Nanofiber-Hydrogel Composite with Human Adipose-Derived Stem Cells to Enable Soft Tissue Regeneration
Brian H. Cho, MD1,2, Xiaowei Li, Ph.D.2,3, Sashank Reddy, MD, Ph.D.1, Russell Martin, Ph.D.2,3, Michelle Seu, BA1,2, Gurjot Walia, BS1, Hai-Quan Mao, Ph.D.2,3, Justin M. Sacks, MD, MBA, FACS1.
1Department of Plastic and Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA, 2Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, USA, 3Department of Materials Science & Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
Develop a mechanically-tunable nanofiber-hydrogel composite to promote vascular ingrowth, survival, and migration of transplanted human adipose-derived stem cells (hASCs) for soft-tissue regeneration. This composite material directly addresses the limited utility of current soft-tissue repair paradigms, including fat grafting and dermal fillers, which are limited to small-volume defects and transient-volume restoration, respectively. METHODS:
We developed a unique composite scaffold by interfacially bonding biodegradable poly (caprolactone) fibers with hyaluronic acid hydrogel, forming an integrated structure resembling the architecture and mechanical properties of adipose tissue (Fig. 1A-1B). We optimized our composite for ability to promote hASC migration and vascularization in vitro. Using the optimized composite as a carrier, we subcutaneously delivered hASCs into rats to assess the effect of composite-mediated delivery on survival, adipose differentiation, and host-tissue integration of the transplanted cells. RESULTS: Human ASCs migrated the longest distance within the composite compared to soft and medium hydrogel controls (Fig. 1C-D; 203 vs. 122, and 0 µm; P<0.05). Within the soft hydrogel control and the composite, cultured ASCs exhibited vascular morphogenesis and organized to form multicellular tubular structures with branches and open luminal spaces. As shown in Fig. 1E, composite exhibited the highest network density (total length of interconnected branches divided by total area; Fig. 1F, 16.4 vs. 12.4, and 2.1 mm/mm2). In the rat model, we observed a significantly higher density of RECA-1+ endothelial cells within our composite compared with controls (Fig. 2). Additionally, composite-mediated hASC delivery yielded the highest degree of cell survival, spreading, and differentiation (Fig. 3).
Our composite scaffold promotes angiogenesis and enables delivery of hASCs and tissue regeneration for treatment of soft tissue defects. This composite scaffold has the potential for wide application to improve soft-tissue restoration in the clinical setting.
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