Semiautomated quantification of the fibrous tissue response to complex three-dimensional filamentous scaffolds using digital image analysis

Abstract

Fibrosis represents a relevant response to the implantation of biomaterials, which occurs not only at the tissue–material interface (fibrotic encapsulation) but also within the void fraction of complex three-dimensional (3D) biomaterial constructions (fibrotic ingrowth). Usual evaluation of the biocompatibility mostly depicts fibrosis at the interface of the biomaterial using semiquantitative scores. Here, the relations between encapsulation and infiltrating fibrotic growth are poorly represented. Virtual pathology and digital image analysis provide new strategies to assess fibrosis in a more differentiated way. In this study, we adopted a method previously used to quantify fibrosis in visceral organs to the quantification of fibrosis to 3D biomaterials. In a proof-of-concept study, we transferred the “Collagen Proportionate Area” (CPA) analysis from hepatology to the field of biomaterials. As one task of an experimental animal study, we used CPA analysis to quantify the fibrotic ingrowth into a filamentous scaffold after subcutaneous implantation. We were able to demonstrate that the application of the CPA analysis is well suited as an additional fibrosis evaluation strategy for new biomaterial constructions. The CPA method can contribute to a better understanding of the fibrotic interactions between 3D scaffolds and the host tissue responses.