A reactive oxygen species-responsive hydrogel encapsulated with bone marrow derived stem cells promotes repair and regeneration of spinal cord injury

Spinal cord injury(SCI)is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes,such as excessive reactive oxygen species(ROS)produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment,leading to the widespread apoptosis of the neuron cells,glial and oligodendroctyes.In this study,a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells(BMSCs),which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment.The hydrogel could effectively encapsulate BMSCs,and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS,attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α),resulting in a reduced cell apoptosis in the spinal cord tissue.The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation,and improved the neurogenesis of the spinal cord tissue,and thus distinctly enhanced the motor functional recovery of SCI rats.Our work provides a combinational strategy against ROS-mediated oxidative stress,with potential applications not only in SCI,but also in other central nervous system diseases with similar pathological conditions.

Promotion of Neurite Outgrowth and Extension Using Injectable Welded Nanofibers

We report a general strategy to develop injectable welded nanofibers to facilitate the outgrowth and extension of neurites.In this case,nonwoven mats of uniaxially aligned poly(caprolactone)(PCL)nanofibers were firstly cut into several small pieces with fixed fiber lengths of 25,50 and 100µm,respectively,using a cryotome.A tissuelyser was employed to homogenize and disperse the short nanofibers to a homogeneous suspension.By tuning treatment duration from 100 s to 400 s,the temperature of the suspension was brought close to the melting point of PCL.As such,the short nanofibers were welded at their cross points while the fibers far away from the cross points remain the original structures.We showed that the viability of neuroblastoma SH-SY5Y cells and their neurite outgrowth and extension were enhanced with the use of such welded short nanofibers.Taken together,this study provides a simple way to generate injectable welded nanofibers,holding potential in affecting neurite outgrowth and extension for nerve repair,in particular,in the central nervous system.

Photothermal‑Triggered Structural Change of Nanofiber Scaffold Integrating with Graded Mineralization to Promote Tendon–Bone Healing

Scaffolds functionalized with graded changes in both fiber alignment and mineral content are more appealing for tendon-bone healing.This study reports the healing of rotator cuff injury using a heterogeneous nanofiber scaffold,which is associated with a structural gradating from aligned to random and an increasing gradient of mineral content in the same orientation.The photothermal-triggered structural change of a nanofiber scaffold followed by graded mineralization is key to constructing such scaffolds.This type of scaffold was found to be biocompatible and provide beneficial contact guidance in the manipulation of tendon-derived stem cell morphologies in vitro.Specifically,tenogenic and osteogenic differentiation of tendon-derived stem cells were simultaneously achieved using the fabricated scaffold.In vivo investigation also showed the improved healing of rabbit rotator cuff injuries based on immunohistochemical analysis and biomechanical investigation that indicates the promising potential of a dual-gradient nanofiber scaffold in clinical tendon-bone healing.

Role of neuroinflammation in ischemic stroke

Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke.