Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and amino-functionalized nanodiamond bionanocomposites for bone tissue defect repair.

Injection-molded nanocomposites of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) with 6 % of 3-hydroxyvalerate (HV) and amino-nanodiamonds (nD-A) were produced and characterized to investigate the effect of functionalized nanodiamonds on mechanical and biological behavior to bone replacement application. To prepare mixtures of PHBHV and nD-A in different concentrations, nD-A was dispersed in chloroform by sonication with 40 % of amplitude. Three specimens were characterized by infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (DRX), differential scanning calorimetry (DSC), 3-point flexural tests, dynamic mechanical analysis (DMA), and scanning electron microscopy (SEM). FTIR and TGA evidenced the existence of interactions between the nD-A and PHBHV. The crystallinity degree of PHBHV slightly reduced (~9 %) in nanocomposites and the morphology of the crystals changed. Nanocomposites achieved satisfactory dispersion and distribution of nD-A for low concentrations. Elastic modulus (E) increased from 1.96 ± 0.20 (PHBHV) to 2.59 ± 0.19 GPa (PHBHV/1.0%nD-A) (30 %). Despite the relatively limited dispersion, PHBHV/2.0 % nD-A had the best combination of E, strength, and maximum deformation. It had the highest glass transition temperature (43.1 vs 40.3 °C of PHBHV) and the best adhesion coefficient and reinforcement effectiveness. PHBHV-nD-A did not induce toxicity in 7 days and allowed cell fixation and expansion. These bionanocomposites should be considered for supplementary studies for bone tissue engineering.

A potential hybrid nanocomposite of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and fullerene for bone tissue regeneration and sustained drug release against bone infections.

Developing a multifunctional biomaterial for bone filling and local antibiotic therapy is a complex challenge for bone tissue engineering. Hybrid nanocomposites of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) with nanohydroxyapatite (nHA), fullerene (C60), and vancomycin (VC) were produced by injection. Fullerene was successfully impregnated with VC, as seen in FTIR. The crystallinity degree of PHBHV was slightly reduced in the presence of C60 and VC (64.3 versus 60.8 %), due to the plasticizing effect of these particles. It also resulted in a decrease in the glass transition temperature (Tg), observed by differential scanning calorimetry (DSC). Dense PHBHV/nHA/C60/VC had a flexural elastic modulus 29 % higher than PHBHV, as a result of the good interface between PHBHV, C60, and nHA - particles of high elastic modulus. Dense disks released 25.03 ± 4.27 % of VC for 14 days, which demonstrated its potential to be an alternative treatment to bone infections. Porous scaffolds of PHBHV/nHA/C60/VC were 3D printed with a porosity of 50 % and porous size of 467 ± 70 µm, and had compression elastic modulus of 0.022 GPa, being a promising material to trabecular bone replacement. The plasticizing effect of C60 improved the printability of the material. The hybrid nanocomposite was non-cytotoxic and showed good ability in adhering macrophage cells.

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 ±â€¯1.3%(PHBV/nHA/VC/nD-R) and 4.8 ±â€¯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.