title: Injectable and Self-Healing Dynamic Hydrogels Based on Metal(I)-Thiolate/Disulfide Exchange as Biomaterials with Tunable Mechanical Properties.
abstract: 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.
authors.affiliation: Materials Division, IK4-CIDETEC Research Centre , Paseo Miramón 196, Donostia-San Sebastián 20009, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Casuso
authors.affiliation: Materials Division, IK4-CIDETEC Research Centre , Paseo Miramón 196, Donostia-San Sebastián 20009, Spain.
authors.forename: Ibon
authors.initials: I
authors.lastname: Odriozola
authors.affiliation: Materials Division, IK4-CIDETEC Research Centre , Paseo Miramón 196, Donostia-San Sebastián 20009, Spain.
authors.forename: Adrián
authors.initials: A
authors.lastname: Pérez-San Vicente
authors.affiliation: Materials Division, IK4-CIDETEC Research Centre , Paseo Miramón 196, Donostia-San Sebastián 20009, Spain.
authors.forename: Iraida
authors.initials: I
authors.lastname: Loinaz
authors.affiliation: Materials Division, IK4-CIDETEC Research Centre , Paseo Miramón 196, Donostia-San Sebastián 20009, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Cabañero
authors.affiliation: Materials Division, IK4-CIDETEC Research Centre , Paseo Miramón 196, Donostia-San Sebastián 20009, Spain.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Grande
authors.affiliation: Materials Division, IK4-CIDETEC Research Centre , Paseo Miramón 196, Donostia-San Sebastián 20009, Spain.
authors.forename: Damien
authors.initials: D
authors.lastname: Dupin
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006046:Gold / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000737:chemistry; D012212:Rheology; D012834:Silver / Q000737:chemistry; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D004220:Disulfides; D020100:Hydrogels; D013438:Sulfhydryl Compounds; D012834:Silver; D011092:Polyethylene Glycols; D006046:Gold