Harnessing blood clot as a native scaffold for orchestrating tissue repairs and regeneration

Abstract As a natural endogenous bioreactor, the dynamic microenvironment of blood clots holds significant and underappreciated potential for tissue regeneration. This review systematically delineates the clot's core pathophysiology, including its fibrin network, diverse bioactive molecules, and cellular components, along with the key regulatory factors that shape its microenvironment. This paper further clarifies the differential regulatory mechanisms of blood clots in tissue regeneration, which vary across different tissue repair processes and are influenced by various pathological conditions such as inflammation. In clinical translation, autologous blood clots and their derivatives have shown promising results in skin healing, regenerative endodontics, and bone repair. Yet, challenges like insufficient mechanical strength and variable individual efficacy persist. Concurrently, the development of biomimetic materials that mimic fibrin's topology and integrate sequential growth factor release demonstrates enhanced hemostatic and osteogenic capabilities. By analyzing these advances, this review positions the blood clot as a novel paradigm to guide future biomaterial design, offering innovative solutions for complex tissue engineering and repairs.