2023 AIChE Annual Meeting

The Impact of Fiber Inclusion on the Injectability of Shear-Thinning Hydrogels

Shear-thinning hydrogels change from a gel to a liquid state under high shear stress, such as the shear stresses that occur during injection [1]. Thus, these systems offer a non-invasive route for otherwise invasive treatments [1]. Shear-thinning hydrogels can be combined with other components to enable multi-functionality, including short fibers or particles [2]. For the inclusion of fibers, electrospinning has gained momentum as a simple technique to create fibrous structures that mimic the fibrous nature of the extracellular matrix [3]. Combining electrospun fibers within a shear-thinning hydrogel has the potential to provide cells with essential physical cues while retaining injectability [4]. For the inclusion of particles, hydrogel microparticles, also known as microgels, can be made from biocompatible, hydrophilic polymers [5]. Microgels are beneficial for inclusion due to their highly tunable size and structure, ability to encapsulate bioactive factors, and controllable composition and stiffness [5]. In the future, hydrogel composite systems including fibers and/or microgels can be manufactured using shear-thinning, guest-host hydrogels as an ideal multi-functional, injectable hydrogel for tissue repair applications. Studies manipulating the hydrogel, fiber, and/or microgel formulation, as well as the needle gauge are required to provide insight into the relationship between material properties, injectability, and biocompatibility, which is a prerequisite for clinical implementation. Thus arises the question: what is the effect of composite components on the shear stresses generated during injection of shear-thinning guest-host hydrogels?

JMPPro DOE was utilized to create a material-saving full-factorial design of experiments based on the independent variables (needle gauge, hydrogel weight percent, fiber length, fiber weight percent) and dependent variables (break force, glide force, and shear stress). For hydrogel synthesis, hyaluronic acid was modified with either cyclodextrin as the host functional group (Cd-HA), or adamantine as the guest functional group (Ad-HA) [6]. Regarding fiber synthesis, polycaprolactone was electrospun into an aligned fibrous mats and then cut into short fibers (20-60 um in length) using a cryotome [7]. To form hydrogel composites, fibers or were suspended in Cd-HA dissolved in PBS before being combined with Ad-HA within a syringe [10]. Then, a rheology strain sweep at 10 Hz from 0% to 500% strain was conducted to demonstrate the shear-thinning behavior of the guest-host hydrogel. Next, injection force testing was conducted to measure the break and glide forces for different hydrogel composite formulations and needle gauges. Using the iterative JMP Pro DOE software, significant independent variables were further analyzed and tested to determine trends.