A braided scaffold made from the tissue’s protein framework supported muscle regeneration after volumetric muscle loss in rats and beagles
A braided scaffold made from the tissue’s protein framework supported muscle regeneration after volumetric muscle loss in rats and beagles
On 29 August, the authors of a Nature Communications paper described a three-dimensional implant made from purified porcine intestinal submucosa. In rat and beagle models of volumetric muscle loss, it produced more new muscle fibers, blood vessels, and signs of nerve ingrowth than a dense control made from the same material.
An injury or surgery can remove more than one-fifth of a muscle’s mass, a condition known as volumetric muscle loss. For functional muscle tissue to grow within such a defect, cells, blood vessels, and nerve fibers must reach its center. The authors removed the cells from porcine intestinal submucosa. They cut the remaining extracellular matrix, which forms the tissue’s protein framework, into long strips, twisted them into threads, and braided these threads into a scaffold shaped to fill the defect.
For the control, the same purified material was arranged in dense layers. Pores accounted for 88.5% of the braided construct’s volume and 52.7% of the layered construct’s volume. The pores in the braided scaffold were interconnected in all directions. In the cell experiment, muscle cells had entered the braided scaffold by the first day, whereas they remained mainly around the edges of the layered scaffold. This difference showed that a scaffold’s internal structure affects how cells populate a large defect.
In rats, the researchers removed approximately half of one lower-leg muscle, the tibialis anterior. After eight weeks, the braided scaffold produced more muscle fibers and blood vessels, together with signs of nerve ingrowth. The muscle responded more strongly to electrical stimulation and generated greater force during a series of pulses than the muscle treated with the dense control. After two weeks, analysis of gene activity in individual cell nuclei showed more muscle fiber progenitor cells and more macrophages producing the protein IGF-1. Macrophages are immune cells that participate in tissue repair. When the researchers injected IGF-1 directly into the implantation site, the number of progenitor cells increased. The authors propose the following sequence: interconnected pores alter the composition of immune cells, and IGF-1 supports the growth of the progenitor cells that form muscle fibers.
The researchers then compared the scaffolds in six beagles. They removed a 4 × 2 × 2 centimeter section from the quadriceps, corresponding to 30–40% of its volume. After 16 weeks, the braided group had more blood vessels, muscle tissue, and signs of nerve ingrowth than the layered control group. In both models, the braided structure provided a route for cells, blood vessels, and nerve fibers to reach deep into the defect.