Plastic Surgery Research Council
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DECELLULARIZED MUSCULOFASCIAL MATRIX FOR SOFT TISSUE REPAIR AND REGENERATION
Presenter: Joshua Johnson, MS
Co-Authors: Johnson JA; Wang LN; Chang DW; Zhang QX
The University of Texas MD Anderson Cancer Center

Scaffolds, providing structural support and interacting with cells and tissues, play the key role in the process of tissue engineering. This study aimed to develop decellularized musculofascial matrix (DMM) compatible with human adipose-derived stem cells (hASCs) delivery for soft tissue repair and regeneration. A novel decellularization protocol was developed to remove cell components from pig musculofascial tissues. Resultant DMM was separated to decellularized muscle (DM) and decellularized fascia (DF). hASCs were integrated with DMM to test DMM s biocompatibility in vitro. DMM was implanted subcutaneously in Fisher rats to evaluate DMM-induced immunoresponse and remodeling. DMM was then applied to repair muscle defect in a rat model. Further, DMM seeded with hASCs was used to repair ischemic wounds in the random flap of the rat. Negative H&E and DAPI staining and DNA quantification confirmed cell removal in DMM. DMM maintained natural extracellular matirx structure with nanofibrous features, strong mechanical properties, and biochemical compositions (collagen+, laminin+ and VEGF+; MHC1-). DMM provide a niche for hASCs adhesion and proliferation. hASCs maintain their stemness (Kcf4+, Oct4+ and Sox2+) and differentiation potential (adipogensis and osteogensis) on DMM. In-vivo animal tests demonstrated that DMM caused little immunoresponse when implanted subcutaneously (few CD4+ and CD8+; CD68+/CD163+/CD80-). However, DM and DF showed different characteristics in some aspects, such as that DM extraction showed stronger influence in promoting cell outgrowth and microvascular formation (Aortic ring assay). Muscle defect repair by DM indicated its myogenic regeneration capacity (MyoD1+ and CD31+). Further, hASCs seeded on DM significantly enhanced ischemic wound healing than control groups without implants. Increasd cell proliferation (BrdU+, Ki67+), angiogenesis (CD31+,VWF+), and reduced inflammation (MPO and COX2 staining) were found to associate with the effect of DM/ hASCs system on accelerating ischemic wound healing. In all, DMM provides a promising bio-scaffold for soft tissue engineering and regeneration.


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