Sliding Fibers: Slidable, Injectable, and Gel-like Electrospun Nanofibers as Versatile Cell Carriers

Designing biomaterial systems that can mimic fibrous, natural extracellular matrix is crucial for enhancing the efficacy of various therapeutic tools. Herein, a smart technology of three-dimensional electrospun fibers that can be injected in a minimally invasive manner was developed. Open surgery is currently the only route of administration of conventional electrospun fibers into the body. Coordinating electrospun fibers with a lubricating hydrogel produced fibrous constructs referred to as <i>slid</i>able, <i>in</i>jectable, and <i>g</i>el-like (SLIDING) fibers. These SLIDING fibers could pass smoothly through a catheter and fill any cavity while maintaining their fibrous morphology. Their injectable features were derived from their distinctive rheological characteristics, which were presumably caused by the combinatorial effects of mobile electrospun fibers and lubricating hydrogels. The resulting injectable fibers fostered a highly favorable environment for human neural stem cell (hNSC) proliferation and neurosphere formation within the fibrous structures without compromising hNSC viability. SLIDING fibers demonstrated superior performance as cell carriers in animal stroke models subjected to the middle cerebral artery occlusion (MCAO) stroke model. In this model, SLIDING fiber application extended the survival rate of administered hNSCs by blocking microglial infiltration at the early, acute inflammatory stage. The development of SLIDING fibers will increase the clinical significance of fiber-based scaffolds in many biomedical fields and will broaden their applicability

Sliding Fibers: Slidable, Injectable, and Gel-like Electrospun Nanofibers as Versatile Cell Carriers

Designing biomaterial systems that can mimic fibrous, natural extracellular matrix is crucial for enhancing the efficacy of various therapeutic tools. Herein, a smart technology of three-dimensional electrospun fibers that can be injected in a minimally invasive manner was developed. Open surgery is currently the only route of administration of conventional electrospun fibers into the body. Coordinating electrospun fibers with a lubricating hydrogel produced fibrous constructs referred to as <i>slid</i>able, <i>in</i>jectable, and <i>g</i>el-like (SLIDING) fibers. These SLIDING fibers could pass smoothly through a catheter and fill any cavity while maintaining their fibrous morphology. Their injectable features were derived from their distinctive rheological characteristics, which were presumably caused by the combinatorial effects of mobile electrospun fibers and lubricating hydrogels. The resulting injectable fibers fostered a highly favorable environment for human neural stem cell (hNSC) proliferation and neurosphere formation within the fibrous structures without compromising hNSC viability. SLIDING fibers demonstrated superior performance as cell carriers in animal stroke models subjected to the middle cerebral artery occlusion (MCAO) stroke model. In this model, SLIDING fiber application extended the survival rate of administered hNSCs by blocking microglial infiltration at the early, acute inflammatory stage. The development of SLIDING fibers will increase the clinical significance of fiber-based scaffolds in many biomedical fields and will broaden their applicability

Highly Moldable Electrospun Clay-Like Fluffy Nanofibers for Three-Dimensional Scaffolds

The development of three-dimensional polymeric systems capable of mimicking the extracellular matrix is critical for advancing tissue engineering. To achieve these objectives, three-dimensional fibrous scaffolds with “clay”-like properties were successfully developed by coaxially electrospinning polystyrene (PS) and poly­(ε-caprolactone) (PCL) and selective leaching. As PS is known to be nonbiodegradable and vulnerable to mechanical stress, PS layers present at the outer surface were removed using a “selective leaching” process. The fibrous PCL scaffolds that remained after the leaching step exhibited highly advantageous characteristics as a tissue engineering scaffold, including moldability (i.e., clay-like), flexibility, and three-dimensional structure (i.e., cotton-like). More so, the “clay-like” PCL fibrous scaffolds could be shaped into any desired form, and the microenvironment within the clay scaffolds was highly favorable for cell expansion both in vitro and in vivo. These “electrospun-clay” scaffolds overcome the current limitations of conventional electrospun, sheet-like scaffolds, which are structurally inflexible. Therefore, this work extends the scope of electrospun fibrous scaffolds toward a variety of tissue engineering applications

Sticky “Delivering-From” Strategies Using Viral Vectors for Efficient Human Neural Stem Cell Infection by Bioinspired Catecholamines

Controlled release of biosuprastructures, such as viruses, from surfaces has been a challenging task in providing efficient ex vivo gene delivery. Conventional controlled viral release approaches have demonstrated low viral immobilization and burst release, inhibiting delivery efficiency. Here, a highly powerful substrate-mediated viral delivery system was designed by combining two key components that have demonstrated great potential in the fields of gene therapy and surface chemistry, respectively: adeno-associated viral (AAV) vectors and adhesive catecholamine surfaces. The introduction of a nanoscale thin coating of catecholamines, poly­(norepinephrine) (pNE) or poly­(dopamine) (pDA) to provide AAV adhesion followed by human neural stem cell (hNSC) culture on sticky solid surfaces exhibited unprecedented results: approximately 90% loading vs 25% (AAV_bare surface), no burst release, sustained release at constant rates, approximately 70% infection vs 20% (AAV_bare surface), and rapid internalization. Importantly, the sticky catecholamine-mediated AAV delivery system successfully induced a physiological response from hNSCs, cellular proliferation by a single-shot of AAV encoding fibroblast growth factor-2 (FGF-2), which is typically achieved by multiple treatments with expensive FGF-2 proteins. By combining the adhesive material-independent surface functionalization characters of pNE and pDA, this new sticky “delivering-from” gene delivery platform will make a significant contribution to numerous fields, including tissue engineering, gene therapy, and stem cell therapy