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.

Carriers based on poly-3-hydroxyalkanoates containing nanomagnetite to trigger hormone release.

Poly-3-hydroxybutyrate (P(3HB)) and poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (P(3HB-co-3HHx)) are biocompatible and bioabsorbable biopolymers produced by different bacteria with potential for drug delivery in thermo-responsive magnetic microcarriers. Microparticles of P(3HB) and P(3HB-co-3HHx), with 5.85% mol of 3HHx, produced by Burkholderia sacchari, containing nanomagnetite (nM) and lipophilic hormone were prepared by simple emulsion (oil/water) technique leading to progesterone (Pg) encapsulation efficiency higher than 70% and magnetite loads of 3.1 and 2.3% (w/w) for P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg, respectively. These formulations were characterized by Infrared spectroscopy, X-ray diffraction, Thermal gravimetric analysis and Electron microscopy (TEM, SEM) techniques. The P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg microparticles presented spherical geometry with wrinkled surfaces and average size between 2 and 40 µm for 90% of the microparticles. The release profiles of the P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg formulations showed a hormone release trigger (6.9 and 11.1%, respectively) effect induced by oscillating external magnetic field (0.2 T), after 72 h. Progesterone release in non-magnetic tests with P(3HB-co-3HHx)/nM/Pg revealed a slight increment (5.6%) in relation to P(3HB)/nM/Pg. The experimental release of the P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg samples presented a good agreement with Higuchi model. The 3HHx comonomer content improves the hormone release of the P(3HB-co-3HHx)/nM/Pg formulation with potential for application to synchronize the estrous cycle.

Combining molecular and bioprocess techniques to produce poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) with controlled monomer composition by Burkholderia sacchari.

Biopolymers as polyhydroxyalkanoates (PHA) composed by different co-monomers 3-hydroxybutyrate and 3-hydroxyhexanoate [P(3HB-co-3HHx)] has attracted interest since its properties are similar to low density polyethylene. Burkholderia sacchari produces this copolymer with a very low 3HHx molar fraction, about 2 mol%. B. sacchari mutant (unable to produce polymer) was engineered to host PHA biosynthesis genes (phaPCJ) from Aeromonas sp. In addition, a two-step bioprocess to increase biopolymer production was developed. The combination of these techniques resulted in the production of P(3HB-co-3HHx) with 3HHx content up to 20 mol%. The PHA content was about 78% of dry biomass, resulting in PHA volumetric productivities around 0.45gl-1h-1. The P(3HB-co-3HHx) containing 20 mol% of 3HHx presented an elongation at brake of 945%, higher than reported before for this PHA composition. Here we have described an approach to increase 3HHx content into the copolymer, allowing the precise control of the 3HHx molar fractions.