Angiogenesis plays an important role in brain injury repair, which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area. As a major component of developing brain extracellular matrix, hyaluronic acid (HA) has attracted more attention as a supporting matrix for brain repair. In the present study, HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT (KLTWQELYQLKYKGI). The characterization of the hydrogel shows that it could provide a porous, three-dimensional scaffold structure, which has a large specific surface area available for cell adhesion and interaction. Compared with the unmodified HA hydrogel, the HA-KLT hydrogel could effectively promote the attachment, spreading and proliferation of endothelial cells in vitro. Furthermore, the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain. Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation. Moreover, they could efficiently inhibit the formation of glial scars at the injured sites. The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels, suggesting that HA-KLT hydrogel promoted angiogenesis in vivo. Collectively, the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.
Summary
Exploring the metabolic characteristics of indigenous PAH degraders is critical to understanding the PAH bioremediation mechanism in the natural environment. While stable‐isotopic probing (SIP) is a viable method to identify functional microorganisms in complex environments, the metabolic characteristics of uncultured degraders are still elusive. Here, we investigated the naphthalene (NAP) biodegradation of petroleum polluted soils by combining SIP, amplicon sequencing and metagenome binning. Based on the SIP and amplicon sequencing results, an uncultured Gammaproteobacterium sp. was identified as the key NAP degrader. Additionally, the assembled genome of this uncultured degrader was successfully obtained from the 13C‐DNA metagenomes by matching its 16S rRNA gene with the SIP identified OTU sequence. Meanwhile, a number of NAP degrading genes encoding naphthalene/PAH dioxygenases were identified in this genome, further confirming the direct involvement of this indigenous degrader in the NAP degradation. The degrader contained genes related to the metabolisms of several carbon sources, energy substances and vitamins, illuminating potential reasons for why microorganisms cannot be cultivated and finally realize their cultivation. Our findings provide novel information on the mechanisms of in situ PAH biodegradation and add to our current knowledge on the cultivation of non‐culturable microorganisms by combining both SIP and metagenome binning.
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