Erythropoietin in tissue engineering and beyond: a multifunctional macromolecule with emerging roles in organoids, immune modulation, and cancer research.

Erythropoietin (EPO), a glycoprotein hormone conventionally associated with erythropoiesis, has emerged as a versatile macromolecule with substantial therapeutic potential in tissue engineering and regenerative medicine. Beyond its role in red blood cell production, EPO displays pleiotropic effects, including angiogenesis, neuroprotection, anti-apoptosis, immunomodulation, and cell survival, making it a suitable agent for tissue repair and regeneration. This review explores EPO's biological characteristics and its integration into tissue-engineered constructs through innovative approaches such as scaffold immobilization, hydrogel encapsulation, and genetically modified cells for localized delivery. EPO has shown remarkable efficacy in regenerating diverse tissues, including bone, cartilage, neural, cardiac, dental, and skin, and in promoting wound healing. Additionally, its applications extend to advanced fields such as organoid development, immune modulation, and cancer research, further highlighting its versatility. Nevertheless, challenges such as maintaining EPO's bioactivity, achieving controlled and sustained delivery, and mitigating systemic or off-target effects remain significant barriers. Furthermore, its dual role in cancer biology necessitates a deeper understanding of its effects on tumor growth and immunity. Future advances in biomaterials and precision medicine could optimize EPO-based delivery systems to enable personalized therapeutic solutions. EPO stands poised to revolutionize tissue engineering, thus bridging laboratory innovation and clinical applications.