Hence, strategies still need to be optimized to simulate the dynamic and bilateral effects of the natural extracellular matrix (ECM) on the behavior of cells.
For example, excessive or persistent M2 activation may lead to redundant fibrosis. Nevertheless, the material's ability to regulate multiple events of the healing process and its effects on such events are often poorly considered. In these studies, various well-controlled functional scaffolds, which are capable of rapid or sustained delivery of the active ingredients, were generated. Modifications to the biomaterial include simple blend, chemical conjugation, and nanoencapsulation of growth factors (e.g., IL-4), prostaglandin E2, or plasmids. This concept has been applied on skin, skeletal muscle, heart, nerves, and other organ systems. A novel and widely accepted strategy in regenerative medicine concerns the development of optimized biological scaffolds endowing immunomodulatory properties that coordinate the M1-M2 polarization precisely and in a stage-dependent manner. M2 macrophages contribute to constructive bone remodeling by mediating the biomaterial-host interactions, leading to tissue integration and regeneration. Therefore, timely termination of the proinflammatory response by optimizing the M1-to-M2 transition at the early stages of bone injury is a prerequisite to successful bone healing. M2 macrophages secrete tissue repair signals, such as IL-10, TGF-β, BMP-2, and VEGF, which are able to recruit mesenchymal progenitor cells, promote angiogenesis, and induce cartilage and bone differentiation. A prolonged proinflammatory response may delay bone regeneration by hindering the M1-to-M2 phase transition of macrophages. At complex and severe bone injury sites, however, a large number of cytotoxic T cells and high levels of proinflammatory cytokines, such as IL-1, TNF, and IL-6, persist and induce alarming proinflammatory responses.
Subsequently, the anti-inflammatory M2 phenotype macrophages become dominant within the first 3 days. Simple fractures entirely heal on their own the inflammatory cytokines released during acute inflammation induce macrophage polarization into the M1 phenotype, which acquaints these cells with phagocytic and clearance properties. Interference with any of these processes may impede successful bone healing.
ECM TITANIUM 1.71 DOWNLOAD SERIES
Thus, PEM hydrogels may serve as promising biomaterials in bone tissue engineering.īone healing entails a well-orchestrated series of events, including early inflammatory immune regulation, angiogenesis, osteogenic differentiation, and biomineralization. These biological effects coordinated well with the natural process of bone regeneration. Eventually, PEM hydrogels promoted mature bone formation in large bone defects to a greater extent than collagen I hydrogels. These effects were also verified in a subcutaneous embedding model.
As bone repair progressed, PEM hydrogels promoted blood vessel migration, the development of relative larger blood vessels, and functional vascularization. During the early phase of repair, PEM hydrogels facilitated the M1-to-M2 transition of macrophages. The dynamic and multiphase effects of the hydrogels were evaluated using a rat critical-sized calvarial defect model in vivo. PEM hydrogels induced the recruitment and M2-polarization of macrophages, promoted the differentiation of MSCs into endothelial-like cells, HUVEC tube formation, osteogenic differentiation of primary calvarial osteoblasts and MSCs, and mineralization after being immersed in simulated body fluid. The effects of PEM hydrogels on the different phases of the healing process were assessed in vitro. PEM hydrogels were fully characterized compared with a collagen I hydrogel. Here, we fabricated an injectable periosteal extracellular matrix (PEM) hydrogel that dynamically integrates multiple biological functions and, therefore, acts at different stages of the fracture healing process. Bone healing is a complex physiological process initiated by early regulation of the inflammatory immunity and entails multiple events including angiogenesis, osteogenic differentiation, and biomineralization.