Three-dimensional nanofiber scaffolds with arrayed holes for engineering skin tissue constructs

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Biomaterials for 3D Cell Biology Research Letter

Three-dimensional nanofiber scaffolds with arrayed holes for engineering skin tissue constructs Lina Fu and Jingwei Xie, Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA Mark A. Carlson, Department of Surgery-General Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA Debra A. Reilly, Department of Surgery-Plastic Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA Address all correspondence to J. Xie at [email protected] (Received 20 April 2017; accepted 19 June 2017)

Abstract Three-dimensional (3D) scaffolds composed of poly(ε-caprolactone) and gelatin nanofibers were fabricated by a combination of electrospinning and modified gas-foaming. Arrayed holes throughout the scaffold were created using a punch under cryo conditions. The crosslinking with glutaraldehyde vapor improved the water stability of the scaffolds. Cell spheroids of green fluorescent protein-labeled human dermal fibroblasts were prepared and seeded into the holes. It was found that the fibroblasts adhered well on the surface of nanofibers and migrated into the scaffolds due to the porous structures. The 3D nanofiber scaffolds may hold great potential for engineering tissue constructs for various applications.

Introduction In the USA alone, chronic wounds affect 6.5 million patients and the associated cost for treating these wounds is about $25 billion each year.[1] Timely healing and closure is critical to reducing the cost and morbidity associated with chronic lower extremity wounds.[2] Debridement of the wound area and grafting with autologous split thickness grafts is still the gold standard for the treatment of chronic wounds.[3,4] However, the success rate of split thickness skin graft for healing chronic wounds is low in the range 33–73%.[5] Besides, meshed skin grafts usually require large areas of donor skin tissues for wound coverage due to their limited expansion ratios, which causes the potential risks of donor site morbidity and poor wound healing unique to the diabetic state.[6] Microskin grafts (e.g., autograft islands and stamp autografts) are often associated with low acceptance rates and the severe scarring.[7] In addition, the interstices of the grafts tend to form hypertrophic scarring. The ultimate goal of tissue engineering is to use a combination of cells/tissues, engineered materials, and suitable biochemical and physical cues to restore, maintain, or improve biologic functions of damaged tissues or organs.[8] Tissue engineered skin grafts may provide an optimized solution to improved healing of chronic wounds. Our previous studies demonstrated the fabrication of a “sandwich-type” nanofiberbased skin graft through seeding minced skin tissues onto the microwells of nanofiber membrane and covering with a radially aligned nanofiber membrane.[9] Although nanofiber membranes were able to direct cell migration and achieve the full

cell coverage on the surfac