Self-Healing Conductive Injectable Hydrogels with Antibacterial Activity as Cell Delivery Carrier for Cardiac Cell Therapy

Abstract

Cell therapy is a promising strategy to regenerate cardiac tissue for myocardial infarction. Injectable hydrogels with conductivity and self-healing ability are highly desirable as cell delivery vehicles for cardiac regeneration. Here, we developed self-healable conductive injectable hydrogels based on chitosan-graft-aniline tetramer (CS-AT) and dibenzaldehyde-terminated poly(ethylene glycol) (PEG-DA) as cell delivery vehicles for myocardial infarction. Self-healed electroactive hydrogels were obtained after mixing CS-AT and PEG-DA solutions at physiological conditions. Rapid self-healing behavior was investigated by rheometer. Swelling behavior, morphology, mechanical strength, electrochemistry, conductivity, adhesiveness to host tissue and antibacterial property of the injectable hydrogels were fully studied. Conductivity of the hydrogels is ∼10(-3) S·cm(-1), which is quite close to native cardiac tissue. Proliferation of C2C12 myoblasts in the hydrogel showed its good biocompatibility. After injection, viability of C2C12 cells in the hydrogels showed no significant difference with that before injection. Two different cell types were successfully encapsulated in the hydrogels by self-healing effect. Cell delivery profile of C2C12 myoblasts and H9c2 cardiac cells showed a tunable release rate, and in vivo cell retention in the conductive hydrogels was also studied. Subcutaneous injection and in vivo degradation of the hydrogels demonstrated their injectability and biodegradability. Together, these self-healing conductive biodegradable injectable hydrogels are excellent candidates as cell delivery vehicle for cardiac repair.

Cytocompatible, Injectable, and Electroconductive Soft Adhesives with Hybrid Covalent/Noncovalent Dynamic Network

“…Various characteristics, such as swelling degree, water content, stiffness, porosity, viscoelastic properties, and biocompatibility can be tailored for different applications. [8][9][10] Conductive polymers, such as polypyrrole (PPy), polyaniline (PAni), and poly (3,4-ethylenedioxythiophene) (PEDOT), have been used in the synthesis of electroconductive hydrogels due to their high conductivity and ease of processing. [4][5][6][7] Electroconductive hydrogels can be used in bioelectrical interfaces as bioresponsive electrodes, substrates that facilitate the electrical stimulation of cells or tissues (neuron or muscle), biosensors, implants, or for drug delivery under electrical stimulation.…”

A self-healing hydrogel as an injectable instructive carrier for cellular morphogenesis

“…More recently, several self-healing hydrogels were developed as injectable vehicles for cell delivery [36–38]. For example, Burdick’s group developed a self-healing hyaluronic acid hydrogel using dynamic host-guest interactions for 3T3 fibroblasts and mesenchymal stem cells [39,40].…”

“…Chen et al synthesized self-healing hydrogels via dynamic Schiff base reaction between oxidized sodium alginate and N-carboxyethyl chitosan, for delivery of neural stem cells [41]. In addition, there are series of polysaccharide-based self-healing hydrogels reported for culturing or delivering a wide range of cell types, including fibroblasts, HeLa cells, chondrocytes, marrow stem cells, and so on [26,32,36,42,43]. Nonetheless, despite the high cell viability of these self-healing hydrogels, most cells encapsulated in them are observed as invariably rounded shapes without cell-cell communications, even following a long culture period.…”

Self-Healing Hydrogels as Biomedical Scaffolds for Cell, Gene and Drug Delivery

“…In order to meet the demands of the scaffold, the adoptive material should be harmless for the living body. The most widely used are the simple chain polymer, such as, polyethylene glycol (PEG), polyacrylic acid (PAA), polyvinyl alcohol (PVA), which have clear structure and modification [22,38] . Another important kind is the derivative polymer from the nature, polypeptide and polysaccharide, such as collagen, hyaluronic acid, alginate, gelatin, glucose, chitosan, chitin and cellulose [22,[39][40][41][42][43] .…”