One-step fabrication of cell sheet-laden hydrogel for accelerated wound healing

Full-thickness skin wounds are have continued to be reconstructive challenges in dermal and skin appendage regeneration, and skin substitutes are promising tools for addressing these reconstructive procedures. Herein, the one-step fabrication of a cell sheet integrated with a biomimetic hydrogel as a tissue engineered skin for skin wound healing generated in one step is introduced. Briefly, cell sheets with rich extracellular matrix, high cell density, and good cell connections were integrated with biomimetic hydrogel to fabricate gel + human skin fibroblasts (HSFs) sheets and gel + human umbilical vein endothelial cells (HUVECs) sheets in one step for assembly as a cell sheet-laden hydrogel (CSH). The designed biomimetic hydrogel formed with UV crosslinking and ionic crosslinking exhibited unique properties due to the photo-generated aldehyde groups, which were suitable for integrating into the cell sheet, and ionic crosslinking reduced the adhesive force toward the substrate. These properties allowed the gel + cell sheet film to be easily released from the substrate. The cells in the harvested cell sheet maintained excellent viability, proliferation, and definite migration abilities inside the hydrogel. Moreover, the CSH was implanted into a full-thickness skin defects to construct a required dermal matrix and cell microenvironment. The wound closure rate reached 60.00 ± 6.26% on the 2nd day, accelerating mature granulation and dermis formation with skin appendages after 14 days. This project can provide distinct guidance and strategies for the complete repair and regeneration of full-thickness skin defects, and provides a material with great potential for tissue regeneration in clinical applications.

CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

Aberrant expression of circular RNAs(circ RNAs)is frequently linked to colorectal cancer(CRC).Here,we identified circ ZFR as a promising biomarker for CRC diagnosis and prognosis.Circ ZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence,advanced-stages,and metastasis.In both in vitro and in vivo settings,circ ZFR promoted the growth and spread while suppressing apoptosis of CRC.Exosomes with circ ZFR overexpression promoted the proliferation and migration of cocultured CRC cells.Mechanistically,epithelial splicing regulatory protein 1(ESRP1)in CRC cells may enhance the production of circ ZFR.BCL2-associated transcription factor 1(BCLAF1)bound to circ ZFR,which prevented its ubiquitinated degradation.Additionally,circ ZFR sponged mi R-3127-5p to boost rhotekin 2(RTKN2)expression.Our TCP1-CD-QDs nanocarrier was able to carry and deliver circ ZFR si RNA(si-circ ZFR)to the vasculature of CRC tissues and cells,which inhibited the growth of tumors in patient-derived xenograft(PDX)models.Taken together,our results show that circ ZFR is an oncogenic circ RNA,which promotes the development and spread of CRC in a BCLAF1 and mi R-3127-5p-dependent manner.Circ ZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.