From Nature to Innovation: Exploring Natural Biopolymers in 3D Bioprinting for Bone Regeneration

Critical bone defects represent a global health challenge, necessitating specialized medical care and imposing significant costs on the public systems. In this context, many efforts in the tissue engineering and regenerative medicine framework have been made, focusing on developing biomaterials for bone regeneration. Additive manufacturing, known as 3D printing, has emerged as a promising technology for creating revolutionary biomedical devices. An advancement of this technique, 3D bioprinting, enables the fabrication of biomaterials intended for tissue regeneration and the transplantation of synthetic organs, using bioinks (cell-enriched hydrogels) and inks (hydrogels with or without bioactive agents) to produce a variety of devices, such as scaffolds, dressings, microneedles, and blood vessels. Thus, biopolymers have emerged as promising materials for the development of biomaterials and bioinks in tissue engineering because of their biocompatibility, biodegradability, low toxicity, and ability to mimic the extracellular matrix. Therefore, this review discusses recent advances in natural biopolymer-based bioinks for 3D bioprinting in bone regeneration, highlighting rheological properties, mechanical performance, biological functionality, and strategies such as chemical modification, nanomaterials, and smart systems. In addition, challenges related to vascularization, structural stability, immune responses, and clinical application are discussed.