Nanodiamonds/poly(vinylidene fluoride) composites for tissue engineering applications

Highlights

• Polymer composites with nanodiamonds were prepared for tissue engineering applications.

• Pristine and oxidized nanodiamonds were introduced within poly (vinylidene flouroide).

• Solvent casted porous composites crystallize in the electroactive γ-phase of PVDF.

• Nanodiamonds allow tuning the thermal and dielectric response of the polymer.

• The presence of nanodiamonds do not affect cell number and morphology.

Abstract

Poly (vinylidene fluoride) (PVDF) composites with different types of nanodiamond (ND) particles were produced by solvent casting. The variations of the morphological, structural, optical, thermal and electrical properties of the composites were studied as a function of nanofiller type (without and with air oxidation treatment) and concentration (in the range 0.1–1 wt%). No noticeable differences were found in the polymer crystallization process, the processing conditions and the filler determining the morphology and structure of the polymer. Nevertheless, ND nanofillers were useful for the tailoring of the optical properties, and also slightly contributed to the thermodynamic stability of the samples. An increase in the dielectric constant (∼2) of the ND composites, while maintaining constant the dielectric losses, was observed, independently of the filler concentration. On the other hand, solvent casted porous composites crystallize mainly in the electroactive γ-phase of PVDF. Those composite membranes were evaluated with pre-osteoblast culture tests and these revealed that the inclusion of ND nanoparticles does not induce cytotoxicity on the samples. Taking advantage of the properties of the polymer for cell culture and with the potential of the ND filler for protein functionalization and drug delivery, it is concluded that NDs/PVDF composites are a suitable platform for biomedical applications.

Introduction

The inclusion of nanomaterials in polymer matrices is an area of increasing interest, since it allows to introduce or tune specific characteristics of the materials such as mechanical, electrical, optical and thermal properties to reach specific application demands [1], [2], [3]. Polymer nanocomposites have been prepared with different nanofiller structures, such as nanoparticles, nanotubes and nanofibers, among others. Carbon fillers have demonstrated large interest due to their positive impact on the physical and chemical properties of the composites, such as electrical conductivity and mechanical properties, low density and ease of recycling [4], [5].

Nanoscale diamond particles, known as nanodiamonds (NDs), were first produced in the 1960s but only by the end of the 1990s became widely interesting for various purposes [6], [7]. NDs show excellent mechanical properties, high surface area and tunable surface structures, high thermal conductivity (up to 2000 W/m.K) and electrical resistivity, optical properties and fluorescence, chemical stability and resistance to harsh environments [7], [8], [9]. Hence, NDs have been proposed as fillers for high performance thermal interface materials and are promising to solve the challenge of increasing heat dissipation for electronic devices [2], [8]. They also show large grain boundary density and low to negative electron affinity, being therefore suitable for electronic applications. NDs can enhance the performance of electrochemically active polymers, improving their cycle stability, increasing their specific capacitance and capacitance retention at fast sweep rate [10], [11]. These nanoparticles present excellent optical properties due to their transparency in the visible region of the spectrum and high refraction index [12]. The presence of a nitrogen atom next to a vacancy, nitrogen–vacancy (NV) centers in nanodiamonds, leads to fluorescence properties. Fluorescent NDs combine the advantages of semiconductor quantum dots – small size, high photostability, bright multicolour fluorescence, with non-toxicity and biocompatibility, showing therefore large potential to develop in vitro and in vivo imaging applications. Furthermore, photoluminescent NDs present quantum yields, non-blinking, non-photobleaching characteristics and long luminescence lifetimes, making them advantageous among nanoparticles and dyes [7], [9].

The use of NDs as fillers in polymeric matrices leads to nanocomposites with superior mechanical, thermal and optical properties, which together with their biocompatibility and chemical stability make these materials excellent choices for the development of biomedical applications [12], [13]. Thus, NDs have an increasing impact in drug delivery, targeted cancer therapies, biosensor, anti-viral and antibacterial treatments, surgical implants and tissue engineering [7], [12]. The drug delivery feature for ND systems is accomplished by covalent attachment or physisorption of therapeutic substances. These mechanisms together with biocompatibility and the possibility of combination with imaging techniques confers NDs high potential for therapeutic treatment [9], [12], including breast cancer and liver cancer treatments [9], [13].

Furthermore, the ND properties in combination with the ability to deliver drugs and biologically active molecules are advantageous for the reinforcement of biodegradable polymers to create multifunctional tissue engineering scaffolds [12], [14]. NDs depict surface functionalization of scaffolds to promote tissue regeneration [15]. Octadecylamine (ODA) modified nanodiamond, poly (l-lactic acid) (ND-ODA-PLLA) composites were investigated for bone tissue engineering: PLLA is biocompatible and bioresorbable, but it is not mechanically robust for load bearing implants; the addition of ND-ODA leads to hardness and Young's modulus values that are close to those of human cortical bone [16], [17].

Electroactive polymer scaffolds based on piezoelectric polymers have been proposed for active tissue engineering approaches. These materials are characterized by providing an electrical response to a mechanical excitation or vice versa. Piezoelectricity can be found in living tissues, playing a significant role in several physiological phenomena. Piezoelectric polymers are often used to bone, neural and muscle regeneration [18]. Poly (vinylidene fluoride) (PVDF) is the most used piezoelectric polymer, due to its larger piezoelectric response, and provides an ideal material platform for proving the concept of mechano-electrical transductions for tissue engineering [18], [19]. Furthermore, PVDF is characterized by chemical resistance, suitable mechanical properties and hydrophobicity [20]. Thus, the incorporation of NDs within a PVDF matrix is a promising approach to produce composites with superior thermal, electrical, optical and biological properties.

The properties of NDs are influenced by the post-synthesis treatments to chemically modify the surface. The functionalization processes provide the incorporation of functional groups that are an intrinsic part of the NDs structure, influencing their thermodynamic stability compared to bulk diamond, controlling the agglomeration and removing impurities [7], [21], [22]. The main functional groups chemically bonded to the NDs surface are carboxyls (COOH), consisting of a carbon double bonded to oxygen and single bonded to a hydroxyl group (OH). Oxygen containing groups are already partially oxidized carbon, which produces less heat upon oxidation to CO₂ compared to unoxidized carbon, thereby stabilizing NDs and enabling their formation and persistence [23].

Other functional groups, such as amino, thiol and halogens can also functionalize the NDs surface. However, they require more complex procedures for the direct attachment on the diamond lattice. In these cases, the functional groups enable the immobilization of polymer chains, drug molecules, biomolecules or catalyst by simple adsorption of the functional unit or by directed covalent grafting [7]. NDs can be applied in biomedical or high performance materials, but demand a deep understanding and control of the surface properties of nanodiamond [21]. Furthermore, bacterial population proliferation can be controlled according to the reactive oxygen-containing surface groups on surfaces [24].

In this view, this work reports on the production of polymer composites based on PVDF using two types of ND nanoparticles and their morphological, structural, optical, thermal and electrical characterization. Furthermore, cell culture viability was studied with the use of pre-osteoblast cells.