Ag NPs incorporated self-healable thermoresponsive hydrogel using precise structural “Interlocking” complex of polyelectrolyte BCPs: A potential new wound healing material

Abstract

There have been great interests in the development of new smart materials for the wound-healing application. Herein, we have designed a new wound-healable material based on thermoresponsive multi-layered micellar interpolyelectolyte complex (IPEC) hydrogel. The polyelectrolyte BCPs were prepared via reversible addition-fragmentation chain-transfer (RAFT) polymerization. The combination of inner thiolated cationic poly(2-hydroxyethyl methacrylate-block-(2-(methacryloyloxy)ethyltrimethyl ammonium chloride) (PHEMA-b-PMTAC) BCP stabilized Ag NPs and outer anionic thermoresponsive poly(N-isopropylacrylamide-block-sodium 4-vinylbenzenesulfonate) (PNIPAAm-b-PSS) BCP moiety of the IPEC provides self-healing property to the complex via ionic interaction. The morphology of the resulting IPEC was investigated by FESEM, AFM, and HRTEM analyses. The spray-on thermoresonsive IPEC was found to form self-standing hydrogel at the wound site above its lower critical solution temperature (LCST at 33 °C), as determined using temperature-responsive DLS analysis. The Ag NPs embedded hydrogel showed a catastrophic effect against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria which was confirmed using Live-dead assay (DAPI-PI analysis), flow cytometry (FACS) study and morphological analyses. This ensures the prevention of wound infection. Upon application of this Ag NPs embedded IPEC in the wound site of Wistar rats (in vivo study), the re-epithelialization process was observed to be facilitated leading to wound healing. The CD31 and Collagen IV markers were used in the immunohistochemistry (IHC) study of the wound closure process. The combination of the qRT-PCR and IHC study suggested that the Ag NPs incorporated thermogel can have application as anti-flammation and angiogenic material. The multifunctional activities of this new IPEC based hydrogel can shed light in the field of wound dressing application.