Ischemic stroke was a leading cause of death and long‐term disability. It was an effective way to improve cerebral ischemia injury by promoting angiogenesis and neuroprotection. Vascular endothelial growth factor (VEGF) was a potent pro‐angiogenic factor, and had neuroprotective effect. A short peptide (PR1P) derived from the extracellular VEGF‐binding glycoprotein‐Prominin‐1 was reported to specifically bind to VEGF. In order to realize sustained release of VEGF, a bio‐functional peptide‐CBD‐PR1P was constructed, which target VEGF to collagen hydrogels to limit the diffusion of VEGF. When the collagen hydrogels loading with CBD‐PR1P and VEGF were injected into the cerebral ischemic cortex, increased angiogenesis, decreased apoptosis and enhanced neurons survival were observed in the ischemic area, that promoted the motor functional recovery of cerebral ischemic injury. Thus, this targeting delivery system of VEGF provided a promising therapeutic strategy for cerebral ischemia.
Spinal cord injury (SCI) will lead to irreversible damage of sensory and motor function of central nervous system, which seriously affects patient's quality of life. A variety of nerve engineering materials carrying various stem cells and cell growth factors had used to promote the repair of SCI, but they could not mimic the actual matric niche at spinal cord to promote cell proliferation and differentiation. Thus, developing novel biomaterial providing better niche of spinal cord is a new strategy to treat the severe SCI. In this study, we constructed porcine spinal cord decellularized matrix scaffold (SC-DM) with biocompatibility to load engineered basic fibroblast growth factoroverexpressing human umbilical cord mesenchymal stromal cells (bFGF-HUCMSCs) for treating SCI. The continuously released bioactive bFGF factors from grafted bFGF-HUCMSCs and three-dimensional niche by SC-DM promoted the differentiation of endogenous stem cells into neurons with nerve conduction function, leading a markedly motor function recovery of SCI. These results indicated that the functional bFGF-HUCMSCs/SC-DM scaffold provided more suitable matric niche for nerve cells, that would be a promising strategy for the clinical application of SCI.axon regeneration, basic fibroblast growth factor, human umbilical cord mesenchymal stromal cells, spinal cord decellularized matrix, spinal cord injury Grażyna Kami nska-WinciorWenli He and Chunying Shi contributed equally to this work.
Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor and plays an important role in therapy of myocardial infarction (MI). Currently, how to retain regional concentration and decrease rapid diffusion is critical for its clinical application of VEGF. In recent years, the application of targeting peptides has been developed rapidly and provides new strategies for the sustained release of VEGF. In present study, a bi‐functional EBP‐PR1P peptide was designed and bridged VEGF to injectable cardiac extracellular matrix (c‐ECM). Through EBP‐PR1P peptides, VEGF could specifically bind with c‐ECM to realize the sustained release, without impacting the bioactivity of VEGF. Then VEGF/EBP‐PR1P/c‐ECM scaffolds were constructed and administrated into rats with MI. The results showed VEGF/EBP‐PR1P/c‐ECM could promote angiogenesis, protect cardiomyocytes survival against apoptosis, and improve the recovery of cardiac function. In addition, the mechanism of EBP‐PR1P/VEGF was also investigated which canonical downstream of VEGF‐Akt signaling pathway was activated. These results showed specific VEGF/EBP‐PR1P/c‐ECM scaffolds served as promising delivery system for VEGF that facilitated the functional recovery of MI.
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