Jacob A. Orkwis

Severe peripheral nervous system injuries currently hold limited therapeutic solutions. Existing clinical techniques such as autografts, allografts, and newer nerve guidance conduits have shown variable outcomes in functional recovery, adverse immune responses, and in some cases low or minimal availability. This can be attributed in part to the lack of chemical, physical, and electrical cues directing both nerve guidance and regeneration. To address this pressing clinical issue, electrospun nanofibers and microfibers composed of piezoelectric polyvinylidene flouride‐triflouroethylene (PVDF‐TrFE) have been introduced as an alternative template for tissue engineered biomaterials, specifically as it pertains to their relevance in soft tissue and nerve repair. Here, biocompatible scaffolds of PVDF‐TrFE are fabricated and their ability to generate an electrical response to mechanical deformations and produce a suitable regenerative microenvironment is examined. It is determined that 20% (w/v) PVDF‐TrFE in (6:4) dimethyl formamide (DMF):acetone solvent maintains a desirable piezoelectric coefficient and the proper physical and electrical characteristics for tissue regeneration. Further, it is concluded that scaffolds of varying thickness promoted the adhesion and alignment of Schwann cells and fibroblasts. This work offers a prelude to further advancements in nanofibrous technology and a promising outlook for alternative, autologous remedies to peripheral nerve damage.

Peripheral nerve injuries require a complex set of signals from cells, macrophages, and the extracellular matrix (ECM) to induce regeneration across injury sites and achieve functional recovery. Schwann cells (SCs), the major glial cell in the peripheral nervous system (PNS), are critical to nerve regeneration due to their inherent capacity for altering phenotype post‐injury to facilitate wound healing. The ECM plays a vital role in wound healing as well as regulating cell phenotype during tissue repair. To examine the underlying mechanisms between the ECM and SCs, this work sought to determine how specific ECM cues regulate the phenotype of SCs. To address this, SCs were cultured on polydimethylsiloxane substrates of a variable Young's modulus coated with ECM proteins. Cells were analyzed for spreading area, proliferation, cell and nuclear shape, and c‐Jun expression. It was found that substrates with a stiffness of 8.67 kPa coated with laminin promoted the highest expression of c‐Jun, a marker signifying a “regenerative” SC. Microcontact printed, cell adhesive areas were then utilized to precisely control the geometry and spreading of SCs and by controlling spreading area and cellular elongation, expression of c‐Jun was either promoted or downregulated. These results begin to address the significant interplay between ECM cues and phenotype of SCs, while offering a potential means to enhance PNS regeneration through cellular therapies.