Development of natural polymer based composite scaffolds for Bone Tissue Engineering Applications

Traumatic or neoplastic bone defects remain a significant clinical challenge, as spontaneous healing is often incomplete and current treatments such as autografts, allografts, and metallic implants are limited by donor site morbidity, disease transmission risks, poor integration, and infection. Bone tissue engineering offers a promising alternative through the development of functional scaffolds. This work presents an integrated strategy for the design and fabrication of poly(3-hydroxybutyrate) [P(3HB)]-based composite scaffolds reinforced with graphene oxide (GO) for bone regeneration. The originality of the work lies in the use of medical-grade P(3HB) obtained using a specific Burkholderia sp. strain, its combination with a hydrophobic version of GO and its application in bone tissue engineering. In this work we optimised bioreactor fermentation conditions, achieving significantly enhanced yield (42.49 g/L) and productivity (1.52 g/L/h) as compared to other processes described in literature. This work involves a comprehensive, multi-scale approach that links processing, material properties, and biological performance. P(3HB) was selected for its biodegradability and mechanical suitability, while GO was incorporated to overcome its limited osteoinductivity, providing mechanical reinforcement, bioactivity, and antibacterial functionality. Composite films with varying GO concentrations demonstrated improved mechanical properties, mineralisation, osteogenic differentiation of primary human osteoblasts, and antibacterial activity against E. coli and S. aureus. An optimised composition (1 wt% GO) was further translated into three-dimensional scaffolds via melt-extrusion 3D printing and salt-leaching, achieving high structural fidelity, enhanced mechanical strength, porosity of the struts and improved cellular response.
Overall, this work advances current knowledge in the area of bone tissue engineering by integrating enhanced biopolymer production with scaffold design and biological validation, establishing a clear relationship between material composition, processing techniques, and functional performance. This work highlights the translational potential of P(3HB)/GO composites as multifunctional, antimicrobial, and osteogenic biomaterials for bone tissue engineering.