A Printable Photopolymerizable Thermosensitive p(HPMAm‐lactate)‐PEG Hydrogel for Tissue Engineering

Abstract

Bioprinting is a new technology in regenerative medicine that allows the engineering of tissues by specific placement of cells in biomaterials. Importantly, the porosity and the relatively small dimensions of the fibers allow rapid diffusion of nutrients and metabolites. This technology requires the availability of hydrogels that ensure viability of encapsulated cells and have adequate mechanical properties for the preparation of structurally stable and well-defined three-dimensional constructs. The aim of this study is to evaluate the suitability of a biodegradable, photopolymerizable and thermosensitive A–B–A triblock copolymer hydrogel as a synthetic extracellular matrix for engineering tissues by means of three dimensional fiber deposition. The polymer is composed of poly(N-(2-hydroxypropyl)methacrylamide lactate) A-blocks, partly derivatized with methacrylate groups, and hydrophilic poly(ethylene glycol) B-blocks of a molecular weight of 10 kDa. Gels are obtained by thermal gelation and stabilized with additional chemical cross-links by photopolymerization of the methacrylate groups coupled to the polymer. A power law dependence of the storage plateau modulus of the studied hydrogels on polymer concentration is observed for both thermally and chemically cross-linked hydrogels. The hydrogels demonstrated mechanical characteristics similar to natural semi-flexible polymers, including collagen. Moreover, the hydrogel shows suitable mechanical properties for bioprinting, allowing subsequent layer-by-layer deposition of gel fibers to form stable constructs up to at least 0.6 cm (height) with different patterns and strand spacing. The resulting constructs have reproducible vertical porosity and the ability to maintain separate localization of encapsulated fluorescent microspheres. Moreover, the constructs show an elastic modulus of 119 kPa (25 wt% polymer content) and a degradation time of approximately 190 days. Furthermore, high viability is observed for encapsulated chondrocytes after 1 and 3 days of culture. In summary, we conclude that the evaluated hydrogel is an interesting candidate for bioprinting applications

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.…”

Advances in bioprinted cell-laden hydrogels for skin tissue engineering

“…In this versatile technology, cell-laden polymeric solutions [28,154], decellularized ECM components [73], cell suspensions [68], microcarriers [162] or tissue spheroids [185] are loaded into standard disposable syringes, and printed onto a building platform driven by pneumatic (pressurized air), mechanical (piston or screw) or solenoid (electrical pulses)-based dispensing systems [76,111,125,137]. An important advantage of extrusion bioprinting is the ability to print highly viscous polymer solutions containing a wide range of cell densities (up 10 7 cells mL -1 ) [92,182].…”

“…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.…”

Chemical crosslinking of acrylic acid to form biocompatible pH sensitive hydrogel reinforced with cellulose nanocrystals (CNC)

“…In recent years, tremendous amount of research attention had been focused on the "smart" polymer materials especially hydrogel that were able to response to external stimuli such as pH, temperature, electric and magnetic field by altering their volume and properties [1][2][3].With inherent characteristics such as hydrophilicity, sensitivities towards external stimuli, biocompatibility and soft elastomeric nature make hydrogel promising materials for a broad range of applications including sensors, drug delivery and tissue engineering [4][5][6].…”