01-07 Glass for VML_1

[Image above] Bioactive glasses can effectively stimulate regeneration of tissue and bone—can they stimulate regeneration of muscle as well? Credit: Qiang Fu, Corning Incorporated

Prior to the 1970s, the goal of biomaterials was to replace, not repair, diseased or damaged tissues. But when Larry Hench discovered bioactive glass in 1969, that mindset changed—now, tissue regeneration and repair is the goal.

Bioactive glass is routinely used to regenerate and repair bone and hard tissues, and research on using bioactive glass to heal soft tissues continues to grow as well. Yet there is another application of bioactive glass that is rarely studied—muscle regeneration, specifically skeletal muscle.

Skeletal muscle is one of three major muscle types in the body. Also called voluntary muscle because of a person’s conscious control over its contraction and relaxation, skeletal muscles are attached to bones by tendons, and they produce all the movements of body parts in relation to each other.

Skeletal muscle can self-repair small wounds. However, critical-size injuries or volumetric muscle loss (VML) overwhelms muscle repair mechanisms and requires external help.

Current treatment options for VML, including physical therapy, removal of scar tissue, and muscle transposition, show limited success repairing damaged skeletal muscle. So researchers are actively searching for more effective methods to treat VML.

Biomaterials can stimulate bone and tissue regeneration, so it is no surprise that researchers are investigating using biomaterials to regenerate skeletal muscle as well. Yet soft materials such as hydrogel and decellularized extracellular matrix, materials known for their biocompatibility and easily controlled shape, are incapable of stimulating muscle regeneration when stem cells and/or growth factors are not incorporated in the soft materials.

It is possible to create soft materials containing stem cells and growth factors, but “the use of stem cells usually requires extra time/cost to culture them in vitro before transplantation and the growth factors are very expensive,” Qiang Fu, research associate at Corning Incorporated, explains in an email. “Furthermore, the process to deliver cells or growth factors is complicated and not well controlled.”

In contrast to soft materials, bioactive glasses are widely reported to stimulate growth of blood vessels and tissues without the need for stem cells or growth factors. However, few studies to date focus on muscle regeneration using bioactive glasses due to glass rigidity or brittleness and the lack of flexibility in shaping a glass scaffold.

In a new study by Fu and his colleagues at Corning (Aize Li, Huayun Deng, Carrie L. Hogue) in collaboration with professor John Mauro at The Pennsylvania State University (U.S.) and Weitao Jia, Haoran Hu, and Changqing Zhang at Shanghai Jiaotong University Affiliated Sixth People’s Hospital (China), they evaluate the ability of bioactive glasses to stimulate muscle regeneration—and their results are well worth the investigation.

“Here, we demonstrate for the first time that synthetic biomedical materials based on bioactive glasses of different degradation rates can be used to treat VML without using growth factors or stem cells,” they write in the paper.

The researchers evaluated three bioactive glass compositions (silicate 45S5, borate 13-93B3, and aluminoborate 8A3B) for skeletal muscle regeneration in two situations:

  1. In vitro—they observed how the glass compositions affected mouse muscle myoblast cells in solution
  2. In vivo—they injected the glass compositions into live rats

In solution, aluminoborate 8A3B demonstrated the highest potential of the three compositions. Specifically, “8A3B demonstrates a comparable weight loss to 45S5 while having the least impact on the pH of the soaking solution” and “8A3B glass with moderate boron release shows the most effectiveness in supporting in vitro angiogenesis [development of new blood vessels].”

In the rat model, aluminoborate 8A3B was again the leading contender—rats injected with 8A3B formed the highest number of new blood vessels and the largest new muscle fibers (about 20 μm compared to 5–10 μm with 13-93B3).

“The better ability of 8A3B composition than the rest suggests a desired boron release profile is important in promoting the formation of angiogenesis and stem cells, which agrees with literature studies on borate glasses,” the researchers conclude.

According to Fu, glass powder can be directly applied to the defect site during operation (no extra culture time needed), which is a big benefit in addition to its low cost. Credit: Qiang Fu, Corning Incorporated

Fu and Jia from the Sixth People’s Hospital plan to investigate long-term (up to six months) effects of bioactive glasses to restore functionality of regenerated muscle, and they also plan to investigate the glasses’ efficacy in a large animal model, such as rabbits or mini pigs.

Mauro adds that future studies will also continue to develop understanding of which aspects of glass composition govern muscle regeneration performance. “With such understanding, further optimization of the glass composition can be achieved to accelerate the regeneration of muscle tissue,” he says in an email.

The paper, published in Acta Biomaterialia, is “Glass-activated regeneration of volumetric muscle loss” (DOI: 10.1016/j.actbio.2019.12.007).

Update 01/07/2020 – All authors names added to the article