Additive Manufacturing of Biomaterials: Integrated Translational Ecosystems, Process-Structure-Property Interactions and Emerging Paradigms for Next-Generation Biomedical Engineering.

Additive manufacturing (AM) has expanded the design space of biomaterials for biomedical engineering, enabling patient-specific geometries, controlled porosity, multi-material constructs and cell-compatible fabrication. However, clinical translation remains constrained by a mismatch between fabrication capability and biological, mechanical and regulatory performance. Unlike reviews focused on individual material families, isolated AM routes or specific applications, this review interprets AM of biomaterials as an integrated biomaterial-process-structure-property-translation ecosystem. It examines how material chemistry, feedstock state, printing route, architecture, post-processing and biological response jointly determine the reliability of acellular and cellular constructs, with particular emphasis on clinically relevant performance, reproducibility and long-term safety. Metallic, ceramic, polymeric, hydrogel-based and composite biomaterials are analysed alongside binder jetting (BJ), directed energy deposition (DED), material extrusion (ME) and jetting (MJ), powder bed fusion (PBF), VAT photopolymerisation and bioprinting. The review identifies recurring challenges across routes, including restricted material-process compatibility, limited prediction of process-structure-property relationships, post-processing-induced changes in biological performance, insufficient standardisation of printability and biofunctionality metrics, incomplete validation of cell-laden and vascularised constructs and weak transfer of laboratory protocols to clinically robust workflows. The main conclusion is that progress will depend less on expanding printable geometries alone and more on integrated optimisation of materials, processing windows, structural fidelity, biological validation, quality assurance and translational readiness. This ecosystem-level perspective provides a framework for evaluating limitations and defining future priorities in AM-based biomaterials for regenerative medicine, implants and precision biomedical engineering.