Current knowledge and challenges associated with targeted delivery of neurotrophic factors into the central nervous system: focus on available approaches.

During the last decades, numerous basic and clinical studies have been conducted to assess the delivery efficiency of therapeutic agents into the brain and spinal cord parenchyma using several administration routes. Among conventional and in-progress administrative routes, the eligibility of stem cells, viral vectors, and biomaterial systems have been shown in the delivery of NTFs. Despite these manifold advances, the close association between the delivery system and regeneration outcome remains unclear. Herein, we aimed to discuss recent progress in the delivery of these factors and the pros and cons related to each modality.

Evaluation of the Effect of Hyaluronic Acid-Based Biomaterial Enriched With Tenascin-C on the Behavior of the Neural Stem Cells.

One of the most important natural extracellular constituents is hyaluronic acid (HA) with the potential to develop a highly organized microenvironment. In the present study, we enriched HA hydrogel with tenascin-C (TN-C) and examined the viability and survival of mouse neural stem cells (NSCs) using different biological assays. Following NSCs isolation and expansion, their phenotype was identified using flow cytometry analysis. Cell survival was measured using MTT assay and DAPI staining after exposure to various concentrations of 50, 100, 200, and 400 nM TN-C. Using acridine orange/ethidium bromide staining, we measured the number of live and necrotic cells after exposure to the combination of HA and TN-C. MTT assay revealed the highest NSCs viability rate in the group exposed to 100 nM TN-C compared to other groups, and a combination of 1% HA + 100 nM TN-C increased the viability of NSCs compared to the HA group after 24 hours. Electron scanning microscopy revealed the higher attachment of these cells to the HA + 100 nM TN-C substrate relative to the HA substrate. Epifluorescence imaging and DAPI staining of loaded cells on HA + 100 nM TN-C substrate significantly increased the number of NSCs per field over 72 hours compared to the HA group (P < 0.05). Live and dead assay revealed that the number of live NSCs significantly increased in the HA + 100 TN-C group compared to HA and control groups. The enrichment of HA substrate with TN-C promoted viability and survival of NSCs and could be applied in neural tissue engineering approaches and regenerative medicine.

Hyaluronic Acid and Regenerative Medicine: New Insights into the Stroke Therapy.

Stroke is known as one of the very important public health problems that are related to societal burden and tremendous economic losses. It has been shown that there are few therapeutic approaches for the treatment of this disease. In this regard, the present therapeutic platforms aim to obtain neuroprotection, reperfusion, and neuro recovery. Among these therapies, regenerative medicine-based therapies have appeared as new ways of stroke therapy. Hyaluronic acid (HA) is a new candidate, which could be applied as a regenerative medicine-based therapy in the treatment of stroke. HA is a glycosaminoglycan composed of disaccharide repeating elements (N-acetyl-Dglucosamine and D-glucuronic acid). Multiple lines of evidence demonstrated that HA has critical roles in normal tissues. It can be a key player in different physiological and pathophysiological conditions such as water homeostasis, multiple drug resistance, inflammatory processes, tumorigenesis, angiogenesis, and changed viscoelasticity of the extracellular matrix. HA has very important physicochemical properties i.e., availability of reactive functional groups and its solubility, which make it a biocompatible material for application in regenerative medicine. Given that HAbased bioscaffolds and biomaterials do not induce inflammation or allergies and are hydrophilic, they are used as soft tissue fillers and injectable dermal fillers. Several studies indicated that HA could be employed as a new therapeutic candidate in the treatment of stroke. These studies documented that HA and HA-based therapies exert their pharmacological effects via affecting stroke-related processes. Herein, we summarized the role of the extracellular matrix in stroke pathogenesis. Moreover, we highlighted the HA-based therapies for the treatment of stroke.