Self-Healing Dynamic Hydrogel as Injectable Shock-Absorbing Artificial Nucleus Pulposus.

The intervertebral discs (IVDs) provide unique flexibility to the spine and exceptional shock absorbing properties under impact. The inner core of the IVD, the nucleus pulposus (NP) is responsible for this adaptive behavior. Herein, we evaluate an injectable, self-healing dynamic hydrogel (DH) based on gold(I)-thiolate/disulfide (Au-S/SS) exchange as NP replacement in a spine motion segment model. For the first time, we report the application of dynamic covalent hydrogels inside biological tissues. The dynamic exchange between Au-S species and disulfide bonds (SS) resulted in self-healing ability and frequency-dependent stiffness of the hydrogel, which was also confirmed in spine motion segments. Injection of preformed DH into nucleotomized IVDs restored the full biomechanical properties of intact IVDs, including the stiffening effect observed at increasing frequencies, which cannot be achieved with conventional covalent hydrogel. DH has the potential to counteract IVD degeneration associated with high frequency vibrations. Self-healing properties, confirmed by rheology studies and macroscopic observation after injection, were required to inject preformed DH, which recovered its mechanical integrity and microstructure to act as an artificial NP. On the other hand, covalent hydrogel did not show any restoration of NP properties as this conventional material suffered irreversible damages after injection, which demonstrates that the dynamic properties are crucial for this application. The persistence of DH in the IVD space following cyclic high-frequency loading, confirmed by tomography after mechanical testing, suggests that this material would have long life span as an injectable NP replacement material.

Injectable and Self-Healing Dynamic Hydrogels Based on Metal(I)-Thiolate/Disulfide Exchange as Biomaterials with Tunable Mechanical Properties.

Despite numerous strategies involving dynamic covalent bonds to produce self-healing hydrogels with similar frequency-dependent stiffness to native tissues, it remains challenging to use biologically relevant thiol/disulfide exchange to confer such properties to polymeric networks. Herein, we report a new method based on Metal(I) [Au(I) or Ag(I)] capping to protect thiolates from aerial oxidation without preventing thiolate/disulfide exchange. Dynamic hydrogels were readily prepared by injecting simultaneously aqueous solutions of commercially available HAuCl4 and 4-arm thiol-terminated polyethylene glycol [(PEGSH)4], resulting in a network containing a mixture of Au(I)-thiolate (Au-S) and disulfide bonds (SS). While the dynamic properties of the hydrogel were closely dependent on the pH, the mechanical properties could be easily tuned by adjusting (PEGSH)4 concentration and amount of Au-S, as judged by dynamic rheology studies. Permanent Au-S/SS exchange at physiological pH conferred self-healing behavior and frequency-dependent stiffness to the hydrogel. In addition, in vitro studies confirmed that Au-based dynamic material was not cytotoxic to human dermal fibroblasts, demonstrating its potential use as a medical device. Dynamic hydrogels obtained using Ag(I) ions demonstrated that the exchange reaction was not affected by the nature of the Metal(I) capping. Finally, this efficient thiolate capping strategy offers a simple way to produce injectable and self-healing dynamic hydrogels from virtually any thiol-containing polymers.

Aurophilically cross-linked "dynamic" hydrogels mimicking healthy synovial fluid properties.

We report a new supramolecular dynamic hydrogel, based on a new concept of reversible aurophilic cross-linkers, mimicking the rheological behaviour of healthy synovial fluid under physiological conditions with good cell viability.

Designing neutral metallophilic hydrogels from di- and tripeptides.

Here we report the metallophilic attraction driven gel-forming capability of four cysteine-containing short peptides at neutral pH. Such peptides were designed to have an isoelectric point (pI) close to 7, aided by the introduction of an arginine unit with its highly basic guanidinium group.

Converting drugs into gelators: supramolecular hydrogels from N-acetyl-L-cysteine and coinage-metal salts.

Here we present the concept of metallophilic hydrogels, supramolecular systems in which the gelator species are metal-thiolates that self-assemble through metallophilic attractions. The principle is applied for a small drug, the mucolytic agent N-acetyl-l-cysteine (NAC), which readily forms hydrogels in the presence of Au(iii), Ag(i) and Cu(ii) salts. The resulting transparent hydrogels present pH induced sol/gel transition. Scanning electron microscopy (SEM) measurements reveal a microporous structure in form of flakes for the three of them. The low pH at which these hydrogels are formed (pH < 4) limits their direct use as drug-delivery systems, but still this system constitutes a novel method for easy and fast conversion of small drugs into potent hydrogelators. Future developments will help to fully develop the idea in order to create a new class of supramolecular drug-delivery systems.