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. 2019 Oct 15;12:771–784. doi: 10.2147/CCID.S212599

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© 2019 Kim.

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Changes in immune cell appearance, shape, and size of CaHA particles, and collagen levels. (Upper) Immune cell appearance at corresponding stages of inflammation. Within the first few minutes of injury, platelets in the blood begin to stick to the injured site. Platelet-derived growth factors are released into the wound that causes the migration and division of cells during the proliferative phase of the inflammation phase. Within a few hours, polymorphonuclear neutrophils (PMN) arrive at the wound site and become the predominant cells in the wound for the first 2 days after the injury or injection, and phagocytosis debris and kill bacteria. Then, macrophages appear in the wound or injected area for phagocytosis bacteria and damaged tissue. Macrophage also functions in regeneration for wound healing and also stimulates to create granulation tissue and lay down a new extracellular matrix. When macrophages cannot clean the foreign body, macrophages fused together and became a foreign body giant cell (roughly 1 month after injection of CaHA filler). In fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix by excreting collagen and fibronectin. The re-epithelialization process does not occur after filler injection. (Middle) Changes in the shape and size of CaHA particles. Before injection, the size of CaHA particles was 36–52 microns. As time passes, the size was reduced, and particles were cleavaged. Larger-sized CaHA particles were surrounded only by FGCs and less than 10-micron CaHA particles by macrophages and FGCs both. (Bottom) Changes in collagen levels were associated with the amount of CaHA particle and immune cells. Initial collagen created with stimulation may be type III. As time passes, the amount of Collagen-III decreased and was replaced by Collagen-I in end stages of inflammation after CaHA biodegradation. This Collagen-I deposition may maintain somewhat the volume as CMC portion absorption. CMC was absorbed about 1 month after injection. CaHA particles were absorbed about 1 year after injection.