In vivo tracking of neuronal-like cells by magnetic resonance in rabbit models of spinal cord injury

In vitro experiments have demonstrated that neuronal-like cells derived from bone marrow mesen- chymal stem cells can survive, migrate, integrate and help to restore the function and behaviors of spinal cord injury models, and that they may serve as a suitable approach to treating spinal cord injury. However, it is very difficult to track transplanted cells in vivo. In this study, we injected su- perparamagnetic iron oxide-labeled neuronal-like cells into the subarachnoid space in a rabbit model of spinal cord injury. At 7 days after cell transplantation, a small number of dot-shaped low signal intensity shadows were observed in the spinal cord injury region, and at 14 days, the number of these shadows increased on T2-weighted imaging. Perl＇s Prussian blue staining detected dot-shaped low signal intensity shadows in the spinal cord injury region, indicative of superpara- magnetic iron oxide nanoparticle-labeled cells. These findings suggest that transplanted neu- ronal-like cells derived from bone marrow mesenchymal stem cells can migrate to the spinal cord injury region and can be tracked by magnetic resonance in vivo. Magnetic resonance imaging represents an efficient noninvasive technique for visually tracking transplanted cells in vivo.

Quantum dots-labeled polymeric scaffolds for in vivo tracking of degradation and tissue formation

The inevitable gap between in vitro and in vivo degradation rate of biomaterials has been a challenging factor in the optimal designing of scaffold’s degradation to be balanced with new tissue formation.To enable non-/minimum-invasive tracking of in vivo scaffold degradation,chemical modifications have been applied to label polymers with fluorescent dyes.However,the previous approaches may have limited expandability due to complicated synthesis processes.Here,we introduce a simple and efficient method to fluorescence labeling of polymeric scaffolds via blending with near-infrared(NIR)quantum dots(QDs),semiconductor nanocrystals with superior optical properties.QDs-labeled,3D-printed PCL scaffolds showed promising efficiency and reliability in quantitative measurement of degradation using a custom-built fiber-optic imaging modality.Furthermore,QDs-PCL scaffolds showed neither cytotoxicity nor secondary labeling of adjacent cells.QDs-PCL scaffolds also supported the engineering of fibrous,cartilaginous,and osteogenic tissues from mesenchymal stem/progenitor cells(MSCs).In addition,QDs-PCL enabled a distinction between newly forming tissue and the remaining mass of scaffolds through multi-channel imaging.Thus,our findings suggest a simple and efficient QDs-labeling of PCL scaffolds and minimally invasive imaging modality that shows significant potential to enable in vivo tracking of scaffold degradation as well as new tissue formation.

Pro-osteogenesis and in vivo tracking investigation of a dental implantation system comprising novel mTi implant and HYH-Fe particles

Insufficient early osteogenesis seriously affects the later stage osteogenic quality and osseointegration of dental implants.To promote early osteogenesis,we first designed a Ti dental implant with a built-in magnet(mTi)to produce a local static magnetic field(SMF).Then,a dental implantation system comprising the mTi implant and the superparamagnetic hydroxyapatite(HA:Yb/Ho-Fe,named HYH-Fe)particles was implanted into the alveolar bone of beagles.The results showed that the mTi+HYH-Fe group displayed better early osteogenesis and later stage osseointegration than the Ti+HA and mTi+HA groups.A combination of the local SMF(mTi)and superparamagnetic HYH-Fe particles had a positive effect on the pro-osteogenesis of Ti implants.The results also indicated that week 10 could be adopted as the key time point to evaluate the early osteogenic effect of the mTi+HYH-Fe implantation system,which would be a promising prospect for promotion of osteogenesis,in vivo tracking investigation of material-bone relationships,and clinical applications.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate

Extracellular matrix(ECM)undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored.Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo^(+)self-assembly composed of azobenzene derivatives(Azo^(+))stacked via cation-πinteractions and stabilized with RGD ligand-bearing poly(acrylic acid).Near-infrared-upconverted-ultraviolet light induces cis-Azo^(+)-mediated inflation that suppresses cation-πinteractions,thereby inflating liganded self-assembly.This inflation increases nanospacing of“closely nanospaced”ligands from 1.8 nm to 2.6 nm and the surface area of liganded selfassembly that facilitate stem cell adhesion,mechanosensing,and differentiation both in vitro and in vivo,including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo^(+)molecules and loaded molecules.Conversely,visible light induces trans-Azo^(+)formation that facilitates cation-πinteractions,thereby deflating self-assembly with“closely nanospaced”ligands that inhibits stem cell adhesion,mechanosensing,and differentiation.In stark contrast,when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly,the surface area of“distantly nanospaced”ligands increases,thereby suppressing stem cell adhesion,mechanosensing,and differentiation.Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified.This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.