Mina Mekhail

Oligodendrocyte-protection and remyelination post-spinal cord injuries: A review

In the past four decades, the main focus of investigators in the field of spinal cord regeneration has been to devise therapeutic measures that enhance neural regeneration. More recently, emphasis has been placed on enhancing remyelination and providing oligodendrocyte-protection after a spinal cord injury (SCI). Demyelination post-SCI is part of the cascading secondary injury that takes place immediately after the primary insult; therefore, therapeutic measures are needed to reduce oligodendrocyte death and/or enhance remyelination during the acute stage, preserving neurological functions that would be lost otherwise. In this review a thorough investigation of the oligodendrocyte-protective and remyelinative molecular therapies available to date is provided. The advent of new biomaterials shown to promote remyelination post-SCI is discussed mainly in the context of a combinatorial approach where the biomaterial also provides drug delivery capabilities. The aim of these molecular and biomaterial-based therapies is twofold: (1) oligodendrocyte-protective therapy, which involves protecting already existing oligodendrocytes from undergoing apoptosis/necrosis; and (2) inductive remyelination, which involves harnessing the remyelinative capabilities of endogenous oligodendrocyte precursor cells (OPCs) at the lesion site by providing a suitable environment for their migration, survival, proliferation and differentiation. From the evidence reported in the literature, we conclude that the use of a combinatorial approach including biomaterials and molecular therapies would provide advantages such as: (1) sustained release of the therapeutic molecule, (2) local delivery at the lesion site, and (3) an environment at the site of injury that promotes OPC migration, differentiation and remyelination.

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.