Small intestinal submucosa: superiority, limitations and solutions, and its potential to address bottlenecks in tissue repair.

Over the past few decades, small intestinal submucosa (SIS), a naturally occurring decellularized extracellular matrix (ECM), has attracted much attention in tissue repair because it can provide plentiful bioactive factors and a biomimetic three-dimensional microenvironment to induce desired cellular functions. In this article, the state-of-the-art research studies on SIS are reviewed, which are mainly centered on three aspects: (1) main superiority such as remarkable bioactivity, low immunogenicity, satisfactory resorbability and promising recellularization; (2) current efforts to overcome its limitations mainly focusing on reducing the naturally occurring heterogeneity, controlling the degradation rate and improving the mechanical properties; (3) great potential in solving the bottleneck problems encountered in repairing various tissues with particular emphasis on cardiovascular, urogenital, abdominal wall, skin, musculotendinous, gastrointestinal, vaginal, and bone tissues. In addition, future research trends are proposed in the conclusion and perspectives section.