(W1130-11-71) Characterization of 3D Printable Hydrogel-Inks for Cardiovascular Implants

Purpose: Three-dimensional (3D) printing provides fast and accurate fabrication of complex and high-quality products with improved reproducibility and ease of manufacturing. The printability of hydrogels into three-dimensional structures has been extensively explored in a variety of biomedical applications, such as tissue engineering, organ printing and cell-laden biological scaffold for regenerative medicine.
Novel biodegradable inks made of polymer complex (i.e., HEMA, Carbopol®, and EGDMA) could overcome the re-occurrence of long-term risks associated with the restrictive nature of permanent metallic cardiovascular implants. Biomimetic hydrogel inks produced through extrusion-based 3D printing would be biocompatible and biodegradable with sufficient mechanical strength that can withstand the dynamic cardiovascular environment.

Methods: Biodegradable implants were produced through pre-designed 3D models and printed through combination of 2-hydroxy ethyl methacrylate (HEMA), Carbopol® 974P NF polymer, and ethylene glycol dimethacrylate (EGDMA). The independent variables, such as composition of Carbopol and the amount of drug (Resveratrol) loaded in the cardiovascular implants, were optimized. The corresponding responses including rheological properties, thickness, mechanical strength and biodegradation profiles of cardiovascular implants were examined. Swelling ratios and degradation rates of the cardiovascular implants were tested in a 0.01 M PBS pH 7.4 at 37 ◦C for 72 hr, and the percentage volume change and fraction of remaining hydrogel, respectively, were examined. The compressive-strain cycle loads of 10, 20, 30, 40, and 50% were applied to 3D cardiovascular implants in a sequence of 5 cycles. The prototype of cardiovascular implants (9 mm diameter and 2 mm thickness) were compressed at a 1 mm/min speed with 225 N load cell. The stiffness (Young’s modulus) of the cardiovascular implants was obtained from stress vs. strain curves. One-way ANOVA was used to compare the means of independent samples, whereas Tukey’s HSD was used for a post-hoc analysis.

Results: The printing process was conducted at a speed of 2 mm/s with a layer height of 0.16 mm, 100% infill density. The 3D-printed cardiovascular implants were cross-linked using a 380 nm UV light (Anker® Bolder LC 40) of 27 mW/cm2 at a 3 cm distance for 60 min. After curing with UV radiation, the final form of the cardiovascular implants were obtained. The volume changes of 3D cardiovascular implants immersed in 0.01 M PBS at 37 C for 2 hr were displayed as 26.05 ± 3.09% and 20.5 ± 1.04% for pHEMA and pHEMA-Carbopol cardiovascular implants, respectively. The percentage fraction of weight remaining, and the degradation rates (Kd) after 21 days were determined to be 95.87 ± 0.50% and 0.30 ± 0.06 x 10-4/hr for pHEMA, respectively. The Young’s modulus of pHEMA cardiovascular implants decreased from 0.60 ± 0.01 × 10-2 MPa to 0.22 ± 0.01 × 10-2 MPa after 21 days. The optimization process, rheological studies and in-vitro cell toxicity studies of the customized cardiovascular implants were followed.

Conclusion: This study characterized combined polymer-based hydrogel with the aid of 3D printing. pHEMA was selected as a hydrogel base due to its biocompatibility and biodegradation properties. The addition of Carbopol has largely influenced the rheological properties and biodegradable behavior of polymer complex that could serve as a proof-of-concept to fabrication of biodegradable hydrogel and be further explored for customized cardiovascular implants, such as patch, scaffold and stent.

References: Veerubhotla, K, and Lee C.H. Design of Biodegradable 3D-Printed Cardiovascular Stent. Bioprinting. 2022; e00204.
Wang et al. 3D bioprinting in cardiac tissue engineering. Theranostics. 2021;11(16): 7948-7969.

Figure 1. Schematic illustration of a 3D-printed cardiac scaffold. (i) Carbopol loaded with pHEMA dispersed in the printing ink, (ii) a commercial 3D-printed, (iii) to print various scaffold designs, and (iv) a cardiac scaffold can be implanted onto the infarct zone of a heart that has suffered MI