Biomaterials for host cell recruitment and stem cell fate modulation for tissue regeneration: Focus on neuropeptide substance P

Substance P (SP) has been recently identified as an injury-inducible messenger responsible for promoting tissue regeneration in a variety of injury models, such as limb ischemia, myocardial infarction, and osteoarthritis. SP mobilizes host stem/progenitor cells, which are then recruited to the injury site. SP also modulates the inflammatory response and polarizes macrophages towards the M2 phenotype, which ultimately lead to accelerated tissue repair. SP has been delivered systemically or immobilized into scaffold materials but is easily cleaved by endogenous proteolytic enzymes; thus, its conjugation with a biomaterial may hold great promise for its use in regenerative medicine and tissue engineering applications. In addition, SP has been shown to induce stem/progenitor cell mobilization by binding to neurokinin-1 receptor. The aim of this review is to critically analyze the recent literature on the use of SP in regenerative medicine and tissue engineering and to explore further avenues. Moreover, we will seek to identify the challenges ahead and how these may be overcome.