Because
tissue responses to implants determine the success or failure
of tissue engineering products, fibroin/sericin-based scaffolds including
bionic silk scaffolds, native silk fibers, fibroin fibers, and regenerated
fibroin have been fabricated, and their biocompatibility was investigated.
Fibroin/sericin-based scaffolds were characterized by scanning electron
microscopy (SEM) and X-ray diffraction (XRD). Bionic silk scaffolds
were beneficial to silk fiber formation through self-assembly. Histological
and immunofluorescent staining analysis demonstrated that bionic silk
scaffolds did not show significant inflammatory responses. Immunization
analysis showed that soluble fibroin and sericin did not show obvious
immunogenicity. This work supplied an effective approach to design
fibroin/sericin-based scaffolds for tissue engineering and drug delivery.
Spinal cord injury (SCI) is an incurable trauma that frequently results in partial or complete loss of motor and sensory function. Massive neurons are damaged after the initial mechanical insult. Secondary injuries, which are triggered by immunological and inflammatory responses, also result in neuronal loss and axon retraction. This results in defects in the neural circuit and a deficiency in the processing of information. Although inflammatory responses are necessary for spinal cord recovery, conflicting evidence of their contributions to specific biological processes have made it difficult to define the specific role of inflammation in SCI. This review summarizes our understanding of the complex role of inflammation in neural circuit events following SCI, such as cell death, axon regeneration and neural remodeling. We also review the drugs that regulate immune responses and inflammation in the treatment of SCI and discuss the roles of these drugs in the modulation of neural circuits. Finally, we provide evidence about the critical role of inflammation in facilitating spinal cord neural circuit regeneration in zebrafish, an animal model with robust regenerative capacity, to provide insights into the regeneration of the mammalian central nervous system.
Increasing evidence shows that the physical properties of biomaterials play an important role in regulating cell behavior and function, especially the mechanical properties of biomaterials. Macrophages can also be multidirectionally regulated by mechanical factors in the microenvironment, which simultaneously mediate biomaterials response that triggered by foreign body reactions (FBR). However, how the stiffness of biomaterials regulates macrophages and the underlying mechanisms are still not well understood. Our study demonstrates that chitosan freeze-dried scaffolds with different elastic modulus can modulate the proliferative capacity, growth morphology and polarization behavior of macrophages. The compression tests and morphology observation confirmed that the prepared lyophilized chitosan scaffolds possessed varied stiffness. The fluorescence staining experiments showed that the RAW macrophage cell lines exhibited differences in proliferation and morphology on the freeze-dried scaffolds with different stiffness. Macrophages in the 5% group (elastic modulus of 106.7 kPa) had the largest number and mean cell area. Furthermore, ELISA and qPCR results illustrated that macrophage polarization towards the M1/M2 phenotype was strongly influenced by the stiffness of the lyophilized scaffolds. The study may provide new insights and references for designing the elastic moduli of biomaterials for regulating immune responsiveness.
Background
Anisotropic topologies are known to regulate cell-oriented growth and induce cell differentiation, which is conducive to accelerating nerve regeneration, while co-culture of endothelial cells (ECs) and Schwann cells (SCs) can significantly promote the axon growth of dorsal root ganglion (DRG). However, the synergistic regulation of EC and SC co-culture of DRG behavior on anisotropic topologies is still rarely reported. The study aims to investigate the effect of anisotropic topology co-cultured with Schwann cells and endothelial cells on dorsal root ganglion behavior for promoting peripheral nerve regeneration.
Methods
Chitosan/artemisia sphaerocephala (CS/AS) scaffolds with anisotropic topology were first prepared using micro-molding technology, and then the surface was modified with dopamine to facilitate cell adhesion and growth. The physical and chemical properties of the scaffolds were characterized through morphology, wettability, surface roughness and component variation. SCs and ECs were co-cultured with DRG cells on anisotropic topology scaffolds to evaluate the axon growth behavior.
Results
Dopamine-modified topological CS/AS scaffolds had good hydrophilicity and provided an appropriate environment for cell growth. Cellular immunofluorescence showed that in contrast to DRG growth alone, co-culture of SCs and ECs could not only promote the growth of DRG axons, but also offered a stronger guidance for orientation growth of neurons, which could effectively prevent axons from tangling and knotting, and thus may significantly inhibit neurofibroma formation. Moreover, the co-culture of SCs and ECs could promote the release of nerve growth factor and vascular endothelial growth factor, and up-regulate genes relevant to cell proliferation, myelination and skeletal development via the PI3K-Akt, MAPK and cytokine and receptor chemokine pathways.
Conclusions
The co-culture of SCs and ECs significantly improved the growth behavior of DRG on anisotropic topological scaffolds, which may provide an important basis for the development of nerve grafts in peripheral nerve regeneration.
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