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​STM: A novel fully degradable scaffold can promote cartilage regeneration

​STM: A novel fully degradable scaffold can promote cartilage regeneration



 

​STM: A novel fully degradable scaffold can promote cartilage regeneration.


Osteoarthritis (OA) is one of the leading causes of pain and disability worldwide, affecting the lives of more than 300 million people worldwide [1].

In the United States, there are more than 32.5 million patients, and the annual cost of osteoarthritis per patient is estimated at $16,000 [2].

Surgical treatment of cartilage defects has traditionally focused on the use of transplanted replacement tissue grafts.

 

Despite its many advantages, alternative autografts and allografts have some disadvantages, including donor site morbidity (eg, pain and scarring), infection, immune responses (eg, allograft responses), and limited supply of transplanted tissue.

As an alternative, synthetic cartilage scaffolds have received considerable attention because there are no supply constraints and researchers can functionalize the scaffolds.

 

However, their widespread use has also been limited due to their inefficiency in generating hyaline cartilage after implantation.

Such grafts typically cannot bear weight in normal cartilage tissue and break down easily under repeated joint forces.

Therefore, it is necessary to seek a different method to effectively stimulate and accelerate the growth of cartilage.


Recently, the team of Professor Thanh D. Nguyen of the University of Connecticut published a research paper entitled Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits in Science Translational Medicine .

This study proposes a fully degradable scaffold based on the piezoelectric effect, which has a good effect of promoting chondrogenesis by controlling the polarization, charge amount and assembly of the scaffold.

In in vivo experiments, joint forces during exercise can be converted into electrical signals to stimulate and accelerate cartilage repair.

 

​STM: A novel fully degradable scaffold can promote cartilage regeneration

 

 

Piezoelectric materials deform when subjected to external forces and generate electrical charges on the surface. Bone and cartilage are inherently piezoelectric and respond to electrical stimulation. Previous research has shown that added electrical stimulation promotes bone and cartilage repair.

However, current devices for electrical stimulation, either through DC contact or capacitive coupling, have limitations, such as high infection rates, the potential for implant pain, and the stress associated with the surgical procedure, that prevent the widespread use of electrical stimulators. clinical.

When a non-invasive electrical stimulation device is applied to the knee joint, the externally generated electromagnetic field is greatly attenuated.

Devices implanted directly into the joint avoid the problem of tissue resorption. However, they often contain non-biodegradable materials and toxic batteries that must be removed through invasive procedures that can damage healing tissue.

Therefore, there is a need for a degradable implantable device that electrically stimulates tissues in the body, and is degraded and excreted by the body after completing its mission.

 


Based on the above inspiration, the researchers designed and fabricated a piezoelectric effect of L-polylactic acid (PLLA) film and assembled it into a three-dimensional scaffold.

The film is produced by electrospinning and will undergo natural polarization.

When subjected to external force, the upper surface (the surface facing the spinneret during electrospinning) has a net negative charge, and the lower surface (the surface that is attached to the collector during electrospinning) has a net negative charge. surface of the screen) has a net positive charge.

Previous studies have shown that negative charges have a more obvious repair effect on cartilage repair than positive charges. Therefore, the researchers controlled the scaffold structure to make it face cells and tissues with negative charges.

 

​STM: A novel fully degradable scaffold can promote cartilage regeneration

 


By analyzing the movement information of the New Zealand rabbits, the researchers determined that the pressure on the knee joints during walking was between 70 kPa and 600 kPa.

Based on this range, the researchers then seeded adipose-derived mesenchymal stem cells (ADSCs) on the surface of the piezoelectric scaffolds, applying pressures of 40 kPa, 80 kPa, or 160 kPa for 20 minutes per day.

After two weeks of cell differentiation, the surface cells of piezoelectric scaffolds significantly increased the expression of chondrogenesis-related genes COL2A1, ACAN and SOX-9.

Further research showed that the piezoelectric scaffold promoted the secretion of TGF-β1 in cells under the action of external force, which was also related to calcium ion channels.


In order to test the effect of the scaffold in vivo, the researchers used a critical cartilage defect model of the distal end of the femur in New Zealand rabbits, implanted the piezoelectric scaffold and observed the repair effect.

After a one-month rest post-operatively, the New Zealand rabbits were allowed to exercise (20 minutes per day) for one and two months.

The results showed that significant cartilage repair and subchondral bone repair occurred in the piezoelectric scaffold group at two months postoperatively (one month rest + one month exercise). In contrast, no similar repair effect was found in the sham-operated group, the non-piezoelectric stent group, and the piezoelectric stent group that did not exercise.

 

More specifically, in the piezoelectric scaffold group that underwent exercise, in addition to the well-formed cartilage layer, a large number of Safranin O-positive chondrocytes and GAGs were found in the deeper original defect area.

Since the implanted scaffold itself does not contain cells, it is speculated that the electric charges of the piezoelectric effect attract a large number of cells to aggregate and differentiate here, which promotes the repair of cartilage and bone in the entire defect area.

Further mechanical experiments showed that compared with the other control groups, the piezoelectric scaffold + exercise group obtained a repaired cartilage modulus that was closer to that of healthy cartilage after one month and two months of exercise.

 


To sum up, this research work proposes a new strategy based on piezoelectric effect, constructs a scaffold with efficient cartilage-promoting effect, achieves significant repair of New Zealand rabbit articular cartilage, and provides a direction for fully degradable tissue repair implants. 

 

 

 

 

 

 

references:

http://doi.org/10.1126/scitranslmed.abi7282
1 Boer, CG et al. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell 184, 4784-4818.e4717, doi: https://doi.org/10.1016/j.cell.2021.07.038 (2021).
2 Vaughn, IA, Terry, EL, Bartley, EJ, Schaefer, N. & Fillingim, RB Racial-ethnic differences in osteoarthritis pain and disability: a meta-analysis. The Journal of Pain 20, 629-644 (2019).

​STM: A novel fully degradable scaffold can promote cartilage regeneration

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