Fibroblasts: Diverse Cells Critical to Biomaterials Integration

Abstract

Fibroblasts are key participants in wound healing and inflammation, and are capable of driving the progression of tissue repair to fully functional tissue or pathologic scar, or fibrosis, depending on the specific mechanical and biochemical cues with which they are presented. Thus, understanding and modulating the fibroblastic response to implanted materials is paramount to achieving desirable outcomes, such as long-term implant function or tissue regeneration. However, fibroblasts are remarkably heterogeneous and can differ vastly in their contributions to regeneration and fibrosis. This heterogeneity exists between tissues and within tissues, down to the level of individual cells. This review will discuss the role of fibroblasts, the pitfalls of describing them as a collective, the specifics of their function, and potential future directions to better understand and organize their highly variable biology.

Keywords: biomaterials; fibroblast; fibrosis; inflammation; mechanobiology; mechanotransduction; review; wound healing.

Figure 1.

Timeline of wound healing and the foreign body response, broken into stages progressing from the initial response to the years beyond. Red, gross-scale tissue phenomena; green, cellular activity; gold, prominent cells.

Figure 2.

Range of cells which have been experimentally shown to become involved in fibrotic disease. Epithelial cells, tissue resident quiescent fibroblasts, microvasculature-associated pericytes, vascular endothelial cells, and circulating bone marrow derived fibrocytes can all differentiate into myofibroblasts and contribute toward fibrosis.

Figure 3.

Soluble cues driving fibroblast activation into a proliferative, secretory, and remodeling phenotype. EGF, epidermal growth factor; IFNγ, interferon-γ; IL(s), interleukin; PDGF, platelet-derived growth factor; SDF-1, stromal cell-derived factor 1; TGF-β, transforming growth factor β; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.