D15 - Development of a Bioactive PVDF-TrFE Scaffold for Neural Tissue Engineering

Introduction: : Peripheral nerve injury (PNI) treatments often rely on grafts, but next-generation nerve guidance conduits (NGCs) offer promising biomaterial-based alternatives. Neural tissue engineering requires materials that actively influence cell behavior to promote repair. We developed production controls for polyvinylidene fluoride–trifluoroethylene (PVDF-TrFE), a piezoelectric copolymer capable of generating electrical stimuli noninvasively. To improve biointegration, we have incorporated decellularized extracellular matrix (dECM) proteins into PVDF-TrFE electrospun scaffolds. This study details fabrication parameters with scaffold properties, laying the groundwork for modeling how biophysical cues from materials influence neural tissue responses.

Materials and

Methods: : PVDF-TrFE scaffolds with varying dECM concentrations were electrospun under different solution formulations and process conditions. Viscosity was measured via viscometer; vapor pressure and dielectric constants were calculated from known thermophysical data. Scaffold properties—fiber morphology, protein incorporation, piezoelectric potential—were analyzed using SEM, AFM, contact angle, LC-MS, immunofluorescence, DNA quantification, FTIR, and XRD. These were correlated with fabrication inputs to identify control points for reproducible scaffold production. Dorsal root ganglion (DRG) explants and Schwann cells were cultured on scaffolds to assess integration, using MTT assays, immunohistochemistry, and single-cell RNA sequencing to evaluate cell phenotype and viability.

Results, Conclusions, and Discussions:: Viscosity increased as percentage of PVDF-TrFE and dECM increased, while vapor pressure and dielectric constant varied with solvent ratios, all influencing electrospinning. High-viscosity solutions required finer needles or faster feed rates for stable fiber formation. High dielectric constants reduced voltage thresholds for stable fiber formation; higher voltages yielded thinner fibers with greater β-phase content (Figure 2A). AFM revealed increased surface roughness with higher dECM content and vapor pressure (Figure 2B). EDS confirmed elevated carbon and oxygen with more dECM (Figure 2D). These properties informed piezoelectric coefficient estimates, supporting modeling of electrical responses to mechanical stimuli.
dECM was verified to be protein-rich and cell-free, minimizing immunogenicity. DRGs and Schwann cells cultured on scaffolds showed attachment and viability comparable to Matrigel controls (Figure 2C).
We established regression models (R² ≥ 0.7) predicting scaffold properties from fabrication inputs. This work defines material design rules for reproducible, functional neural scaffolds and sets the stage for biophysical simulations linking scaffold properties to neural regeneration. Additionally, we achieved higher dECM loading than prior studies, improving scaffold biofunctionality.
Altogether, this study defines critical production controls for creating complex, multifunctional scaffolds with enhanced reproducibility and performance in neural tissue engineering. These results provide a framework for future work linking scaffold properties to regenerative cell responses and advancing biophysical models of cell–material interactions.

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