Aptamer Antagonists of Myelin-Derived Inhibitors Promote Axon Growth

Myelin of the adult central nervous system (CNS) is one of the major sources of inhibitors of axon regeneration following injury. The three known myelin-derived inhibitors (Nogo, MAG, and OMgp) bind with high affinity to the Nogo-66 receptor (NgR) on axons and limit neurite outgrowth. Here we show that RNA aptamers can be generated that bind with high affinity to NgR, compete with myelin-derived inhibitors for binding to NgR, and promote axon elongation of neurons in vitro even in the presence of these inhibitors. Aptamers may have key advantages over protein antagonists, including low immunogenicity and the possibility of ready modification during chemical synthesis for stability, signaling, or immobilization. This first demonstration that aptamers can directly influence neuronal function suggests that aptamers may prove useful for not only healing spinal cord and other neuronal damage, but may be more generally useful as neuromodulators

Hyaluronic acid and neural stem cells: implications for biomaterial design.

While in the past hyaluronic acid (HA) was considered a passive component with a primarily structural role in tissues, research over the past few decades has revealed its diverse and complex biological functions, resulting in a major ideological shift. HA is abundant during normal central nervous system (CNS) development and, although down-regulated, remains ubiquitous in adult extracellular matrix (ECM). Significant changes in HA content are associated with pathological conditions, including stroke, traumatic injury and multiple sclerosis, and these changes likely disrupt repair by endogenous neural stem cells (NSCs). In this review, we describe recent findings in HA biology relevant to NSCs-focusing on the potential of HA-NSC interactions to mediate CNS regeneration. Currently, HA biomaterials are being developed to counteract matrix changes associated with CNS injury and disease, thereby promoting NSC survival and directing differentiation. In parallel, HA-based biomaterials engineered to mimic the native CNS microenvironment are being used to investigate the relationship between NSCs and their HA-rich surroundings within a controlled experimental space. As our understanding of HA-NSC interactions improves, so will the therapeutic potential of HA-based biomaterials. Efforts to better understand the relationship between HA bioactivities and biomaterial design parameters are already underway. Although significant progress has been made improving techniques for controlled fabrication of HA-based hydrogels with precisely defined features, there is still much work to be done. Ideally, future designs will incorporate multiple types of microenvironmental cues - orthogonally tuned in time and space - to direct differentiation of NSCs into various specialized lineages within a single biomaterial platform

Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure.

Spinal cord injury (SCI) is a devastating condition that leaves patients with limited motor and sensory function at and below the injury site, with little to no hope of a meaningful recovery. Because of their ability to mimic multiple features of central nervous system (CNS) tissues, injectable hydrogels are being developed that can participate as therapeutic agents in reducing secondary injury and in the regeneration of spinal cord tissue. Injectable biomaterials can provide a supportive substrate for tissue regeneration, deliver therapeutic factors, and regulate local tissue physiology. Recent reports of increasing intraspinal pressure after SCI suggest that this physiological change can contribute to injury expansion, also known as secondary injury. Hydrogels contain high water content similar to native tissue, and many hydrogels absorb water and swell after formation. In the case of injectable hydrogels for the spinal cord, this process often occurs in or around the spinal cord tissue, and thus may affect intraspinal pressure. In the future, predictable swelling properties of hydrogels may be leveraged to control intraspinal pressure after injury. Here, we review the physiology of SCI, with special attention to the current clinical and experimental literature, underscoring the importance of controlling intraspinal pressure after SCI. We then discuss how hydrogel fabrication, injection, and swelling can impact intraspinal pressure in the context of developing injectable biomaterials for SCI treatment

Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure.

Spinal cord injury (SCI) is a devastating condition that leaves patients with limited motor and sensory function at and below the injury site, with little to no hope of a meaningful recovery. Because of their ability to mimic multiple features of central nervous system (CNS) tissues, injectable hydrogels are being developed that can participate as therapeutic agents in reducing secondary injury and in the regeneration of spinal cord tissue. Injectable biomaterials can provide a supportive substrate for tissue regeneration, deliver therapeutic factors, and regulate local tissue physiology. Recent reports of increasing intraspinal pressure after SCI suggest that this physiological change can contribute to injury expansion, also known as secondary injury. Hydrogels contain high water content similar to native tissue, and many hydrogels absorb water and swell after formation. In the case of injectable hydrogels for the spinal cord, this process often occurs in or around the spinal cord tissue, and thus may affect intraspinal pressure. In the future, predictable swelling properties of hydrogels may be leveraged to control intraspinal pressure after injury. Here, we review the physiology of SCI, with special attention to the current clinical and experimental literature, underscoring the importance of controlling intraspinal pressure after SCI. We then discuss how hydrogel fabrication, injection, and swelling can impact intraspinal pressure in the context of developing injectable biomaterials for SCI treatment

Deep learning for super-resolution vascular ultrasound imaging

Based on the intravascular infusion of gas microbubbles, which act as ultrasound contrast agents, ultrasound localization microscopy has enabled super resolution vascular imaging through precise detection of individual microbubbles across numerous imaging frames. However, analysis of high-density regions with significant overlaps among the microbubble point spread functions typically yields high localization errors, constraining the technique to low-concentration conditions. As such, long acquisition times are required for sufficient coverage of the vascular bed. Algorithms based on sparse recovery have been developed specifically to cope with the overlapping point-spread-functions of multiple microbubbles. While successful localization of densely-spaced emitters has been demonstrated, even highly optimized fast sparse recovery techniques involve a time-consuming iterative procedure. In this work, we used deep learning to improve upon standard ultrasound localization microscopy (Deep-ULM), and obtain super-resolution vascular images from high-density contrast-enhanced ultrasound data. Deep-ULM is suitable for real-time applications, resolving about 1250 high-resolution patches (128×128 pixels) per second using GPU acceleration