Biomimicking Fiber Scaffold as an Effective In Vitro and In Vivo MicroRNA Screening Platform for Directing Tissue Regeneration

Abstract

MicroRNAs effectively modulate protein expression and cellular response. Unfortunately, the lack of robust nonviral delivery platforms has limited the therapeutic application of microRNAs. Additionally, there is a shortage of drug‐screening platforms that are directly translatable from in vitro to in vivo. Here, a fiber substrate that provides nonviral delivery of microRNAs for in vitro and in vivo microRNA screening is introduced. As a proof of concept, difficult‐to‐transfect primary neurons are targeted and the efficacy of this system is evaluated in a rat spinal cord injury model. With this platform, enhanced gene‐silencing is achieved in neurons as compared to conventional bolus delivery ( p < 0.05). Thereafter, four well‐recognized microRNAs (miR‐21, miR‐222, miR‐132, and miR‐431) and their cocktails are screened systematically. Regardless of age and origin of the neurons, similar trends are observed. Next, this fiber substrate is translated into a 3D system for direct in vivo microRNA screening. Robust nerve ingrowth is observed as early as two weeks after scaffold implantation. Nerve regeneration in response to the microRNA cocktails is similar to in vitro experiments. Altogether, the potential of the fiber platform is demonstrated in providing effective microRNA screening and direct translation into in vivo applications.

Biomimicking Fiber Platform with Tunable Stiffness to Study Mechanotransduction Reveals Stiffness Enhances Oligodendrocyte Differentiation but Impedes Myelination through YAP‐Dependent Regulation

“…It is noteworthy that biochemical signaling greatly varies during development and in disease context. We demonstrated that electrospun fibers are suitable for incorporating drugs and genes [ 14,35,48 ] for screening purposes with good correlation between in vitro and in vivo regenerative outcomes. [ 48 ] Future studies could then include the synergistic combination of biochemicals (e.g., promyelinogenic factors like miR‐219/miR‐338 [ 49–52 ] with mechanical stiffness changes to verify the synergistic, antagonistic, or possible recovery effects.…”

RNA interference in glial cells for nerve injury treatment

“…Neurofilament protein-200 (NF-200) was significantly higher in miRNA-treated groups compared to control group (NT only) (b). Adapted with permission from N Zhang et al 54 …”

Electroresponsive Silk-Based Biohybrid Composites for Electrochemically Controlled Growth Factor Delivery

“…Current therapeutic procedures are surgical, employing biomaterials to bridge nerve defects with varying degrees of success [24][25][26]. To enhance the probability of successful outcomes, the use of pharmacological agents and biomolecules, such as microRNAs or growth factors to promote nerve regeneration have gained attention over the last few years [27][28][29]. Neurotrophins are one of many examples of these, which regulate extracellular signaling, neuronal survival and differentiation and axonal regeneration [30].…”