RESUMO
Anal fistulae are abnormal hollow connections between the wall of the anal canal and the perianal skin around the anus that have remained a burden on the medical sector for centuries. The complexity of this disease is attributed to a number of factors such as the degree of associated sphincter muscle, concomitant illnesses, existence of multiple fistulous tracts and the number of previous interventions. Persistence of a complex anal fistula can cause a decline in patient's physical quality of life as well as impact on the psychological status of patients who often suffer from anxiety and depression. Surgical intervention remains the gold standard for treatment, however; the risk of incontinence and high recurrence potential has led to interest into developing alternative treatment approaches such as the use of biologics, bioactives and biomaterials. One potential reason for these varied outcomes could be the multifactorial interplay between genetic, immune-related, environmental, and microbial persistence factors on tissue regeneration. Recent observations have proposed that adverse inflammatory mediators may contribute more than microbial factors. The moderate to high success rates of biotechnological advances (mesenchymal stem cells and biomaterial scaffolds) show promise as therapies for the amelioration of adverse persistent factors while facilitating a means to closing the fistula tract. The purpose of this review is to outline recent advances in biologics and combination therapies to treat persistent factors associated with complex anal fistula.