Poster O9 - Tailored bioactive fiber-reinforced printable hydrogel with tunable mechanical and osteogenic properties for bone repair

Introduction: Traditional bone grafting, which involves using the patient's own bone, presents drawbacks such as limited availability, surgical complexity, and donor site morbidity, leading to a search for alternative solutions. With over two million surgeries annually worldwide, bone grafting addresses a critical need, especially considering the statistics of bone fractures and disabilities caused by bone-related diseases. Personalized bone-regenerative materials, which include incorporating patient-derived cells, cytokines, antibodies, and biomarkers, have attracted significant attention in recent years. In this work, we introduce short microfiber-reinforced hydrogels with platelet-rich fibrin (PRF) to engineer implantable multi-material core-shell bone grafts.

Materials and

Methods: We employed 3D bioprinting technology to fabricate core-shell bone grafts using a hybrid composite of hydroxyapatite-coated poly(lactic acid) (PLA) fibers reinforced methacryolyl gelatin (GelMA)/Alginate hydrogel. The bioink is characterized with scanning electron microscope and rheometer for their morphological and mechanical properties. Further, in vitro cell culture studies were performed using HDF and MC3T3 cells and to determine their biocompatibility and bone formation.

Results, Conclusions, and Discussions: We prepared and optimized personalized bioinks composed of GelMA (7% to 10%), alginate (1% to 3%), and PLA microfiber (8 mg/mL to 35 mg/mL) for their printability and injectability, with optimal gelation time and viscosity for cell encapsulation. HA nanoparticles, a key component of natural bone, are coated onto short PLA microfibers to enhance the mechanical strength of the hydrogel formulation as well as induce cell differentiation. A significant stiffness enhancement was obtained when the microfibers are included to the bioink. As an implantable construct, 3D bioprinted cell-laden structures with a core-shell design are 3D bioprinted, where the shell is a hard material with HA-coated PLA microfibers and the core consists of a mixture of PLA microfibers PRF in hydrogel system. Incorporating the growth factors existing in PRF in the scaffold using polymeric fibers shows enhanced osteogenesis properties with sustained release compared to both structures without PRF and the structures with PRF without fibers. The constructs with the PRF mixed with fibers in the core showed better osteogenesis properties.

Conclusion: This study focused on creating biocompatible and osteoconductive constructs using GelMA-based hydrogels. By adjusting the rheological properties, these hydrogels become suitable for printing and injecting, with optimal gelation time and viscosity for cell encapsulation and bone repair. Adding HA nanoparticles to PLA microfibers strengthens the hydrogel, mimicking natural bone. The 3D bioprinted structures feature a core-shell design, combining a hard shell with coated microfibers and a core containing microfibers mixed with patient-specific PRF for sustained growth factor release. This method offers precise control over implant location, geometry, and material, tailoring implants to individual needs for more efficient bone regeneration. This scalable, reproducible, and cost-effective technology promises personalized bone implants for improved patient outcomes.

Acknowledgements (Optional): The authors acknowledge Mitacs and Ability Concept Inc., and Terasaki Institute for Biomedical Innovation for the funding support.