Inflammation-mediated matrix remodeling of extracellular matrix-mimicking biomaterials in tissue engineering and regenerative medicine

Abstract

Extracellular matrix (ECM)-mimicking biomaterials are considered effective tissue-engineered scaffolds for regenerative medicine because of their biocompatibility, biodegradability, and bioactivity. ECM-mimicking biomaterials preserve natural microstructures and matrix-related bioactive components and undergo continuous matrix remodeling upon transplantation. The interaction between host immune cells and transplanted ECM-mimicking biomaterials has attracted considerable attention in recent years. Transplantation of biomaterials may initiate injuries and early pro-inflammation reactions characterized by infiltration of neutrophils and M1 macrophages. Pro-inflammation reactions may lead to degradation of the transplanted biomaterial and drive the matrix into a fetal-like state. ECM degradation leads to the release of matrix-related bioactive components that act as signals for cell migration, proliferation, and differentiation. In late stages, pro-inflammatory cells fade away, and anti-inflammatory cells emerge, which involves macrophage polarization to the M2 phenotype and leukocyte activation to T helper 2 (Th2) cells. These anti-inflammatory cells interact with each other to facilitate matrix deposition and tissue reconstruction. Deposited ECM molecules serve as vital components of the mature tissue and influence tissue homeostasis. However, dysregulation of matrix remodeling results in several pathological conditions, such as aggressive inflammation, difficult healing, and non-functional fibrosis. In this review, we summarize the characteristics of inflammatory responses in matrix remodeling after transplantation of ECM-mimicking biomaterials. Additionally, we discuss the intrinsic linkages between matrix remodeling and tissue regeneration. STATEMENT OF SIGNIFICANCE: Extracellular matrix (ECM)-mimicking biomaterials are effectively used as scaffolds in tissue engineering and regenerative medicine. However, dysregulation of matrix remodeling can cause various pathological conditions. Here, the review describes the characteristics of inflammatory responses in matrix remodeling after transplantation of ECM-mimicking biomaterials. Additionally, we discuss the intrinsic linkages between matrix remodeling and tissue regeneration. We believe that understanding host immune responses to matrix remodeling of transplanted biomaterials is important for directing effective tissue regeneration of ECM-mimicking biomaterials. Considering the close relationship between immune response and matrix remodeling results, we highlight the need for studies of the effects of clinical characteristics on matrix remodeling of transplanted biomaterials.

Keywords: Biomaterials; Extracellular matrix; Immune cell; Matrix remodeling; Tissue regeneration.