Fabrication of Mechanically Robust PEG-Based Hydrogels for 3D Printing and Injection

Abstract

Hydrogels, due to their unique characteristics, are ideal candidates for tissue engineering and regenerative medicine applications. However, their inherent softness and brittleness, resulting from their high water content and the nonuniform structure formed during the crosslinking process, can limit their applications in load-bearing tissues such as cartilage, tendons, and ligaments. The overall aim of this work was to enhance the mechanical performance of poly(ethylene glycol) (PEG)-based hydrogels using two distinct and straightforward strengthening strategies compatible with injection and various light-based 3D printing technologies. In Chapter 3, the strategy of creating relatively uniform networks using nucleophilic thiol-yne chemistry was applied to improve the mechanical performance of hydrogels by minimizing structural defects, which act as stress concentration zones during deformation. It was demonstrated that the mechanical properties could be tuned by varying parameters such as polymer content, molecular weight, and the architecture of the building blocks. To evaluate the effect of network uniformity on hydrogel mechanics, relatively non-uniform hydrogels were also prepared using identical building blocks but crosslinked via UV light. The results showed that the relatively uniform PBS-crosslinked gels were mechanically more robust than their UV-crosslinked counterparts, despite using the same building blocks. Furthermore, the mechanical properties correlated well with the crosslink and entanglement densities predicted by the Rubinstein– Panyukov model. Continuing with the strategy of fabricating relatively uniform hydrogels, Chapter 4 explored thiol-norbornene chemistry to create PEG-based gels. A comprehensive library of hydrogels was developed by varying the polymer content, the molecular weight of PEG-Norbornene and PEG-Thiol crosslinkers, and the molar ratio of reactive end groups. The structure-property relationships in these hydrogels were systematically analyzed, demonstrating that robust formulations suitable for loadbearing applications could be achieved. Additionally, it was shown that, regardless of formulation, these hydrogels exhibited rapid gelation kinetics, solidifying within seconds of light illumination. In Chapter 5, the photocurable hydrogel resins developed in Chapter 4 were utilized for injection and processing via two advanced light-based 3D printing technologies: digital light processing (DLP) and volumetric printing (VP). These resins were proved highly suitable for these applications due to their fast gelation kinetics upon light exposure. However, modifications were necessary to meet the specific requirements of each printing technology. The fast fabrication of complex structures (<32 seconds) without any supporting elements was demonstrated via VP, outperforming conventional layer-based fabrication methods. Additionally, the printed structures were mechanically robust immediately after fabrication, requiring no post-printing curing. In Chapter 6, an interpenetrating network (IPN) strategy was employed to create robust hydrogels by combining the thiol-yne PEG networks developed in Chapter 3 with sodium alginate networks using a straightforward one-pot preparation method. The effects of various parameters—such as the uniformity of the PEG network, the order of network formation, the characteristics of alginate, and the building blocks used—on the reinforcing effects were systematically studied. While the addition of alginate enhanced the elastic modulus and maximum stress in some formulations, its most pronounced effect was on the fracture energy of the gels. The findings of this chapter provide valuable insights into designing hydrogel formulations tailored to specific application requirements.