Advancements in sustainable bioprinting: Materials, challenges and opportunities in transition from 3D to 4D printing

Bioprinting has emerged as a transformative technology in regenerative medicine, tissue engineering, and biomedical research by enabling the precise fabrication of biologically functional constructs. Recent developments have driven a paradigm shift from conventional three-dimensional (3D) bioprinting toward four-dimensional (4D) bioprinting, in which printed structures exhibit time-dependent shape morphing and stimuli-responsive behavior. This transition presents important opportunities for sustainable bioprinting through reduced material waste, incorporation of renewable and biocompatible bioinks and adaptive functionality in tissue models and implants. However, despite rapid progress, significant limitations persist, including the scarcity of eco-friendly and mechanically robust bioinks, energy-intensive fabrication processes, high production costs, scalability challenges, reproducibility issues and regulatory barriers that restrict clinical translation. This review critically analyzes the fundamental principles of 3D bioprinting and the evolution toward 4D bioprinting, with particular emphasis on recent advances in natural biomaterials, synthetic polymers and stimuli-responsive smart materials. Key biomedical applications tissue engineering, bone and musculoskeletal regeneration, wound healing, skin regeneration and organ regeneration and organ-on-a-chip systems are evaluated not only to highlight technological achievements but also to identify unresolved challenges and research gaps. Furthermore, the review discusses future directions for the field, emphasizing sustainable material development, hybrid fabrication strategies, standardized validation protocols and circular bio-manufacturing practices as essential enablers of translation. By aligning bioprinting technologies with sustainability and clinical feasibility requirements, this work provides a critical roadmap for advancing adaptive, patient-specific and environmentally responsible 3D and 4D bioprinting solutions.