Formulation and characterization of a novel PHBV nanocomposite for bone defect filling and infection treatment

Biodegradable materials that combine bioactivity with sustained drug release have been proved promising for the treatment and prophylaxis of bone infection. In this work, injection-molded nanocomposites were formulated from poly(3-hydroxybutyrate-co-3-6%hydroxyvalerate) (PHBV), nanodiamond (nD) and nanohydroxyapatite (nHA) loaded with vancomycin (VC). The components were compounded using a rotary evaporator (PHBV/nHA/VC/nD-R) or a spray-dryer (PHBV/nHA/VC/nD-SD). The nanoparticles acted as a nucleating agent, increasing PHBV crystallinity from 57.1% to up to 73.3% (PHBV/nHA/VC/nD-SD). The nHA particles were found to be well distributed on the formulations fracture surface observed by SEM-EDS micrographs. PHBV/nHA/VC/nD-SD presented higher glass transition temperature (18.1 vs 14.8 °C) and stronger interface than PHBV/nHA/VC/nD-R, as determined by dynamic mechanical analysis (DMA). Furthermore, the incorporation of nanoparticles increased PHBV flexural elastic modulus by 34% and match the reported for human bone. Both systems were able to present a sustained release of VC for 22 days, reaching 7.1 ± 1.3%(PHBV/nHA/VC/nD-R) and 4.8 ± 0.6% (PHBV/nHA/VC/nD-SD). VC presented antibacterial activity even after being processed at 178 °C in an injection molding machine. Moreover, in vitro assays showed a good adhesion and growth of cells on the specimens and suggested a non-cytotoxic and non-cytostatic behavior. These findings indicate that these systems can be further explored as bone defect filling material.