Bioinspired Processing: Complex Coacervates as Versatile Inks for 3D Bioprinting.

3D bioprinting is a powerful fabrication technique in biomedical engineering, which is currently limited by the number of available materials that meet all physicochemical and cytocompatibility requirements for biomaterial inks. Inspired by the key role of coacervation in the extrusion and spinning of many natural materials, hyaluronic acid-chitosan complex coacervates are proposed here as tunable biomaterial inks. Complex coacervates are obtained through an associative liquid-liquid phase separation driven by electrostatic attraction between oppositely charged macromolecules. They offer bioactive properties and facile modulation of their mechanical properties through mild physicochemical changes in the environment, making them attractive for 3D bioprinting. Fine-tuning the salt concentration, pH, and molecular weight of the constituent polymers results in biomaterial inks that are printable in air and water. The biomaterial ink, initially a viscoelastic fluid, transitions into a viscoelastic solid upon printing due to dehydration (for printing in air) or due to a change in pH and ionic composition (for printing in solution). Consequently, scaffolds printed using the complex coacervate inks are stable without the need for post-printing processing. Fabricated cell culture scaffolds are cytocompatible and show long-term topological stability. These results pave the way to a new class of easy-to-handle tunable biomaterials for biofabrication.

3D printing of bio-instructive materials: Toward directing the cell.

Fabrication of functional scaffolds for tissue engineering and regenerative medicine applications requires material systems with precise control over cellular performance. 3D printing is a powerful technique to create highly complex and multicomponent structures with well-defined architecture and composition. In this review paper, we explore extrusion-based 3D printing methods (EBP, i.e., Near Field Electrospinning (NFES), Melt Electrowriting (MEW), Fused Deposition Modeling (FDM), and extrusion bioprinting) in terms of their ability to produce scaffolds with bio-instructive properties. These material systems provide spatio-temporal guidance for cells, allowing controlled tissue regeneration and maturation. Multiple physical and biochemical cues introduced to the EBP scaffolds are evaluated in their ability to direct cell alignment, proliferation, differentiation, specific ECM production, and tissue maturation. We indicate that the cues have different impacts depending on the material system, cell type used, or coexistence of multiple cues. Therefore, they must be carefully chosen based on the targeted application. We propose future directions in bio-instructive materials development, including such concepts as metamaterials, hybrid living materials, and 4D printing. The review gathers the knowledge essential for designing new materials with a controlled cellular response, fabrication of advanced engineered tissue, and developing a better understanding of cell biology, especially in response to the biomaterial.

Alginate based hydrogel inks for 3D bioprinting of engineered orthopedic tissues.

3D printed hydrogels have emerged as a novel tissue engineering and regeneration platform due to their ability to provide a suitable environment for cell growth. To obtain a well-defined scaffold with good post-printing shape fidelity, a proper hydrogel ink formulation plays a crucial role. In this regard, alginate has received booming interest owing to its biocompatibility, biodegradability, easy functionalization, and fast gelling behavior. Hence, this review highlights the significance of alginate-based hydrogel inks for fabricating 3D printed scaffolds for bone and cartilage regeneration. Herein, we discuss the fundamentals of direct extrusion 3D bioprinting method and provide a comprehensive overview of various alginate-based hydrogel ink formulations that have been used so far. We also summarize the requirements of hydrogel inks and 3D printed scaffolds to achieve similarity to the native tissue environment. Finally, we discuss the challenges, and research directions relevant for future clinical translation.