3D Printing of Thermoresponsive Polyisocyanide (PIC) Hydrogels as Bioink and Fugitive Material for Tissue Engineering

Abstract

Despite the rapid and great developments in the field of 3D hydrogel printing, a major ongoing challenge is represented by the development of new processable materials that can be effectively used for bioink formulation. In this work, we present an approach to 3D deposit, a new class of fully-synthetic, biocompatible PolyIsoCyanide (PIC) hydrogels that exhibit a reverse gelation temperature close to physiological conditions (37 °C). Being fully-synthetic, PIC hydrogels are particularly attractive for tissue engineering, as their properties—such as hydrogel stiffness, polymer solubility, and gelation kinetics—can be precisely tailored according to process requirements. Here, for the first time, we demonstrate the feasibility of both 3D printing PIC hydrogels and of creating dual PIC-Gelatin MethAcrylate (GelMA) hydrogel systems. Furthermore, we propose the use of PIC as fugitive hydrogel to template structures within GelMA hydrogels. The presented approach represents a robust and valid alternative to other commercial thermosensitive systems—such as those based on Pluronic F127—for the fabrication of 3D hydrogels through additive manufacturing technologies to be used as advanced platforms in tissue engineering.

Tunable temperature‐ and shear‐responsive hydrogels based on poly(alkyl glycidyl ether)s

“…Stimuli‐responsive hydrogels belong to a unique class of materials that adapt to environmental cues such as pH, temperature, light and mechanical impetus . Temperature and shear stress are examples of two important stimuli responses that enable effective drug delivery, additive manufacturing and tissue engineering . A thermally reversible sol–gel response – wherein the hydrogel liquefies upon cooling – allows for facile loading of a hydrogel ink and homogeneous dispersion of heat‐insensitive drugs or additives in the liquid state .…”

3D Bioprinting in Skeletal Muscle Tissue Engineering

“…Thermoresponsive polymers such as poly( N ‐isopropylacrylamide) (pNIPAAM) have been used in bioinks because of their lower critical solution temperature (32 ° C) that allow the phase transition from liquid (<32 ° C ) to gel (>32 ° C ) . This reversible and fast gelling characteristic allows loading of cell‐laden ink in its liquid state in the printer cartridge, whereas the rapid gelation right after deposition onto a heated substrate maintains the shape of the printed constructs until the next crosslinking step . Other smart bioinks have been made with shear‐thinning property, therefore their viscosity decreases under increasing shear rate, allowing high printing fidelity since the polymer deposition is easier under pressure in the nozzle.…”

“…[94] This reversible and fast gelling characteristic allows loading of cell-laden ink in its liquid state in the printer cartridge, whereas the rapid gelation right after deposition onto a heated substrate maintains the shape of the printed constructs until the next crosslinking step. [63,95,96] Other smart bioinks have been made with shearthinning property, therefore their viscosity decreases under increasing shear rate, allowing high printing fidelity since the polymer deposition is easier under pressure in the nozzle. The use of shear thinning materials results in fast gelation after the pressure is released.…”

Bioengineering Liver Transplantation

“…PIC exhibits thermo-reversible behavior due to the hydrophobic interactions of the oligoglycol substituent present along its backbone, with a steep increase of the storage modulus (G') above 18 • C. As a water-soluble synthetic polymer, PIC mimics natural protein-based filaments. Its thermoreversible gelation property and cytocompatibility make PIC an ideal candidate for bioprinting technology [151]. The unique semiflexible properties combined with a length of several hundred nanometers have recently made it particularly attractive for LTE [139].…”