Improved porosity of electrospun poly (Lactic-Co-Glycolic) scaffolds by sacrificial microparticles enhances cellular infiltration compared to sacrificial microfiber

Electrospinning is a technique used to fabricate nano-/microfiber scaffolds for tissue engineering applications. However, a major limitation of electrospun scaffolds is the high packing density of fibers that leads to poor cellular infiltration. Thus, incorporation of a water soluble sacrificial porogen, polyethylene oxide (PEO), was utilized to fine-tune the porous fraction of the scaffolds and decrease fiber packing density. Poly(lactic-co-glycolic) acid (PLGA) scaffolds were either co-electrospun with sacrificial PEO microfibers or co-electrosprayed with sacrificial PEO microparticles at three different extrusion rates to control the relative morphology and dose of PEO. A dose-dependent response in PLGA scaffold bulk porosity and pore area was noted as PEO content was increased. Notably, PLGA scaffolds after removal of sacrificial PEO microparticles significantly increased the porous fraction and pore area approximately 8, 10, and 14% and 46, 20, and 33 μm², respectively, relative to the analogous PEO microfiber scaffold. The tensile properties of the more porous PLGA scaffolds after PEO microparticle removal, remained stable for all extrusion rates of PEO tested, relative to the PLGA scaffolds after PEO microfiber removal. Histological analysis revealed that removal of PEO microparticles significantly increased the depth of cellular migration through the PLGA scaffolds, relative to PEO microfiber scaffolds, with maximum migratory depths of 1120 μm versus 150 μm over 28 days, respectively. Additionally, depth of cellular infiltration responded dose-dependently in the PEO microparticle scaffolds, whereas in the PEO microfiber scaffolds there was no correlation. Further analysis with Masson’s Trichrome staining and electron microscopy revealed that collagen density and depth of deposition substantially increased in PLGA scaffolds after removal of PEO microparticles relative to PEO microfibers. Thus, this study demonstrates an effective strategy to control the porous fraction of electrospun scaffolds via the incorporation of sacrificial PEO microparticles, without significant decreases in mechanical properties, thereby enhancing cellular infiltration and subsequent extracellular matrix deposition.