Adhesive Hydrogel Building Blocks to Reconstruct Complex Cartilage Tissues.

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.

Emerging polymeric material strategies for cartilage repair.

Cartilage is found throughout the body, serving an array of essential functions. Owing to the limited healing capacity of cartilage, damage or degeneration is often permanent and so requires clinical intervention. Established surgical techniques generally rely on biological grafting. However, recent advances in polymeric materials provide an encouraging alternative to overcome limits of auto- and allografts. For regenerative engineering of cartilage, a polymeric scaffold ideally supports and instructs tissue regeneration while also providing mechanical integrity. Scaffolds direct regeneration via chemical and mechanical cues, as well as delivery and support of exogenous cells and bioactive factors. Advanced polymeric scaffolds aim to direct regeneration locally, replicating the heterogeneities of native tissues. Alternatively, new cartilage-mimetic hydrogels have potential to serve as synthetic cartilage replacements. Prepared as multi-network or composite hydrogels, the most promising candidates have simultaneously realized the hydration, mechanical, and tribological properties of native cartilage. Collectively, the recent rise in polymers for cartilage regeneration and replacement proposes a changing paradigm, with a new generation of materials paving the way for improved clinical outcomes.

Ultra-High Modulus Hydrogels Mimicking Cartilage of the Human Body.

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 1st network, a neutral 2nd network (capable of hydrophobic associations), and a cationic 3rd network. Collectively, these interactions act synergistically as effective, yet dynamic crosslinks. By tuning the concentration of the cationic 3rd 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).

Cartilage-like tribological performance of charged double network hydrogels.

A synthetic hydrogel material may offer utility as a cartilage replacement if it is able to maintain low friction in different sliding environments and achieve bulk mechanical properties to withstand the severe environment of the joint. In this work, we compared the tribological behavior of four double network (DN) hydrogels to that of fresh porcine cartilage in both water and fetal bovine serum (FBS). The DN hydrogels were comprised of a negatively charged 1st network and a 2nd network wherein comonomers of varying charge (i.e. neutral, positive, negative, and zwitterionic) were introduced at 10 wt% to an otherwise neutral network. A steel ball probe was used to perform microindentation tests to determine the surface elastic modulus of the samples and estimate their contact areas during sliding. Friction tests using a stationary probe with a stage that reciprocated at a range of speeds were performed to develop lubrication curves in both water and FBS. We found that the DN hydrogels with a neutral or zwitterionic 2nd network had the lowest friction and shear stresses, notably below that of cartilage. The differences in charge and structure of the samples were more evident in water than in FBS, as the lubrication responses for all the hydrogels spanned a wider range of values. In FBS, the lubrication responses were pushed towards elasto-hydrodynamics with nearly all friction coefficient values falling below 0.3. This indicates that the FBS interacts with the hydrogels and cartilage samples in a similar manner as that of cartilage by maintaining a robust layer of solution at the interface during sliding. These DN hydrogels prove to fulfill, and in some cases surpass, the lubrication demands for cartilage replacement in load bearing joints.

Spatially Controlled Templated Hydrogels for Orthopedic Interfacial Tissue Regeneration.

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.