Gradient Poly(ethylene glycol) Diacrylate and Cellulose Nanocrystals Tissue Engineering Composite Scaffolds via Extrusion Bioprinting

Abstract

Bioprinting has advanced drastically in the last decade, leading to many new biomedical applications for tissue engineering and regenerative medicine. However, there are still a myriad of challenges to overcome, with vast amounts of research going into bioprinter technology, biomaterials, cell sources, vascularization, innervation, maturation, and complex 4D functionalization. Currently, stereolithographic bioprinting is the primary technique for polymer resin bioinks. However, it lacks the ability to print multiple cell types and multiple materials, control directionality of materials, and place fillers, cells, and other biological components in specific locations among the scaffolds. This study sought to create bioinks from a typical polymer resin, poly(ethylene glycol) diacrylate (PEGDA), for use in extrusion bioprinting to fabricate gradient scaffolds for complex tissue engineering applications. Bioinks were created by adding cellulose nanocrystals (CNCs) into the PEGDA resin at ratios from 95/5 to 60/40 w/w PEGDA/CNCs, in order to reach the viscosities needed for extrusion printing. The bioinks were cast, as well as printed into single-material and multiple-material (gradient) scaffolds using a CELLINK BIOX printer, and crosslinked using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as the photoinitiator. Thermal and mechanical characterizations were performed on the bioinks and scaffolds using thermogravimetric analysis, rheology, and dynamic mechanical analysis. The 95/5 w/w composition lacked the required viscosity to print, while the 60/40 w/w composition displayed extreme brittleness after crosslinking, making both CNC compositions non-ideal. Therefore, only the bioink compositions of 90/10, 80/20, and 70/30 w/w were used to produce gradient scaffolds. The gradient scaffolds were printed successfully and embodied unique mechanical properties, utilizing the benefits of each composition to increase mechanical properties of the scaffold as a whole. The bioinks and gradient scaffolds successfully demonstrated tunability of their mechanical properties by varying CNC content within the bioink composition and the compositions used in the gradient scaffolds. Although stereolithographic bioprinting currently dominates the printing of PEGDA resins, extrusion bioprinting will allow for controlled directionality, cell placement, and increased complexity of materials and cell types, improving the reliability and functionality of the scaffolds for tissue engineering applications.

Rheological Aspects of Cellulose Nanomaterials: Governing Factors and Emerging Applications

“…CNCs were also combined with polymers (e.g., alginate, gelatin, and PEGDA) [250,251,253,255,256] or functional additives www.advmat.de www.advancedsciencenews.com (e.g., graphene quantum dots) [252] to prepare high-performance bioinks. The presence of S-CNCs increased the viscosity of polymers, leading to better printability and shape fidelity (Figure 10d,e).…”

“…Multiple formulations with varying PEGDA/S‐CNC ratios were extrusion printed into representative tissue scaffolds with gradient properties. [ 253 ] These formulations possessed sufficient yield stress and strong shear thinning response to generate dimensionally stable prints that were UV post‐cured into the final form. A Schiff base reaction was reported to crosslink a bioink composed of dialdehyde CNCs (D‐CNCs) and gelatin.…”

Advances in 3D bioprinting technology for cardiac tissue engineering and regeneration

“…For the past one decade, applications of 3D bioprinting technology in the field of cardiovascular repair and regeneration, particularly those aspiring to generate a holistic engineered heart tissue (HEHT) with long-term contractility for transplantation, have achieved significant progress. Notably, the fabrication of HEHT by a 3D bioprinting system, such as the prevailing extrusion-based 3D bioprinter [ 59 ], relies largely on precise depositions of cardiac related cell-laden polymerous bioink in a well-organized manner to strongly form the prototype-established route. The realistic design of this mechanical operation that redraws the anatomy and pump function of a mammalian heart has gradually deepened due to the micro-scale control progress of 3D printing technology itself and because of the cardiac-oriented developments of iPSCs and biomaterials [ 60 ].…”

Advances in the Application of Biomimetic Endometrium Interfaces for Uterine Bioengineering in Female Infertility

“…Several factors should be considered carefully, such as vascularization, native cell recruitment, and scar inhibition (Owusu-Akyaw et al, 2019). Cell seeding on the scaffold materials increases biological functions by prolonging cell survival and stimulating cell proliferation, differentiation and vascularization (Frost et al, 2019). Kim Y. Y. et al (2019) also used decidualized endometrial stromal cells (dEMSCs) encapsulated in hyaluronic acid (HA) hydrogel in a murine uterine infertility model.…”