. Herein, we produced hydrogel scaffolds with spatially tunable arrangements and chemistries (SSTACs). Using solvent-induced phase separation/fused salt templating (SIPS/salt), scaffold elements are initially prepared with a tunable pore size and with one or more UV-reactive macromers. After trimming to the desired dimensions, these are physically configured and fused together to form the SSTACs. Using this method, three SSTAC designs were prepared, including one that mimicked the osteochondral interface. Bright-field/fluorescent microscopy revealed spatial control of pore size and chemical composition across a relatively smooth and integrated interface, regardless of layer composition. An interface formed by a SSTAC was determined to withstand a similar shear force to an analogous scaffold with no interface.

The recent rise of polymeric materials for cartilage regenerative engineering and tissue-mimetic synthetic replacements is paving way for a new generation of materials with improved clinical outcomes.

Cartilage has an intrinsically low healing capacity, thereby requiring surgical intervention. However, limitations of biological grafting and existing synthetic replacements have prompted the need to produce cartilage-mimetic substitutes. Cartilage tissues perform critical functions that include load bearing and weight distribution, as well as articulation. These are characterized by a range of high moduli (≥1 MPa) as well as high hydration (60–80%). Additionally, cartilage tissues display spatial heterogeneity, resulting in regional differences in stiffness that are paramount to biomechanical performance. Thus, cartilage substitutes would ideally recapitulate both local and regional properties. Toward this goal, triple network (TN) hydrogels were prepared with cartilage-like hydration and moduli as well as adhesivity to one another. TNs were formed with either an anionic or cationic 3rd network, resulting in adhesion upon contact due to electrostatic attractive forces. With the increased concentration of the 3rd network, robust adhesivity was achieved as characterized by shear strengths of ∼80 kPa. The utility of TN hydrogels to form cartilage-like constructs was exemplified in the case of an intervertebral disc (IVD) having two discrete but connected zones. Overall, these adhesive TN hydrogels represent a potential strategy to prepare cartilage substitutes with native-like regional properties.