Traditional bone grafting procedures have consistently faced challenges such as donor site morbidity, bone regeneration limitations, availability, and cost. In contrast, 3D bio-printing offers a solution by facilitating the manufacture of biodegradable, drug-loaded osteoconductive scaffolds that promote osteogenesis, angiogenesis, and immunomodulation. Bioactive materials such as nano-hydroxyapatite, calcium phosphates, and mesoporous bioglass have demonstrated exceptional potential to enhance scaffold integration and accelerate bone regeneration. These materials serve as a foundation for developing advanced drug delivery platforms. To optimize therapeutic efficacy and achieve localized, sustained drug release at the injury site, pharmaceutical techniques including microencapsulation, nanoparticle-based delivery, and surface-functionalized systems have been employed. Further, a number of combinations of materials-technique are in Phase I-II clinical trials, and others, such as nano-hydroxyapatite are FDA-cleared or CE-marked, which is indicative of their established translational potential. Emerging advances in multi-material and 4D bioprinting are now being integrated with bioactive scaffolds to create responsive, drug-loaded constructs that adapt to the physiological environment. These innovations complement pharmaceutics-driven strategies by enhancing localized delivery and regenerative efficacy. Together, these innovations are reshaping the future of bone repair, and with appropriate material selection and improved manufacturing processes, 3D-printed bioactive scaffolds are poised to become a primary solution in orthopedic and maxillofacial regenerative medicine. The graphical abstract presents the bioactive materials used in 3D bioprinting for bone regeneration and their integration into composite bioinks. Natural polymers (e.g., alginate, GelMA, chitosan) provide extracellular matrix mimicking bioactivity and cell support, while synthetic polymers (e.g., PCL, PLGA, PLA) contribute mechanical strength, printability, and controlled degradation. Inorganic fillers, including hydroxyapatite (HA), β-tricalcium phosphate (β-TCP), bioactive glass, and nanosilicates (e.g., Laponite), impart osteoconductivity, mineral mimicry, and therapeutic ion release. These components are combined with cells and bioactive agents to generate 3D-printed scaffolds with controlled architecture and localized drug delivery for bone regeneration. 3D bioprinting produces personalized, drug-loaded bone repair scaffolds. Bioactive materials drive osteogenesis, angiogenesis, and integration. Hybrid polymer-ceramic inks offer strength, bioactivity, and control. Smart delivery systems enable sustained, localized therapeutic release. Phase 1–2 trials show strong translational potential for clinic use.
Wang et al. (Mon,) studied this question.