Hydrogel-based chondrocyte implantation presents a promising tissue engineering strategy for cartilage repair. However, the widely used elastic hydrogels usually restrict cell volume expansion and induce the dedifferentiation of encapsulated chondrocytes. To address this limitation, a photoannealed granular hydrogel (GH) composed of hyaluronic acid, polyethylene glycol, and gelatin was formulated for cartilage regeneration in this study. The unannealed GH prepared by Diels–Alder cross-linked microgels could be mixed with chondrocytes and delivered to cartilage defects by injection, after which light was introduced to anneal the scaffold, leading to the formation of a stable and microporous chondrocyte deploying scaffold. The in vitro studies showed that GH could promote the volume expansion and morphology recovery of chondrocytes and significantly improve their chondrogenic phenotype compared to the nongranular hydrogel (nGH) with similar compositions. Further in vivo studies of subcutaneous culture and the rat full-thickness cartilage defect model proved that chondrocyte loaded GH could significantly stimulate hyaline cartilage matrix deposition and connection, therefore facilitating hyaline-like cartilage regeneration. Finally, the mechanistic study revealed that GH might improve chondrogenic phenotype via activating the AMP-activated protein kinase/glycolysis axis. This study proves the great feasibility of GHs as in situ chondrocyte deploying scaffolds for cartilage regeneration and brings new insights in designing hydrogel scaffold for cartilage tissue engineering.
The right parietal lobe plays an important role in body image, and disorders of body image emerge after lesions in the parietal lobe or with parietal lobe epilepsy. Body image disorder also often accompanies upper-limb amputation, in which the patient misperceives that their missing limb is still part of their body. Cortical reorganization is known to occur after upper-limb amputation, but it is not clear how widespread and to what degree functional connectivity (FC) is reorganized post-amputation, nor whether such changes might be related to misperceptions of body image. Twenty-four subjects who had a traumatically upper-limb amputees (ULAs) and 24 age-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. Regions of interest (ROIs) in the right superior parietal gyrus (SPG_R) and right inferior parietal lobule (IPL_R) were defined using BrainNet Viewer. We calculated the amplitude of low-frequency fluctuations (ALFF) in ROIs and correlated the ROI mean amplitude of low-frequency fluctuations (mALFF) and mean scores on the phantom limb sensation (PLS) scale and beck depression index (BDI). We also calculated ROIs and whole-brain FC. Compared to the HC group, we observed significantly increased activation (mALFF) in ROIs of the ULA group. Moreover, correlation analyses revealed a significant positive correlation between ROI mALFF and scores on the PLS. There was a significant negative correlation between the SPG_R mALFF and BDI scores. Seed-based, whole-brain FC analysis revealed that FC in the ULA group significantly decreased in many brain regions across the entire brain. The right parietal lobe appears to be involved in some aspect of body awareness and depression in amputation patients. Upper-limb amputation results not only in reorganization in the local brain area formerly representing the missing limb, but also results in more widespread reorganization through FC changes in whole brain.
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