Osteogenesis, hemocompatibility, and foreign body response of polyvinylidene difluoride-based composite reinforced with carbonaceous filler and higher volume of piezoelectric ceramic phase

Abstract

Hybrid polymer-ceramic composites have been widely investigated for bone tissue engineering applications. The incorporation of a large amount of inorganic phase, like barium titanate (BaTiO3) with good dispersion, in a polymeric matrix using a conventional processing approach has always been challenging. Also, the comprehensive study encompassing the interactions of key components of living organisms (cell, blood, tissue) with such hybrid composites is not well explored in many published studies. Built on our earlier studies and recognizing the importance of poly(vinylidene fluoride) (PVDF) as a widely used polymer for a wide spectrum of biomedical applications, the present study reports the qualitative and quantitative analysis of the biocompatibility of PVDF composite (PVDF/30BT/3MWCNT) reinforced with large amounts of BaTiO3 (30 wt %) and tailored addition of multiwalled carbon nanotubes (MWCNT; 3 wt %). The melt mixing-extrusion-compression moulding-based processing approach resulted in an enhancement of β-phase content, thermal stability, and wettability in the semi-crystalline PVDF composite. The enhanced hemocompatibility of PVDF/30BT/3MWCNT has been established conclusively by a series of in vitro blood-material interaction assays, including haemolysi, analysis of platelets attachment and activation, dynamic blood coagulation, and plasma recalcification time. The cytocompatibility study confirms an improved adhesion, proliferation, and migration of osteoprogenitor cells (preosteoblasts; MC3T3-E1) on PVDF/30BT/3MWCNT, in a manner better than neat PVDF, in vitro. When these cells were cultured in osteogenic differentiating media, the modulated osteogenesis, in terms of alkaline phosphatase activity, intracellular Ca2+ concentration, and calcium deposition on the PVDF/30BT/3MWCNT, was recorded. Following subcutaneous implantation of PVDF/30BT/3MWCNT in rat model, no apparent variation was recorded in the complete hemogram (blood hematology analysis) or serum biochemistry, post 30-, 60-, and 90-days surgery. Importantly, 90-days post-implantation, the fibrous capsule thickness was significantly reduced in the composites w.r.t PVDF alone, together with better blood vessel formation, indicating improved neovascularization around the composite. This study establishes the efficacy of inorganic fillers in enhancing the biocompatibility of PVDF, which could open up a wide range of biomedical applications.