Physical properties of scaffold materials promote tissue repair and regeneration by influencing the paracrine action of mesenchymal stem cells

Mesenchymal stem cells (MSCs) have gained considerable attention in tissue engineering due to their remarkable multilineage differentiation potential, recruitment of endogenous cells, and orchestration of a regenerative microenvironment via the secretion of trophic factors. Contemporary research increasingly underscores that, rather than direct differentiation into injured tissue cells, MSCs primarily facilitate tissue repair through the secretion of bioactive paracrine factors. Notably, the physical properties of scaffold materials have emerged as key regulators of MSC paracrine function. This review provides a comprehensive overview of how diverse physical characteristics of scaffold materials modulate the composition and concentration of MSC-derived paracrine factors, thereby shaping the cellular microenvironment to enhance tissue regeneration. By elucidating the mechanistic interplay between scaffold physicality and MSC paracrine function, we aim to inform the rational design of biomaterials for optimized regenerative therapies.