A Tissue‐Penetrating Double Network Restores the Mechanical Properties of Degenerated Articular Cartilage

Abstract

Incorporation of an interpenetrating polymer network into an existing single polymer network enables augmentation of the original substrate’s mechanical properties, and translation of this concept from purely synthetic materials to natural-synthetic hybrid systems provides the opportunity to reinforce mechanical properties of bulk biological substrates. In many disease states, bodily tissues experience a deterioration of mechanical properties which renders them prone to further material failure. Herein, a tissue-supplementing technique is described in which an interpenetrating biomimetic hydrogel is polymerized in situ throughout cartilage tissue. The treatment restores the inferior compressive properties of osteoarthritic cartilage to that of healthy cartilage, preferentially localizing to weaker regions of tissue. Furthermore, the treatment technique preserves cartilage under harsh articulation conditions, showing promise as a materials-based treatment for early-stage osteoarthritis.

Reinforcement of articular cartilage with a tissue-interpenetrating polymer network reduces friction and modulates interstitial fluid load support

“…The differences in COF became statistically significant between 60 w/v% treated and non-treated tissue approximately half-way into the three-hour test (24% reduction in COF compared to non-treated tissue at the test’s completion), whereas the difference in COF between 20 w/v% and non-treated tissue demonstrated a non-statistically significant (p = 0.48) 5% reduction in COF compared to non-treated tissue. The IPN dose-dependence of the frictional response agrees with the observed dose-dependence of the compressive stiffness and wear-resistance as reported in our prior study, 36 and the IPN’s reduction of friction reported herein may be one of the primary reasons causing its improvement in wear-resistance. While the magnitude of COF is affected by the presence of IPN, the characteristic shapes of the three COF curves as a function of time are not statistically significant; all three curves possess similar COF equilibration time constants.…”

“…This attenuation of creep deformation (22% reduction by the test’s equilibrium) is related to the increased equilibrium stiffness that the IPN imparts. 36 Similar to the COF vs time profiles, the creep deformation time profiles do not statistically significantly differ in equilibration time constant τ ε (p = 0.33), with τ ε lengthened by 9% for the 60 w/v% treated compared to non-treated tissue. This increased time constant represents the increased time required for tissue to deform in response to the constant load applied, and likely originates from two underlying mechanisms.…”

“…We recently reported a new cartilage-reinforcing technique—administration of a GAG-inspired zwitterionic polymer 2-methacryloyloxyethyl phosphorylcholine (pMPC) that reconstitutes cartilage matrix hydrophilicity. 36 The treatment involves forming, through in-situ photopolymerization, a semi-synthetic interpenetrating polymer network (IPN) entangled with native collagen fibrils (Figure 1a) that increases the compressive stiffness and wear resistance of treated cartilage during accelerated wear testing against stainless steel when IFLS began high and was allowed to subside. The present study investigates the frictional response of IPN-treated cartilage sliding against IPN-treated cartilage and the effects of the interpenetrating polymer on the relationship between normalized strain values ( ε / ε eq ) and COF.…”

Tough high modulus hydrogels derived from carbon-nitride via an ethylene glycol co-solvent route

“…A comparison of E mod values of gels with literature is presented in Table S3 (ESI †). 3,13,14,[62][63][64] To investigate the fatigue resistance of EG gels and hydrogels, consecutive cyclic compression tests were performed. Standard force was recorded against true strain, which is the absolute change in plate distance, with an elongation of 50%.…”

“…At the same time, addition of the reinforcing agent increases the crosslinking density resulting in stronger interactions. Common approaches for improvement of hydrogels mechanical properties utilize double network systems, [12][13][14] nanofibers, 15 tetra armed-PEG crosslinked systems, 16,17 3D printing, 18 slide-ring gels, 19,20 and introduction of charged supports. 11,21,22 Double network systems are one of the first examples of reinforced hydrogels that consist of a tightly crosslinked first network and a loosely crosslinked secondary network.…”