3D-Printed Piezoelectric Porous Bioactive Scaffolds and Clinical Ultrasonic Stimulation Can Help in Enhanced Bone Regeneration

Abstract

This paper presents a comprehensive effort to develop and analyze first-of-its-kind design-specific and bioactive piezoelectric scaffolds for treating orthopedic defects. The study has three major highlights. First, this is one of the first studies that utilize extrusion-based 3D printing to develop design-specific macroporous piezoelectric scaffolds for treating bone defects. The scaffolds with controlled pore size and architecture were synthesized based on unique composite formulations containing polycaprolactone (PCL) and micron-sized barium titanate (BaTiO3) particles. Second, the bioactive PCL-BaTiO3 piezoelectric composite formulations were explicitly developed in the form of uniform diameter filaments, which served as feedstock material for the fused filament fabrication (FFF)-based 3D printing. A combined method comprising solvent casting and extrusion (melt-blending) was designed and deemed suitable to develop the high-quality PCL-BaTiO3 bioactive composite filaments for 3D printing. Third, clinical ultrasonic stimulation (US) was used to stimulate the piezoelectric effect, i.e., create stress on the PCL-BaTiO3 scaffolds to generate electrical fields. Subsequently, we analyzed the impact of scaffold-generated piezoelectric stimulation on MC3T3 pre-osteoblast behavior. Our results confirmed that FFF could form high-resolution, macroporous piezoelectric scaffolds, and the poled PCL-BaTiO3 composites resulted in the d33 coefficient in the range of 1.2–2.6 pC/N, which is proven suitable for osteogenesis. In vitro results revealed that the scaffolds with a mean pore size of 320 µm resulted in the highest pre-osteoblast growth kinetics. While 1 Hz US resulted in enhanced pre-osteoblast adhesion, proliferation, and spreading, 3 Hz US benefited osteoblast differentiation by upregulating important osteogenic markers. This study proves that 3D-printed bioactive piezoelectric scaffolds coupled with US are promising to expedite bone regeneration in orthopedic defects.

Electrochemical Devices in Cutaneous Wound Healing

“…Few device-attributable problems or adverse effects have been recorded, showing that the treatment is both safe and simple. An interesting direction for further research is improving bone healing in oral implantology [ 98 ]. Specifically, this may aid with tilted implants in diabetic patients by diminishing microbial contamination around the oral cavity [ 98 , 99 ].…”

Biological properties of polycaprolactone and barium titanate composite in biomedical applications

“…PCL is a biodegradable polymer widely employed in implantable biomaterials. 130,131 The PCL-BT composites' d 33 piezoelectric coefficient increased as the amount of BaTiO 3 increased. Significantly, as compared to the unmodified PCL specimen, the BaTiO 3 inclusion up to 25 vol.% steadily improved the piezoelectric response to 1.2 pC/N; more specifically, the PCL-45BT and PCL-65BT specimens showed an improvement in the piezoelectric response of 2.4 and 2.6 pC/N, respectively.…”

“…As a result, the electrical stimulation (caused by the piezoelectric effect) from the PCL-BT scaffolds activated the calcium-sensing receptors, started the electrically sensitive Ca 2+ signal transduction and increased the Ca 2+ influx into MC3T3-E1 cells. 14,130 Ibrahim et al 137 explained that adding 36% of BT to 18% of PCL improved the wettability performance of the composite coating on CpTi and Ti3Nb13Zr alloys. Improving the wettability property increases the performance of the composite in osseointegration.…”

3D/4D printed bio-piezoelectric smart scaffolds for next-generation bone tissue engineering

“…The FDM-printed composite scaffolds showed a good distribution of HAp and BT fillers, resulting in a d 33 value close to the human bone (figures 4(d) and (e)). Sikder et al [92] developed high-quality bioactive PCL-BT filaments and FDM-printed These FDM-printed design-specific piezoelectric and regenerative scaffolds have broad application prospects in maxillofacial, cranial, and dental restoration and regeneration. Similar to DIW, FDM technology enables the multi-feedstock structure printability by integrating multiple nozzles, especially when combined with a flexible multi-axis manipulator, FDM can further realize the free forming of random surfaces.…”