Potential of Chitosan and Its Derivatives for Biomedical Applications in the Central Nervous System

Abstract

It is well known that the central nervous system (CNS) has a limited regenerative capacity and that many therapeutic molecules cannot cross the blood brain barrier (BBB). The use of biomaterials has emerged as an alternative to overcome these limitations. For many years, biomedical applications of chitosan have been studied due to its remarkable biological properties, biocompatibility, and high versatility. Moreover, the interest in this biomaterial for CNS biomedical implementation has increased because of its ability to cross the BBB, mucoadhesiveness, and hydrogel formation capacity. Several chitosanbased biomaterials have been applied with promising results as drug, cell and gene delivery vehicles. Moreover, their capacity to form porous scaffolds and to bear cells and biomolecules has offered a way to achieve neural regeneration. Therefore, this review aims to bring together recent works that highlight the potential of chitosan and its derivatives as adequate biomaterials for applications directed toward the CNS. First, an overview of chitosan and its derivatives is provided with an emphasis on the properties that favor different applications. Second, a compilation of works that employ chitosan-based biomaterials for drug delivery, gene therapy, tissue engineering, and regenerative medicine in the CNS is presented. Finally, the most interesting trends and future perspectives of chitosan and its derivatives applications in the CNS are shown.

Chitosan-Hydrogel Polymeric Scaffold Acts as an Independent Primary Inducer of Osteogenic Differentiation in Human Mesenchymal Stromal Cells

“…Scaffolds are three-dimensional porous structures playing a pivotal role in regenerative medicine and tissue engineering for the repair of tissue and organs [36,37]. Different materials, both synthetized and printed, are suitable for cell culture and sustaining the development of native tissue [38][39][40].…”

Particles Containing Cells as a Strategy to Promote Remyelination in Patients With Multiple Sclerosis

“…While many routes of administration are available (80), nasal administration allows passage to the brain (81), and has been used for such drugs as anti-LINGO-1 (82), teriflunomide (83), and carbamazepine (84). Nasal administration of chitosan hydrogel has been used as a treatment for Alzheimer disease or biomedical applications in the CNS (85,86). While there is less evidence on the transportation of cells than there is for drugs, chitosan is known to permit differentiation of both NSCs (87) and OPCs (88).…”

“…and BBB penetration enhancement properties that make it a great substrate for nose-to-brain approaches (76,86,97). For tissue engineering and regenerative medicine, chitosan and its derivatives have shown to promote axonal regeneration, antiinflammation, and to successful deliver neurotrophic factors and cells with a consequently functional recovery (108).…”

“…Several syntethic polymers or natural biomaterials have been used for CNS applications, chitosan is nowadays one of the leading substrates, employed as it can be found in nature or as a modified derivative. In biomolecules delivery, it stands out for its mucoadhesive and BBB penetration enhancement properties that make it a great substrate for nose-to-brain approaches ( 76 , 86 , 97 ). For tissue engineering and regenerative medicine, chitosan and its derivatives have shown to promote axonal regeneration, anti-inflammation, and to successful deliver neurotrophic factors and cells with a consequently functional recovery ( 108 ).…”

“…For tissue engineering and regenerative medicine, chitosan and its derivatives have shown to promote axonal regeneration, anti-inflammation, and to successful deliver neurotrophic factors and cells with a consequently functional recovery ( 108 ). In this way, chitosan-based biomaterials have become increasingly popular to use, alone or in combination with other molecules ( 86 ).…”