While a lot of the body’s muscular tissue can regenerate well, serious injuries can result in volumetric muscle loss (VML), which greatly diminishes the muscle’s regeneration properties.
Current VML treatments comprise surgical interventions with muscle flaps or grafts along with physical therapy. However, surgical procedures often lead to reduced muscular function and, in some cases, the graft can fail.
Now, a team of researchers have devised a novel new protocol that could encourage artificial muscle regeneration.
The team comprises researchers from the Center for Nanomedicine within the Institute for Basic Science in South Korea and the Massachusetts Institute of Technology (MIT).
Researchers said they achieved effective treatment of VML in a mouse model by employing direct cell reprogramming technology in combination with a natural-synthetic hybrid scaffold.
Addressing the challenges
Inducing regeneration of skeletal muscle by integrating transplanted cells has been a promising strategy in the past. However, this comes with a number of challenges such as invasive muscle biopsies, poor cell availability, and limited long-term maintenance.
To address this problem, the research team used direct cell reprogramming, which allows the rapid generation of patient-specific target cells using autologous cells from the tissue biopsy.
This allowed the researchers to turn fibroblast cells, which are commonly found within connective tissues and often used in wound healing, into the induced myogenic progenitor cells needed for muscle tissue engineering.
Another challenge comes with the need to control the three-dimensional micro-environment at the injury site to ensure that the transplanted cells properly differentiate into muscle tissues with desirable structures.
While natural scaffolds exhibit high cell recognition and cell binding affinity, they fail to provide the robustness required for long-term mechanical support.
In contrast, a purely synthetic scaffold provides all the necessary physical and mechanical properties. However, these scaffolds are often hampered by a lack of cell recruitment and poor integration with the host tissue.
To combat this problem, the team bioengineered a hybrid muscle fibre structure that had both natural and synthetic properties.
Polycaprolactone (PCL) was chosen as a material for the fabrication of a porous scaffold due to its high biocompatibility. It was then completed through the incorporation of decellularised muscle extracellular matrix (MEM) hydrogel, a natural biomaterial that is widely used for the treatment of VML in clinical practice.
The study, published in Advanced Materials, said implantation of bioengineered muscle constructs in the VML mouse model not only promoted muscle regeneration, but also facilitated the functional recovery of damaged muscles.
Prof Cho Seung-Woo from the IBS Center for Nanomedicine, who led this study, said: “Further studies are required to elucidate the mechanisms of muscle regeneration by our hybrid constructs and to empower the clinical translation of cell-instructive delivery platforms.”
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