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Abstract A new approach is described for fabricating 3D poly(ε‐caprolactone) (PCL)/gelatin (1:1) nanofiber aerogels with patterned macrochannels and anisotropic microchannels by freeze‐casting with 3D‐printed sacrificial templates. Single layer or multiple layers of macrochannels are formed through an inverse replica of 3D‐printed templates. Aligned microchannels formed by partially anisotropic freezing act as interconnected pores between templated macrochannels. The resulting macro‐/microchannels within nanofiber aerogels significantly increase preosteoblast infiltration in vitro. The conjugation of vascular endothelial growth factor (VEGF)‐mimicking QK peptide to PCL/gelatin/gelatin methacryloyl (1:0.5:0.5) nanofiber aerogels with patterned macrochannels promotes the formation of a microvascular network of seeded human microvascular endothelial cells. Moreover, nanofiber aerogels with patterned macrochannels and anisotropic microchannels show significantly enhanced cellular infiltration rates and host tissue integration compared to aerogels without macrochannels following subcutaneous implantation in rats. Taken together, this novel class of nanofiber aerogels holds great potential in biomedical applications including tissue repair and regeneration, wound healing, and 3D tissue/disease modeling. 

Abstract Chronic wounds are one of the most devastating complications of diabetes and are the leading cause of nontraumatic limb amputation. Despite the progress in identifying factors and promising in vitro results for the treatment of chronic wounds, their clinical translation is limited. Given the range of disruptive processes necessary for wound healing, different pharmacological agents are needed at different stages of tissue regeneration. This requires the development of wearable devices that can deliver agents to critical layers of the wound bed in a minimally invasive fashion. Here, for the first time, a programmable platform is engineered that is capable of actively delivering a variety of drugs with independent temporal profiles through miniaturized needles into deeper layers of the wound bed. The delivery of vascular endothelial growth factor (VEGF) through the miniaturized needle arrays demonstrates that, in addition to the selection of suitable therapeutics, the delivery method and their spatial distribution within the wound bed is equally important. Administration of VEGF to chronic dermal wounds of diabetic mice using the programmable platform shows a significant increase in wound closure, re‐epithelialization, angiogenesis, and hair growth when compared to standard topical delivery of therapeutics.