Description:

Mimi Wu Young, MD

Northwestern Resident

Background: Traumatic soft tissue injuries obtained on the battlefield can result in devastating functional, cosmetic, and psychosocial deficits. Muscle loss secondary to these injuries can present as a challenge to reconstruct, subsequently leading to poor restoration of function. Given its ability to heal in a regenerative manner, we evaluated the outcomes of decellularized fetal soft tissue matrix for skeletal muscle regeneration in a rat latissimus dorsi defect.
Methods: Composite soft tissue was harvested from the trunk of New Zealand White rabbit fetuses on gestational day 24 as well as Sprague-Dawley rats on gestational day 18 and neonatal day 3. These tissues underwent a negative pressure assisted decellularization process then were implanted into 1 cm diameter rat latissimus dorsi defects or left as a defect alone. Tissue harvest was carried out on post-operative day 60. Immunohistochemistry, qPCR, and western blot analysis were performed to characterize myogenesis, neovascularization, inflammation, and fibrosis within the explanted matrices and defects alone.
Results: Scanning electron microscopy and picrosirius red staining revealed a loose network of type III reticular collagen fibers which was unique to fetal scaffolds. Substantial ingrowth of myocytes was visualized in both types of fetal matrix with significantly larger quantities of myosin heavy chain on immunofluorescence signal intensity analysis as well as western blot analysis. A dense microvascular network was appreciated within the implanted matrices. At day 60, both markers of inflammation (IL1-β, TNF-α, TGF-β, Cox-2) and markers of fibrosis (CTGF, Col-1, α-SMA) were significantly decreased in fetal scaffolds. No difference in inflammatory markers was observed between allogeneic and xenogeneic scaffolds.
Conclusion: Decellularized xenogeneic fetal soft tissue matrix is a promising scaffold for muscle regeneration, demonstrating significant myocyte proliferation and supporting microvasculature while downregulating inflammation and fibrosis.