Researchers at the University of Connecticut developed an experimental biodegradable scaffold that uses externally applied ultrasound to generate electrical stimulation and promote bone regeneration.
The technology could eventually provide a new approach to treating large bone defects that are difficult to heal. However, the research was preclinical: the scientists tested the technology in cells and a mouse model, not in people (Das et al., 2020).
Key Takeaways
- UConn researchers developed a biodegradable poly(L-lactic acid), or PLLA, nanofiber scaffold for bone regeneration.
- The scaffold is piezoelectric, meaning mechanical stimulation can cause it to generate electrical charges.
- Applying ultrasound remotely activated the implanted scaffold without batteries or implanted electrical wiring.
- The system enhanced the osteogenic differentiation of stem cells in laboratory experiments.
- In mice, the ultrasound-activated scaffold promoted bone regeneration in a critical-sized skull defect.
- The technology remains experimental and has not been shown to accelerate fracture healing in human patients.
How Does the Ultrasound-Activated Bone Scaffold Work?
Bone tissue responds to mechanical and electrical signals, and researchers have long investigated electrical stimulation as a way to promote bone regeneration.
The UConn team sought to combine electrical stimulation with a tissue-engineering scaffold while avoiding implanted batteries, wires, and permanent electronic components.
Their solution was a nanofiber scaffold made from PLLA, a biodegradable polymer with piezoelectric properties (Das et al., 2020).
Bone Fracture
Piezoelectric materials generate electrical charge when subjected to mechanical stress. In this system, externally applied ultrasound provides that mechanical stimulation.
The acoustic pressure causes the PLLA nanofibers to generate controlled surface charges, providing localized electrical stimulation at the scaffold.
In effect, the implanted scaffold acts as a remotely controlled, self-powered electrical stimulator.
What Did the Study Find?
The researchers first tested the technology with stem cells in laboratory experiments. Ultrasound activation of the piezoelectric scaffold enhanced osteogenic differentiation, the process through which stem cells develop characteristics associated with bone-forming cells (Das et al., 2020).
The researchers then evaluated the approach in mice with a critical-sized calvarial defect, a skull-bone defect deliberately made large enough that spontaneous complete healing is difficult.
The combination of the PLLA scaffold and externally applied ultrasound promoted bone regeneration in this model (Das et al., 2020).
These findings provided proof of concept that ultrasound could remotely activate a biodegradable piezoelectric scaffold to deliver electrical stimulation for bone tissue engineering.
Why Could a Biodegradable Scaffold Be Useful?
A major advantage of the experimental system is that it does not require a battery or wired electrical connection to generate stimulation.
Instead, energy is supplied remotely through ultrasound.
PLLA is also biodegradable, meaning the scaffold is designed to gradually break down rather than function as permanent electronic hardware. This could potentially reduce the need to surgically retrieve a stimulation device after it has served its purpose.
The researchers proposed that combining biodegradability, tissue support, and remotely controlled electrical stimulation could make the technology useful for future regenerative-medicine applications (Das et al., 2020).
Does the Scaffold Heal Human Bone Fractures Faster?
That has not been established.
The study demonstrated enhanced bone-related cell differentiation in laboratory experiments and bone regeneration in a mouse skull-defect model. It did not test the scaffold in people and therefore cannot show that it shortens fracture-healing time in human patients.
A critical-sized skull defect in a mouse is also not equivalent to a typical broken arm, leg, or hip in a person.
Additional preclinical research would be required to evaluate factors such as long-term safety, degradation, optimal ultrasound exposure, effectiveness in different types of bone injuries, and performance in larger animal models before clinical use could be considered.
Human clinical trials would ultimately be necessary to determine whether the technology is safe and effective for patients.
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Final Thoughts
The UConn study demonstrated an innovative way to combine tissue engineering, ultrasound, and electrical stimulation.
By creating a biodegradable piezoelectric scaffold that can generate electrical charges when activated by externally applied ultrasound, researchers were able to enhance osteogenic differentiation in laboratory experiments and promote bone regeneration in a mouse model (Das et al., 2020).
The findings are promising for regenerative medicine, particularly because the experimental scaffold is biodegradable, battery-free, and remotely activated.
However, the technology remains preclinical. The study should therefore be viewed as proof-of-concept research rather than evidence of a new treatment that can already accelerate fracture healing in people.
Reference
Das, R., Curry, E. J., Le, T. T., Awale, G., Liu, Y., Li, S., Contreras, J., Bednarz, C., Millender, J., Xin, X., Rowe, D., Emadi, S., Lo, K. W.-H., & Nguyen, T. D. (2020). Biodegradable nanofiber bone-tissue scaffold as remotely-controlled and self-powering electrical stimulator. Nano Energy, 76, 105028. https://doi.org/10.1016/j.nanoen.2020.105028
