Investigation of the 3D Printability of Covalently Cross-Linked Polypeptide-Based Hydrogels
Johnel Giliomee, Lisa C. du Toit, Bert Klumperman, and Yahya E. Choonara*
PUBLISHED IN: ACS Publications
ABSTRACT
The 3D printability of poly(l-lysine-ran–l-alanine) and four-arm poly(ethylene glycol) (P(KA)/4-PEG) hydrogels as 3D biomaterial inks was investigated using two approaches to develop P(KA)/4-PEG into 3D biomaterial inks. Only the “composite microgel” inks were 3D printable. In this approach, P(KA)/4-PEG hydrogels were processed into microparticles and incorporated into a polymer solution to produce a composite microgel paste. Polymer solutions composed of either 4-arm PEG-acrylate (4-PEG-Ac), chitosan (CS), or poly(vinyl alcohol) (PVA) were used as the matrix material for the composite paste. The three respective composite microgel inks displayed good 3D printability in terms of extrudability, layer-stacking ability, solidification mechanism, and 3D print fidelity. The biocompatibility of P(KA)/4-PEG hydrogels was retained in the 3D printed scaffolds, and the biofunctionality of bioinert 4-PEG and PVA hydrogels was enhanced. CS-P(KA)/4-PEG inks demonstrated excellent 3D printability and proved highly successful in printing scaffolds with a narrow strand diameter (∼200 μm) and narrow strand spacing (∼500 μm) while the integrity of the vertical and horizontal pores was maintained. Using different needle IDs and strand spacing, certain physical properties of the hydrogels could be tuned, while the 3D printed porosity was kept constant. This included the surface area to volume ratio, the macropore sizes, and the mechanical properties. The scaffolds demonstrated adequate adhesion and spreading of NIH 3T3 fibroblasts seeded on the scaffold surfaces for 4 days. Consequently, the scaffolds were considered suitable for potential applications in wound healing, as well as other soft tissue engineering applications. Apart from the contribution to new 3D biomaterial inks, this work also presented a new and facile method of processing covalently cross-linked hydrogels into 3D printed scaffolds. This could potentially “unlock” the 3D printability of biofunctional hydrogels, which are generally excluded from 3D printing applications.
Related Scientific Publications
Current treatments for glioblastoma (GBM) face challenges due to rapidly occurring tumor recurrences. In response, researchers have developed localized drug delivery systems, notably AT101-GlioMesh - an alginate-based mesh embedded with AT101-loaded PLGA microspheres. Fabricated for high encapsulation efficiency, this system ensures a sustained release of AT101, demonstrating a significant cytotoxic effect on GBM cell lines. This promising development could potentially revolutionize GBM therapy and prevent tumor recurrence.
Polysaccharide-based hydrogels offer great promise in 3D bioprinting due to their biocompatibility and cellular response, but their poor mechanical properties often require extensive crosslinking. The solution? Enter thermoresponsive bioinks. This study examines a triad of carboxymethyl cellulose, agarose, and gelatin as a potential thermoresponsive ink, demonstrating that specific blends can form stable hydrogels with desirable mechanical and physical properties. The bioinks' cytotoxicity was assessed on two cell lines according to ISO 10993-5 standards, and successful printing of complex 3D patterns confirmed their printability.
Dense collagen matrices, crafted through automated gel aspiration-ejection (GAE), offer exciting potential in the field of biofabrication. This study illuminates the crucial role fibrillization pH plays in both the real-time rheological changes during collagen hydrogel gelation and the properties of the resulting biofabricated matrices. Findings demonstrate a relative increase in hydrogel stiffness with higher gelation pH, with matrices demonstrating increased fibrillar density, alignment, and micro-compressive modulus at specific pH levels. Importantly, these matrices showed low cell mortality when seeded with fibroblasts. These findings may offer valuable insights applicable to other hydrogel systems and biofabrication techniques.
Understanding the biomechanical properties of arteries is complex due to their cylindrical shape and waveguide behavior. This study provides valuable insights by utilizing three-dimensional measurements on an artery-mimicking tube in water, categorizing the tube wall motion into transient and steady state responses. The study's approach enables a more accurate estimation of the motion and improves our understanding of wave propagation in arterial walls, presenting significant opportunities for enhanced measurement of arterial mechanical properties.
Researchers have devised a method called '3D wet writing' to create small-diameter arterial conduits. This technique uses ionic gelation for fabricating customizable constructs quickly and without a template. The constructs show mechanical properties similar to native blood vessels and demonstrate biocompatibility, indicating their potential use as vascular constructs.
User Cytocompatibility, biocompatibility, and biodegradability are amongst the most desirable qualities of wound dressings and can be tuned during the bioplatform fabrication steps to enhance wound healing capabilities. A three-stepped approach (partial-crosslinking, freeze-drying, and pulverisation) was employed in fabricating a particulate, partially crosslinked (PC), and transferulic acid (TFA)-loaded chitosan-alginate (CS-Alg) interpolymer complex (IPC) with enhanced wound healing capabilities.