The non-scaffold effects of natural polysaccharides in promoting organ regeneration: a review

Natural polysaccharides are known for their scaffold-based roles in tissue engineering, but their non-scaffold bioactivities in promoting organ regeneration remain poorly understood.This review aims to systematically summarizes the latest research advances in natural polysaccharides promoting organ regeneration through non-scaffold mechanisms, exploring their multifaceted actions, including creating a pro-regenerative microenvironment (e.g., immune regulation, extracellular matrix (ECM) remodeling, and gut microbiota-mediated short-chain fatty acids (SCFAs)), regulating stem cell proliferation and differentiation, promoting angiogenesis, and other effects like epigenetic regulation, antioxidant activity, and mitochondrial function modulation. Also outline their broad application potential in the regeneration and repair of multiple organ systems, including skin, heart, nerves, liver, and intestine. Furthermore, we discuss current challenges and future development directions, aiming to effectively exploit the therapeutic potential of natural polysaccharides in regenerative medicine and provide novel strategies for addressing organ repair challenges.