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An Injectable Nanofiber Hydrogel Composite with Interfacial Bonding for Soft Tissue Filling and Augmentation
Georgia C. Yalanis, BS, MSc1, Russ Martin, BS2, Sashank Reddy, MD1, Jisuk Choi, PhD2, Denver M. Lough, MD1, Hai-Quan Mao, PhD2, Justin M. Sacks, MD1.
1Johns Hopkins University, Department of Plastic and Reconstructive Surgery, Baltimore, MD, USA, 2Johns Hopkins University, Whiting School of Engineering, Baltimore, MD, USA.

Background: Reconstruction of acquired or age-related soft tissue defects causes donor site morbidity, infection, and fibrosis. A superior approach using the body's regenerative capacity and an injectable scaffold would allow immediate restoration of form and permit native tissue regeneration. We developed a nanofiber-hydrogel composite with interfacial bonding to maintain 3D structure and promote soft tissue regeneration upon subcutaneous injection.
Methods: Electrospun PCL fibers grafted with poly-acrylic acid and surface-modified with maleimide groups were cryo-milled to disperse fibers inside a hyaluronic acid hydrogel to create nanofiber-hydrogel composites with interfacial bonding. Liquid composites congealed at RT, were injected into the inguinal fat pad of Lewis rats, explanted en bloc at 1-, 2-, and 4-week intervals, and fixed and stained.
Results: Composite morphology mimicked ECM composed of collagen and elastin with high porosity permitting ASC migration in vitro as nanofibers act as cellular guides similar to native cytoskeleton. Prior to explant composites were non-immunogenic, maintained 3D volume, and were incorporated into native fat. Histology demonstrated no cellular atypia or fibrosis and tissues demonstrated capillary formation, and fat regeneration.
Conclusion: We developed an injectable nanofiber-hydrogel composite that promotes cellular migration in vitro and in vivo and maintains 3D volume after injection while predictably degrading to facilitate native tissue ingrowth without foreign body encapsulation. Our injectable composite allows immediate filling and regeneration of soft tissues without the negative sequelae associated with implant-based devices, autologous transfers.

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