A versatile bioink for three-dimensional printing of cellular scaffolds based on thermally and photo-triggered tandem gelation

Abstract

Layer-by-layer bioprinting is a logical choice for the fabrication of stratified tissues like articular cartilage. Printing of viable organ replacements, however, is dependent on bioinks with appropriate rheological and cytocompatible properties. In cartilage engineering, photocrosslinkable glycosaminoglycan-based hydrogels are chondrogenic, but alone have generally poor printing properties. By blending the thermoresponsive polymer poly(N-isopropylacrylamide) grafted hyaluronan (HA-pNIPAAM) with methacrylated hyaluronan (HAMA), high-resolution scaffolds with good viability were printed. HA-pNIPAAM provided fast gelation and immediate post-printing structural fidelity, while HAMA ensured long-term mechanical stability upon photocrosslinking. The bioink was evaluated for rheological properties, swelling behavior, printability and biocompatibility of encapsulated bovine chondrocytes. Elution of HA-pNIPAAM from the scaffold was necessary to obtain good viability. HA-pNIPAAM can therefore be used to support extrusion of a range of biopolymers which undergo tandem gelation, thereby facilitating the printing of cell-laden, stratified cartilage constructs with zonally varying composition and stiffness.

Tuning the gelation of thermoresponsive gels

“…11 TRGs have many biomedical applications 12 including drug delivery [13][14][15][16][17][18][19][20][21] and tissue engineering as in-situ forming gels [22][23][24][25][26][27] and in 3-D bioprinting. [28][29][30][31] Furthermore with the increasing recent interest in 3-D printable materials and the need to control the rheology of the solution while printing 32, 33 the areas of potential usage of TRGs has increased since 3-D printing is applied to the manufacture of materials in various industries besides the medical industry, like aerospace, automotive, building and construction, marine, food industry and in manufacturing electronic and optical devices. [34][35][36] In TRGs applications it is highly important to be able to control the gelation point, i.e.…”

A flow perfusion bioreactor with controlled mechanical stimulation: Application in cartilage tissue engineering and beyond

“…This complex architecture of AC cannot be mimicked simply by encapsulating cells in hydrogels and/or seeding cells onto pre-formed polymeric scaffolds. Such methods do not allow for precise cell-suspension and orientation at the targeted location [120].…”

Advances in bioprinted cell-laden hydrogels for skin tissue engineering

“…These studies also demonstrated the possibility to determine and to reduce the shear stresses transmitted to the cells through experimental and numerical studies [17,19,30,46,127]. To address the unique requirements of extrusion bioprinting regarding the print fidelity and biological characteristics, research efforts have been focused on the development of bioinks exhibiting appropriate rheological, mechanical and biological properties [28,32,74,82,100,152,169,174]. A multitude of crosslinking mechanisms, including thermal gelation, ionic and photocrosslinking, have also been explored to induce the in situ gelation of printed materials with the ultimate goal of improving the mechanical properties, the shape fidelity and the formation of interconnected 3D pores throughout the construct [4,28,107], which still remains a major challenge.…”