Abstract
In situ tissue engineering is a technology in which non-cellular biomaterial scaffolds are implanted in order to induce local regeneration of replaced or damaged tissues. Degradable synthetic electrospun scaffolds are a versatile and promising class of biomaterials for various in situ tissue engineering applications, such as cardiovascular replacements. Functional in situ tissue regeneration depends on the balance between endogenous neo-tissue formation and scaffold degradation. Both these processes are driven by macrophages. Upon invasion into a scaffold, macrophages secrete reactive oxygen species (ROS) and hydrolytic enzymes, contributing to oxidative and enzymatic biomaterial degradation, respectively. This study aims to elucidate the effect of scaffold microarchitecture, i.e., μm-range fiber diameter and fiber alignment, on early macrophage-driven scaffold degradation. Electrospun poly-ε-caprolactone-bisurea (PCL-BU) scaffolds with either 2 or 6 μm (Ø) isotropic or anisotropic fibers were seeded with THP-1 derived human macrophages and cultured in vitro for 4 or 8 days. Our results revealed that macroph age-induced oxidative degradation in particular was dependent on scaffold microarchitecture, with the highest level of ROS-induced lipid peroxidation, NADPH oxidase gene expression and degradation in the 6 μm Ø anisotropic group. Whereas, biochemically polarized macrophages demonstrated a phenotype-specific degradative potential, the observed differences in macrophage degradative potential instigated by the scaffold microarchitecture could not be attributed to either distinct M1 or M2 polarization. This suggests that the scaffold microarchitecture uniquely affects macrophage-driven degradation. These findings emphasize the importance of considering the scaffold microarchitecture in the design of scaffolds for in situ tissue engineering applications and the tailoring of degradation kinetics thereof.
Highlights
The use of electrospun degradable synthetic scaffolds is being explored for the repair or replacement of various load-bearing tissues
To relate possible differences in macrophage degradative behavior to scaffold-induced macrophage polarization, we investigated the polarization profiles of the macrophages cultured on the different scaffold microarchitectures, and compared the phenotypical profiles to those macrophages seeded in 6 μm isotropic scaffolds with the exogenous addition of cytokines to induce polarization into the M1, M2a, and M2c macrophage phenotypes
For the anisotropic scaffolds, the majority of the fibers were oriented in the circumferential direction of the electrospinning mandrel, while the isotropic scaffolds exhibited almost equal distributions in all directions (Figure 2B)
Summary
The use of electrospun degradable synthetic scaffolds is being explored for the repair or replacement of various load-bearing tissues (e.g., heart valve replacement, pelvic floor reconstruction; Kluin et al, 2017; Hympánová et al, 2018). Such scaffolds are designed with the aim to induce endogenous regeneration of the replaced tissue, directly in its functional site, a process known as in situ tissue engineering. The degradation kinetics of the implanted electrospun biomaterials represent a critical parameter for successful in situ tissue engineering
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