(4fy) Biodegradable Nanofiber Bone-Tissue Scaffold As Remotely-Controlled and Self-Powered Electrical Stimulator
AIChE Annual Meeting
2021
2021 Annual Meeting
Meet the Candidates Poster Sessions
Meet the Faculty and Post-Doc Candidates Poster Session
Sunday, November 7, 2021 - 1:00pm to 3:00pm
Research Interests:
Biodegradable piezoelectric nanofibers
Ultrasound
Electrical stimulation
Bone regeneration
Tissue engineering
Introduction: Reconstruction of large bone fractures and defects remains a big challenge in orthopedic surgery. Regenerative engineering strategies, employing a combination of biomaterial scaffolds, stem/osteogenic cells and growth factors/small molecules, has emerged as an important area to create artificial engineering bone grafts. Although bone growth factors and small molecules are powerful, many of their toxic side-effects demand for a new approach to stimulate bone growth. Electrical stimulation (ES) is an excellent alternative and many electrical stimulators have been used to treat bone fractures. However, the electrical devices still struggle with limitations; while external stimulators are not very effective, implanted devices rely on toxic and non-degradable batteries, requiring invasive removal surgery. Piezoelectric materials, a group of “smart†materials which can generate electricity under applied force, might offer compelling battery-less stimulators to electrically stimulate bone growth. Bone is also piezoelectric in nature. Under deformation, bone generates surface charge, which drives the tissue to grow against the applied force. A piezoelectric scaffold can therefore mimic natural bone in receiving mechanical loading to induce bone growth and regeneration. Here we present for the first time a novel biodegradable and biocompatible scaffold of piezoelectric polymer of PLLA (Poly-L-lactide), which will be seeded with stem cells and subjected to acoustic pressure from ultrasound, to generate useful electrical charge for enhanced bone regeneration
Materials and Methods: We employ a powerful piezoelectric PLLA film1, 2 and seed the film with stem cells to construct a bone-piezoelectric scaffold. The scaffold is then subjected to ultrasound (US) to generate useful surface charge which consequently enhance significantly bone regeneration. Using cell based assays, we assess osteogenesis of the stem cells, seeded on the piezoelectric scaffold under applied ultrasound in vitro. In vivo experiment was also performed to show that the scaffold implanted inside a calvarial defect of mice and under applied noninvasive ultrasound (US).
Results and Discussion: Through mineralization ALP assay, Alizarin red assay, and qPCR to quantify expressions of osteogenic genes, we found a significant increase of osteogenic differentiation of the stem cells, cultured on piezoelectric scaffold under applied US (Figs. 1a-1e). In vivo experiment also shows an enhanced bone formation on the implanted piezoelectric scaffold (data not shown), subjected to the external US (Figs. 1f-1h). These experimental data show a clear effect of piezoelectric surface charge to induce bone regeneration.
Conclusions: Our piezoelectric material is biodegradable, which is a critical property for tissue scaffold and has not been achieved by any other reported piezoelectric materials. The presented piezoelectric PLLA material therefore offers a significant and unique biodegradable scaffold, which is inherently a biodegradable and wirelessly-controlled electrical stimulator for bone and tissue regeneration.
Materials and Methods: We employ a powerful piezoelectric PLLA film1, 2 and seed the film with stem cells to construct a bone-piezoelectric scaffold. The scaffold is then subjected to ultrasound (US) to generate useful surface charge which consequently enhance significantly bone regeneration. Using cell based assays, we assess osteogenesis of the stem cells, seeded on the piezoelectric scaffold under applied ultrasound in vitro. In vivo experiment was also performed to show that the scaffold implanted inside a calvarial defect of mice and under applied noninvasive ultrasound (US).
Results and Discussion: Through mineralization ALP assay, Alizarin red assay, and qPCR to quantify expressions of osteogenic genes, we found a significant increase of osteogenic differentiation of the stem cells, cultured on piezoelectric scaffold under applied US (Figs. 1a-1e). In vivo experiment also shows an enhanced bone formation on the implanted piezoelectric scaffold (data not shown), subjected to the external US (Figs. 1f-1h). These experimental data show a clear effect of piezoelectric surface charge to induce bone regeneration.
Conclusions: Our piezoelectric material is biodegradable, which is a critical property for tissue scaffold and has not been achieved by any other reported piezoelectric materials. The presented piezoelectric PLLA material therefore offers a significant and unique biodegradable scaffold, which is inherently a biodegradable and wirelessly-controlled electrical stimulator for bone and tissue regeneration.
References: 1. Curry, E. J. et al., PNAS 2018, 115, (5), 909-914. 2. Curry, E.J. et al., PNAS 2020, 117, (1), 214. 3. Das, R. et al., Nano Energy, 2020, 105208
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Figure 1. a. Schematics of in vitro experiment. b. ALP assay. c. Alizarin red assay. (d, e) qPCR gene expression to quantify osteogenic genes. Results obtained after 14 days of cell culturing. f. Schematic and image of in vivo implantation of the PLLA nanofiber scaffold into calvarial bone defect in vivo. (g, h) are representative images/histological slices of the mouse skull bone after 6 weeks of receiving the piezoelectric or non-piezoelectric PLLA with applied US. The staining and images show clearly a significant bone formation from the mice receiving the biodegradable piezoelectric nanofibers with applied US, compared to the control. *= 0.01, ** = 0.001, ***=0.0001. Student paired t-test.