Nanofiber-based tissue engineering scaffolds for repairing injured nerves and soft tissues
Martin, Russell Andrew
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One objective of the field of tissue engineering is to develop new biomaterials to unlock the body’s own potential to rebuild itself. Electrospun nanofibers are one such material, providing topographical features on the length-scales relevant for cellular interactions, recapitulating the cues from the native extracellular matrix. Nanofiber-based scaffolds require careful design to maximize fiber-cell interactions on the micron scale without sacrificing the porosity necessary for healthy healing responses. This thesis describes our work in developing electrospun nanofiber-based scaffolds for improved healing in peripheral nerve and soft tissue injuries. Peripheral nerve injuries pose a major health problem, leading to severe disability and poor quality of life. It is estimated that 5% of all open traumatic wounds are associated with peripheral nerve injuries, resulting in about 560,000 nerve repairs performed each year in the United States. Despite advancements in surgical techniques, functional recovery remains suboptimal. We have developed nanofiber-based nerve guides to provide off-the-shelf scaffolds for improving repairs in no-gap repairs, gap repairs, and ventral root avulsion repairs. We optimized the fiber properties through live-cell tracking and spheroid migration studies to maximize the contact guidance to Schwann cells, the key support cells of the peripheral nerve. We conducted extensive in vivo studies in rats, dogs, and rhesus macaques to determine the optimal design to maximize cell-fiber interactions without limiting porosity. Soft tissue losses from cancer surgery, trauma, aging, or congenital malformation affect millions of people each year. The loss of such tissues including skin, fat, fascia, and muscle can lead to major functional and aesthetic disturbances that are difficult to reconstruct with conventional methods. For example, more than 300,000 women a year undergo partial mastectomies for breast cancer in the United States, resulting in disfiguring deformities that go untreated in most cases. We have developed a novel scaffold for these injuries comprised of a composite between dispersed nanofibers and a hyaluronic acid hydrogel. These composites can match the stiffness of native fat while simultaneously retaining the porosity necessary for enhanced cellular infiltration and remodeling. We characterized the composite properties through extensive mechanical testing and demonstrated their efficacy through in vivo studies.