Functional Assessment of Skeletal Muscle Regeneration Utilizing Homologous Extracellular Matrix as Scaffolding

Abstract

The loss of a portion of skeletal muscle poses a unique challenge for the normal regeneration of muscle tissue. A transection injury with tissue loss will not heal due to the gap between muscle segments. A damage model was developed by removing a portion of the lateral gastrocnemius (GAS) of Sprague-Dawley rats. Maximal isometric, tetanic tension (P(o)) was measured after the removal of either a small defect (0.5 x 1.0 cm) or a large defect (1.0 x 1.0 cm) piece of the GAS. In situ P(o) immediately after creation of the defect was 88.3 +/- 2.0% of the nonoperated contralateral GAS force for small defect and 76.9 +/- 3.2% of control for large defect. No functional recovery occurred in either group over the course of 28 days. To enhance recovery, a homologous, decellularized, muscle extracellular matrix (ECM) was implanted into the 1 x 1 cm defect of the lateral GAS of Lewis rats. After 42 days, growth of blood vessels and myofibers into the ECM was apparent, but no restoration of P(o) occurred. These data demonstrate the ability of the ECM to support muscle and blood vessel regeneration, but full recovery of function does not occur after 42 days.

Trends in Mesenchymal Stem Cells' Applications for Skeletal Muscle Repair and Regeneration

“…Acquired muscle affections are seemingly more common in active humans, greatly associated to sports practice, but also quite frequent in other traumatic sceneries, such as road or workrelated accidents or war injuries [8][9][10][11]. Muscle damage can result from ischemia and denervation, to contusion, sprain damage, laceration, avulsion, and other severe tissue losses.…”

Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues

“…Similarly, other studies have indicated the possibility to use decellularized tissue scaffolds also for skeletal muscle repair and adipose-tissue engineering (L. Flynn et al, 2007;L.E. Flynn, 2010;Gillies et al, 2010;Merritt et al, 2010).…”

“…Several studies have shown that fibrin glue can provide sustained release of GFs during a few days to one week (Spicer & Mikos, 2010). Longer GF retention times can be achieved by modifications in the GF (Schmoekel et al, 2004), by integrating high GF-affinity moieties in the fibrin chains (Merritt et al, 2010), or by covalent linking of the GFs (Drinnan et al, 2010;Schmoekel et al, 2005). Examples of GFs that have been integrated in fibrin gels in skeletal tissue engineering applications include BMP-2 (Kang et al, 2011;Schmoekel et al, 2004;Schmoekel et al, 2005), TGF-1 and TGF-3 (Drinnan et al, 2010;W.…”

Therapeutic Potential of Adipose-Derived Stem Cells and Macrophages for Ischemic Skeletal Muscle Repair

“…Hematoxylin & eosin (H&E) staining was performed as previously described [28], and slides were observed with a light microscope (Nikon Diaphot, Nikon Corp., Tokyo, Japan) with the 20× objective lens. Images were taken using a mounted digital camera (Optronix Microfire; Optronix, CA, USA).…”

“…Calf muscles were surgically exposed and subjected to in situ functional measurements [28]. The Achilles tendon was tied to the muscle lever arm of a servomotor (model 305B, Cambridge Technologies) interfaced with a computer equipped with an A/D board (National Instruments).…”