Bioadhesive functional hydrogels: Controlled release of catechol species with antioxidant and antiinflammatory behavior

Mater Sci Eng C Mater Biol Appl. 2019 Dec:105:110040. doi: 10.1016/j.msec.2019.110040. Epub 2019 Jul 31.

Abstract

Chronic wounds are particularly difficult to heal and constitute an important global health care problem. Some key factors that make chronic wounds challenging to heal are attributed to the incessant release of free radicals, which activate the inflammatory system and impair the repair of the wound. Intrinsic characteristics of hydrogels are beneficial for wound healing, but the effective control of free radical levels in the wound and subsequent inflammation is still a challenge. Catechol, the key molecule responsible for the mechanism of adhesion of mussels, has been proven to be an excellent radical scavenger and anti-inflammatory agent. Our approach in this work lies in the preparation of a hybrid system combining the beneficial properties of hydrogels and catechol for its application as a bioactive wound dressing to assist in the treatment of chronic wounds. The hydrogel backbone is obtained through a self-covalent crosslinking between chitosan (Ch) and oxidized hyaluronic acid (HAox) in the presence of a synthetic catechol terpolymer, which is subsequently coordinated to Fe to obtain an interpenetrated polymer network (IPN). The structural analysis, catechol release profiles, in vitro biological behavior and in vivo performance of the IPN are analyzed and compared with the semi-IPN (without Fe) and the Ch/HAox crosslinked hydrogels as controls. Catechol-containing hydrogels present high tissue adhesion strength under wet conditions, support growth, migration and proliferation of hBMSCs, protect cells against oxidative stress damage induce by ROS, and promote down-regulation of the pro-inflammatory cytokine IL-1β. Furthermore, in vivo experiments reveal their biocompatibility and stability, and histological studies indicate normal inflammatory responses and faster vascularization, highlighting the performance of the IPN system. The novel IPN design also allows for the in situ controlled and sustained delivery of catechol. Therefore, the developed IPN is a suitable ECM-mimic platform with high cell affinity and bioactive functionalities that, together with the controlled catechol release, will enhance the tissue regeneration process and has a great potential for its application as wound dressing.

Keywords: Anti-inflammatory; Antioxidant; Catechol; Chitosan; Hyaluronic acid; In vivo.

MeSH terms

  • Adhesives / chemistry*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Catechols / pharmacology*
  • Cattle
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Chitosan / chemistry
  • Collagen / metabolism
  • Delayed-Action Preparations
  • Humans
  • Hyaluronic Acid / chemistry
  • Hydrogels / chemistry*
  • Interleukin-1beta / metabolism
  • Iron / chemistry
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Oxidation-Reduction
  • Polymers / chemistry
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Swine

Substances

  • Adhesives
  • Anti-Inflammatory Agents
  • Antioxidants
  • Catechols
  • Delayed-Action Preparations
  • Hydrogels
  • Interleukin-1beta
  • Polymers
  • Reactive Oxygen Species
  • Hyaluronic Acid
  • Collagen
  • Chitosan
  • Iron
  • catechol