Composite-Mediated Angiogenesis for Soft Tissue Regeneration in a Large Animal Defect Model
Michelle Seu, B.A., Xiaowei Li, Ph.D., Zhengbing Zhou, M.D., Russell Martin, Ph.D., Kevin Colbert, M.S., Chi Zhang, B.S., Hai-Quan Mao, Ph.D., Justin Sacks, M.D., M.B.A..
Johns Hopkins School of Medicine, Baltimore, MD, USA.
PURPOSE: Soft tissue defects from aging, trauma, or congenital malformation affect millions of people each year. Existing options for soft tissue restoration have significant drawbacks: autologous flaps cause donor-site defects; prosthetics are prone to foreign-body response; and fat grafting and dermal fillers are limited to small volume defects and provide transient volume restoration. To address these limitations, we developed a nanofiber-hydrogel composite to promote angiogenesis and cellular infiltration for soft-tissue regeneration, specifically in a large defect.
METHODS: We have developed a novel composite scaffold resembling the architecture and mechanical properties of adipose tissue by interfacial bonding of biodegradable poly (caprolactone) fibers with hyaluronic acid. To examine the superior ability of our composite for soft tissue regeneration, we aim to create a large soft tissue defect model within the inguinal fat pads of female New Zealand White rabbits. Histology, immunohistochemistry, and bromodeoxyuridine (BrdU) assay were performed to investigate the ability of our composite to regenerate soft tissue in this large defect model.
RESULTS: We previously demonstrated robust angiogenesis and host cell infiltration within our composite after subcutaneous injection into Lewis rats (Fig.1). We successfully developed a large soft tissue defect model by designing standardized lesions in the rabbit inguinal fat pad (Fig.2). At post-operation day (POD) 7, we found that a large number of macrophages infiltrated our composite (Fig.3), many of which were polarized toward the M2 or “pro-healing” macrophage phenotypes; such macrophages could promote the vascular ingrowth at later timepoints. Now, using our novel inguinal fat pad model, we are testing the long-term effects of our composite for soft tissue regeneration.
CONCLUSION: We have demonstrated that our composite can facilitate blood vessel ingrowth and cellular infiltration 1 week after injection into a large soft tissue defect. Our nanofiber hydrogel composite represents a potential solution for soft-tissue reconstruction in the setting of acquired or congenital soft-tissue defects obviating the need for donor site morbidity.
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