Regeneration and repair processes are critical in healing damages caused by injury, disease, and aging. In regeneration, the damaged tissue is entirely replaced with new growth that restores the original architecture and function. In contrast, tissue repair usually results in a fixed tissue architecture involving scar formation. Scars generally do not reestablish tissue function and may also exhibit structural abnormalities at the injury site.
All animals have varying degrees of regenerative capabilities, but only some animals exhibit exceptional regeneration, such as generating an entire organ. For example, salamanders have a specialized population of stem cells that plays a significant role in regenerating fully functional limbs and tails. In mammals, only a few adult tissues like the liver, epithelium of the gut, and bone marrow can regenerate after an injury. The planarian flatworms, with a much simpler body structure, are capable of whole-body regeneration; if a planarium is cut into several pieces, each piece can develop into a completely new organism. Similarly, the hydra can regenerate its whole body even from a small fragment.
The regeneration process begins with the crucial step of covering the injury site. The epidermal cells migrate to the injury site, forming a thick covering called the apical epidermal cap. This is followed by clustering of undifferentiated fibroblast cells underneath the cap, forming a blastema. The blastema is a population of stem cells that has the potential to differentiate into any tissue or organ. The blastema is supplied with oxygen and nutrients via a new blood capillary network, allowing the cells to divide and differentiate.
The repair mechanism involves four phases: hemostasis, inflammation, proliferation, and remodeling. After an injury, the exposure of collagen— a structural protein in the walls of blood vessels— begins a coagulation cascade and vasoconstriction, thus, minimizing blood loss. During hemostasis, the clot fills the wound bed, providing a temporary matrix for the movement of various cells such as macrophages, neutrophils, and platelets. Platelet degranulation activates the complement cascade that stimulates inflammatory cells to attack the bacteria. During the proliferation phase, various cytokines and growth factors are released into the wound site, signaling the cells to proliferate and heal the wound. The final repair phase involves forming scar tissue that marks the completion of repair.
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