Specific bio‐functionalCBD‐PR1Ppeptide bindingVEGFto collagen hydrogels promotes the recovery of cerebral ischemia in rats

Abstract

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.

Proliferative and Osteogenic Supportive Effect of VEGF-Loaded Collagen-Chitosan Hydrogel System in Bone Marrow Derived Mesenchymal Stem Cells

“…The drug-releasing pattern of VEGF from a collagen HG and its angiogenesis behavior was previously investigated by Tabata et al [34]. In addition, VEGF was loaded with a collagen HG for neural stem cell regeneration [28], cerebral ischemia in rats [26], pancreatic islet vascularization [35], angiogenesis [36], and bone regeneration [37,38]. In parallel, VEGF was previously incorporated with a chitosan HG for odontogenic dental pulp stem cell differentiation [39,40], therapeutic neovascularization [41], wound healing [42], acute myocardial infarction [43], blood vessel regeneration [44], and bone regeneration [45].…”

“…Additionally, VEGF plays a crucial role in maintaining normal physiological processes and several pathologies such as retinopathies and cancer [23][24][25]. Previously, a VEGF-loaded collagen HG promoted the recovery of cerebral ischemia in rats [26], myogenesis and innervation after subcutaneous implantation in nude mice [27], and neural tissue regeneration [28]. Different types of HGs were fabricated with VEGF containing PEGylated fibrinogen and hyaluronic acid for myocardial infarction [29,30], hyaluronic acid for bioprosthetic heart valves [31], decellularized adipose tissue for angiogenesis [32], and fibrinogen-alginate for plasticity in an injured spinal cord [33].…”

Functional recovery of myocardial infarction by specific EBP‐PR1P peptides bridging injectable cardiac extracellular matrix and vascular endothelial growth factor

“…In addition, although VEGF was a key component for angiogenesis, it was also reported the blood vessels induced by VEGF were immature and permeable 47,48 . Beside gathering VEGF in biomaterial scaffolds, the coordination of additional factors with VEGF was another alternative strategy and angiopoietin‐1 (Ang‐1) was a promising synergetic factor of VEGF 49 . Studies demonstrated that VEGF and Ang‐1 collaborated to regulate vascular formation and decrease VEGF‐induced vascular permeability.…”

“…47,48 Beside gathering VEGF in biomaterial scaffolds, the coordination of additional factors with VEGF was another alternative strategy and angiopoietin-1 (Ang-1) was a promising synergetic factor of VEGF. 49 Studies demonstrated that VEGF and Ang-1 collaborated to regulate vascular formation and decrease VEGF-induced vascular permeability. During this process, VEGF acts early in vascular development by contributing to initiate proliferation and migration of endothelial cells and can promote the formation of new vessel in early stage; whereas Ang-1 is required to recruit vascular smooth muscle cells and to stabilize of new-formed vessels to form mature vessels.…”

Perspective insights into hydrogels and nanomaterials for ischemic stroke

“…Both VEGF and bFGF are well-known as the most potent proangiogenic factors, and their high expression stimulates the development and maturation of blood vessels ( Cecerska-Heryc et al, 2022 ). Various biomaterials have been used for the angiogenesis and neurological recovery after IS by directly delivering proangiogenic factors or indirectly regulating related upstream pathways and microenvironment ( Somaa et al, 2017 ; Zenych et al, 2021 ; Yanev et al, 2022 ; Yin et al, 2022 ). For example, a histidine-tagged VEGF-laminin-rich sponge is confirmed as a powerful scaffold to enhance the angiogenic activity in vivo experiments of mice stroke models ( Oshikawa et al, 2017 ).…”