Emerging Implications for Extracellular Matrix-Based Technologies in Vascularized Composite Allotransplantation

Figure 4

Biomaterial-mediated tissue repair: The biomaterial-host interaction is a complex process composed of multiples stages. Following implantation, the surface of the material is covered with blood and plasma protein through a process known as the Vroman effect. In conjunction with hemostasis, the Vroman effect facilitates the formation of a temporary fibrin-rich matrix that mediates the interaction between native tissues and the implanted construct. This temporary matrix also facilitates cellular access into the material. The innate immune system is activated and a neutrophil accumulation at the periphery of the implant becomes histologically apparent within minutes to hours of implantation. In the following days, this neutrophil accumulation is gradually replaced by a macrophage infiltrate that facilitates scaffold degradation and matricryptic peptide release. The macrophage infiltrate then transitions from an M1 proinflammatory phenotype into an M2 proremodeling phenotype. Signaling molecules produced by the innate immune system and scaffold degradation products act synergistically to recruit stem/progenitor cells from nearby tissues and the bone marrow. Together this heterogeneous cell population known as the constructive cell infiltrate is responsible for further scaffold degradation, neomatrix deposition, and constructive functional tissue remodeling.