Flow behavior prior to crosslinking: The need for precursor rheology for placement of hydrogels in medical applications and for 3D bioprinting

Abstract

Hydrogels-water swollen cross-linked networks-have demonstrated considerable promise in tissue engineering and regenerative medicine applications. However, ambiguity over which rheological properties are needed to characterize these gels before crosslinking still exists. Most hydrogel research focuses on the performance of the hydrogel construct after implantation, but for clinical practice, and for related applications such as bioinks for 3D bioprinting, the behavior of the pre-gelled state is also critical. Therefore, the goal of this review is to emphasize the need for better rheological characterization of hydrogel precursor formulations, and standardized testing for surgical placement or 3D bioprinting. In particular, we consider engineering paste or putty precursor solutions (i.e., suspensions with a yield stress), and distinguish between these differences to ease the path to clinical translation. The connection between rheology and surgical application as well as how the use of paste and putty nomenclature can help to qualitatively identify material properties are explained. Quantitative rheological properties for defining materials as either pastes or putties are proposed to enable easier adoption to current methods. Specifically, the three-parameter Herschel-Bulkley model is proposed as a suitable model to correlate experimental data and provide a basis for meaningful comparison between different materials. This model combines a yield stress, the critical parameter distinguishing solutions from pastes (100-2000 Pa) and from putties (>2000 Pa), with power law fluid behavior once the yield stress is exceeded. Overall, successful implementation of paste or putty handling properties to the hydrogel precursor may minimize the surgeon-technology learning time and ultimately ease

Bioprintability: Physiomechanical and Biological Requirements of Materials for 3D Bioprinting Processes

“…One main impediment in this method is that the applied extrusion pressure exposes the cells to a noticeable level of (shear) stress as they pass through the syringe and nozzle (needle) which can cause damages [ 23 , 25 , 27 ]. To limit this stress, the bioink must show less viscous behavior [ 28 ], but the risk of this is deformation, collapse, and pore closure which will in turn lower the fidelity and resolution [ 24 ].…”

A Robust, Tough and Multifunctional Polyurethane/Tannic Acid Hydrogel Fabricated by Physical-Chemical Dual Crosslinking

“…Hydrogels can absorb a large amount of water molecules but not be dissolved in water, because they possess hydrophilic segments in their 3D crosslinked network [1,2]. On account of their admirable swelling property and eco-friendliness, hydrogels are applied in many fields such as medicine [3,4], agriculture [5,6] and cosmetics [7], etc. However, it is still a big challenge to prepare hydrogels for load-bearing applications including sensors [8,9], structural biomaterials [10,11], and soft robotics [12][13][14], because commonly synthetic hydrogels possess low mechanical robustness, poor stretchability and toughness, which are derived from their inherent structural heterogeneity or absence of effective energy dissipation mechanism, restricting their scopes of practical application [15].…”

Natural hydrogels R&D process: technical and regulatory aspects for industrial implementation

“…The second reason is predicting non-Newtonian fluid parameters based on Newtonian models. Although in vivo performance is always the ultimate metric for translation [32].…”

“…On the other hand, the hydrogel community often uses Herschel-Bulkley equation as a model that allows report hydrogel rheological properties for comparison. This equation simplifies the complex rheological parameters and their interactions [32]. Hydrogel clinical implementation needs a rheological study which is crucial and often overlooked, especially in 3D printing design.…”

“…Hydrogel precursor can easily flow through a needle gauge depending on its diameter. Here, it is possible to difference its final application: an injectable material (flowing through a needle, smaller diameter than a syringe) could have applications in laparoscopic surgery, whereas syringeable material may need open surgery for placement [32].…”