Investigation of cell infiltration and colonization in 3D porous scaffolds via integrated experimental and computational strategies

This study aimed to integrate experimental and computational methods to systematically investigate cell infiltration and colonization within porous scaffolds. Poly(lactic acid) discs (Diameter: 6 mm; Thickness: 500 µm) with open pores (Diameter: 400–1100 µm), corners (Angle: 30–120°) and gaps (Distance: 100–500 µm), and cellulosic scaffolds with irregular pores (Diameter: 50–300 µm) were situated in tissue culture plates and cultured with human dermal fibroblasts (HDFs). Both phase contrast and scanning electron microscopy revealed that HDFs initially proliferated on scaffold surfaces, then infiltrated into the porous structures via cell bridging and stacking strategies, which was affected by the initial cell seeding densities, porous structures and culture times. Based on the density-dependent cell growths in two-dimensional cell cultures, power law models were developed to quantitatively simulate cell growths on scaffold surfaces. Model analysis predicted the effect of cell seeding efficiency on cell infiltrations into the porous scaffolds, which was further validated via series cell seeding experiments. The novelty of this research lies in the incorporation of multiple experimental and computational strategies, which enables the mechanistic insights of cell invasion and colonization in porous scaffolds, also facilitates the development of suitable bioprocesses for cell seeding and tissue manufacturing in Tissue Engineering and Regenerative Medicine.