Functional Self-healing Hydrogels Based on Dynamic Molecular Interactions for Biomedical Applications

  • Author / Creator
    Wang, Wenda
  •      Self-healing hydrogels can autonomously heal from damage to preserve their integrity and functionalities which hold great promises in a wide range of applications. Different types of dynamic molecular interactions have been explored to develop self-healing hydrogels. Nevertheless, it remains a challenge to integrate multifunctionalities in one “smart” hydrogel platform based on different requirements in diverse biomedical applications. In addition, the molecular level understanding of different dynamic molecular interaction mechanisms is limited. In this thesis, a review of different self-healing mechanisms and some typical biomedical applications of self-healing hydrogels is first presented, followed by three original studies of developing multifunctional self-healing hydrogels for different potential biomedical applications and investigating the associated molecular interaction mechanisms. 
    Self-healing hydrogels with injectability, multi-stimuli-responsive and antimicrobial properties are highly desired for wound healing. In the first project, an injectable self-healing hydrogel with dual temperature-pH responsive and antimicrobial properties was developed based on dynamic Schiff base reactions between a synthetic multifunctional ABA triblock copolymer gelator, poly{(4-formylphenyl methacrylate)-co-[[2-(methacryloyloxy)ethyl] trimethylammonium chloride]}-b-poly(N-isopropylacrylamide)-b-poly{(4-formylphenyl methacrylate)-co-[[2-(methacryloyloxy)ethyl] trimethylammonium chloride]} (PFMNMF) and polyethylenimine (PEI). The self-healing capability was characterized by rheology tests and the associated molecular interaction mechanism was studied using a surface forces apparatus (SFA). The hydrogel demonstrated excellent injectability as well as sensitive dual temperature-pH responsiveness. In addition, the hydrogel could also effectively inhibit the growth of both Gram-negative and Gram-positive bacteria (Escherichia coli and Staphylococcus aureus), while showed low cytotoxicity to both fibroblast and cancer cells (MRC-5 and HeLa). Such multifunctional self-healing hydrogel can be potentially applied as wound dressing material.
    The development of biological tissue-like hydrogels with both self-healing and strain-stiffening capabilities is of great significance in various biomedical and engineering applications. In the second project, a biomimetic self-healing strain-stiffening flexible hydrogel was developed based on the dynamic boronic acid-diol interactions between diphenylboronic acid-terminated telechelic poly(ethylene glycol) (DPB-PEG) and a glycopolymer, poly(acrylamide-co-2-lactobionamidoethyl methacrylamide) (P(AM-co-LAMEA)). The hydrogel can be reversibly and repeatedly stiffened up to 8 times of its original modulus as it is strained, without showing mechanical hysteresis. In addition, the damaged hydrogel can repeatedly self-heal within seconds and fully retains the strain-stiffening capability. The associated dynamic molecular interactions were quantitatively measured using a SFA. Based on the biomimetic characteristics as well as the excellent biocompatibility, the hydrogel served as an ideal cell culture matrix to mimic the in vivo mechanical environments for 3D cell culture.
    In the third project, an injectable self-healing hydrogel with anti-biofouling property was developed as internal wound dressing for the treatment of gastric perforation. The hydrogel was designed based on the biological environment-adaptive supramolecular self-assembly of an ABA triblock copolymer, employing a central poly(ethylene glycol) (PEG) block and terminal thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) block with pH sensitive acryloyl-6-aminocaproic acid (A6ACA) moieties randomly incorporated. Due to the thermo-sensitivity, the hydrogel could be rapidly formed at the targeted site after simple injection. The formed hydrogel dressing could smartly utilize the acidic environment to self-heal from repeated damage through the synergy of hydrophobic and pH-mediated hydrogen bonding interactions. The associated molecular interaction mechanism was studied using a SFA. Besides, the hydrogel exhibits excellent anti-biofouling performance against microorganism attachment. The in vivo rat model demonstrated the remarkable capabilities of the hydrogel dressing to simplify surgical procedures, reduce postoperative complications as well as enhance the healing process of gastric perforation compared with the conventional omental implantation. 
    This thesis work develops three novel multifunctional self-healing hydrogels based on different dynamic molecular interactions for biomedical applications, as well as investigates the self-healing mechanisms from the perspective of intermolecular interactions and surface forces. This work not only expands the applicability of self-healing hydrogels in some new biomedical applications, but also provides fundamental insights into the development of multifunctional self-healing hydrogel in various biomedical applications.

  • Subjects / Keywords
  • Graduation date
    Fall 2021
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.