Polyhydroxyalkanoates in Bone Alloplastic Materials: State of the Art and Future Perspectives.

Polyhydroxyalkanoates (PHAs) are bio-based, biodegradable polyesters increasingly explored as sustainable biomaterials for regenerative medicine. This review summarizes recent advances in PHA-based bone substitute materials, highlighting their properties, fabrication methods, and biological performance. PHAs combine biocompatibility, tunable mechanical behavior, and degradation into non-toxic metabolites, while copolymerization and monomer selection modulate the stiffness, crystallinity, and resorption rate. Processing techniques such as solvent casting, electrospinning, and additive manufacturing allow the production of porous architectures that mimic bone extracellular matrix. Electrospinning is particularly suitable for nanoscale fibrous matrices, whereas 3D printing enables patient-specific scaffolds with controlled geometry and interconnected porosity. Scaffold performance can be further improved through the incorporation of osteoconductive fillers, including hydroxyapatite, β-tricalcium phosphate, bioactive glasses, graphene oxide, and carbon nanotubes, as well as through drug-delivery and pro-angiogenic functionalization. In vitro and in vivo studies consistently report favorable cytocompatibility, enhanced osteogenic differentiation, vascularization, and effective repair of bone defects in animal models. However, clinical translation remains limited by production costs, variability in polymer quality, thermal processing constraints, and regulatory challenges. Future progress will rely on more efficient biosynthesis, medical-grade purification, multifunctional scaffold design, and stronger collaboration between academia, industry, and clinicians to unlock the full potential of PHAs in regenerative bone therapies.