Injectable chitosan-based scaffolds in regenerative medicine and their clinical translatability

Injectable scaffolds (IS) are polymeric solutions that are injected in vivo and undergo gelation in response to physiological or non-physiological stimuli. Interest in using IS in regenerative medicine has been increasing this past decade. IS are administered in vivo using minimally invasive surgery, which reduces hospitalization time and risk of surgical wound infection. Here, chitosan is explored as an excellent candidate for developing IS. A literature search reveals that 27% of IS publications in the past decade investigated injectable chitosan scaffolds (ICS). This increasing interest in chitosan stems from its many desirable physicochemical properties. The first section of this Progress Report is a comprehensive study of all physical, chemical, and biological stimuli that have been explored to induce ICS gelation in vivo. Second, the use of ICS is investigated in four major regenerative medicine applications, namely bone, cartilage, cardiovascular, and neural regeneration. Finally, an overall critique of the ICS literature in light of clinical translatability is presented. Even though ICS have been widely explored in the literature, very few have progressed to clinical trials. The authors discuss the current barriers to moving ICS into the clinic and provide suggestions regarding what is needed to overcome those challenges.