Macrophage-Driven Biomaterial Degradation Depends on Scaffold Microarchitecture

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.

Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction

“…This outside‐interior remodeling style emphasized central role of PCL nanofibrous interface, in mediating profound PVAT‐biomaterial interaction that leads to myogenic differentiation. Although physical structures, such as fiber diameter or fiber density influences M2 transition of macrophages, [ 45 ] both in vitro and in vivo results in this study revealed DTβ4 incorporation is determinant to M1/M2 ratio conversion. For the first time, we found that DTβ4 treated macrophages presented more autophagosomes, indicating enhanced autophagy of cells.…”

Macromechanics and polycaprolactone fiber organization drive macrophage polarization and regulate inflammatory activation of tendon in vitro and in vivo

“…Interestingly, nanofiber cues compared to micro-fiber cues have particular potential to alter fibroblast response from repair to healing [25]. Furthermore, it has been demonstrated that different inflammatory responses were elicited depending on biomaterial grating patterns or electrospun fibers of different thickness and compositions [50][51][52]. While the description of the underlying links between inflammatory mechanisms and tendon homeostasis is thus crucial to understand the factors that drive tissue repair quality [53], these links have been under-investigated.…”

Hemodynamic loads distinctively impact the secretory profile of biomaterial-activated macrophages – implications forin situvascular tissue engineering

“…1,54 Via paracrine signaling, M2 macrophages have been shown to stimulate fibroblast proliferation and subsequent collagen deposition, while a more pro-inflammatory M1 macrophage profile augments the tissue degradative potential. 5,14,[55][56][57] We assessed the paracrine effects of our dynamically cultured macrophages on scaffold-seeded (myo)fibroblasts and observed minor differences in the proliferation or number of (myo)fibroblasts between the experimental groups (see ESI Fig. S6 †).…”