Natural macromolecule-based bioinks for 3D bioprinting: A systematic review of composition, physicochemical characterization, and biomedical applications

Three-dimensional (3D) bioprinting is an advanced technology that enables the precise fabrication of tissue-like structures using bioinks, offering advantages such as enhanced customization, scalability, and the potential to revolutionize fields like regenerative medicine, drug testing, and organ transplantation. This systematic review focuses on bioprinting techniques, particularly those used bioinks based on natural macromolecules (NMs) and their applications in biomedical fields. A comprehensive literature search was conducted across Scopus, PubMed Medline, and Embase, resulting in 193 identified studies, of which 86 met the inclusion criteria. Eligibility screening was performed using the software Rayyan. The findings revealed that extrusion-based bioprinting and the development of customized bioinks are prevalent in current research. NMs play a fundamental role in bioprinting due to their ability to mimic the extracellular matrix, enhancing cell adhesion and tissue integration. However, challenges such as variability in molecular properties and crosslinking efficiency highlight the need for standardized bioink characterization methods. Emerging trends in hybrid bioinks, which combine NMs with extracellular matrix components, show promising for applications in regenerative medicine, personalized therapies, and disease modeling.