Construction of Dual-Biofunctionalized Chitosan/Collagen Scaffolds for Simultaneous Neovascularization and Nerve Regeneration

Abstract

Biofunctionalization of artificial nerve implants by incorporation of specific bioactive factors has greatly enhanced the success of grafting procedures for peripheral nerve regeneration. However, most studies on novel biofunctionalized implants have emphasized the promotion of neuronal and axonal repair over vascularization, a process critical for long-term functional restoration. We constructed a dual-biofunctionalized chitosan/collagen composite scaffold with Ile-Lys-Val-Ala-Val (IKVAV) and vascular endothelial growth factor (VEGF) by combining solution blending, in situ lyophilization, and surface biomodification. Immobilization of VEGF and IKVAV on the scaffolds was confirmed both qualitatively by staining and quantitatively by ELISA. Various single- and dual-biofunctionalized scaffolds were compared for the promotion of endothelial cell (EC) and Schwann cell (SC) proliferation as well as the induction of angiogenic and neuroregeneration-associated genes by these cells in culture. The efficacy of these scaffolds for vascularization was evaluated by implantation in chicken embryos, while functional repair capacity in vivo was assessed in rats subjected to a 10 mm sciatic nerve injury. Dual-biofunctionalized scaffolds supported robust EC and SC proliferation and upregulated the expression levels of multiple genes and proteins related to neuroregeneration and vascularization. Dual-biofunctionalized scaffolds demonstrated superior vascularization induction in embryos and greater promotion of vascularization, myelination, and functional recovery in rats. These findings support the clinical potential of VEGF/IKVAV dual-biofunctionalized chitosan/collagen composite scaffolds for facilitating peripheral nerve regeneration, making it an attractive candidate for repairing critical nerve defect. The study may provide a critical experimental and theoretical basis for the development and design of new artificial nerve implants with excellent biological performance.

Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury

“…The NF materials embellished with VEGF-A makes this possible, which also exhibit beneficial effects and clinical translational prospects for treating diseases, such as creating excellent microenvironmental stimuli for ischemia-associated neuronal regeneration and vascular remodeling in traumatic brain injury or indirect extracranial-intracranial (EC-IC) vascular bypass procedures (ie, encephalomyosynangiosis). 16,17,45,46 Mitochondria are critical cellular organelles that maintain energy and metabolism, stress response, and neuronal activities in the brain. Mitochondrial dysfunction is a contributing factor to the pathology of multiple human conditions including OGD.…”

In Situ 3D Bioprinting Living Photosynthetic Scaffolds for Autotrophic Wound Healing

“…Unfortunately, it is often difficult to fabricate the scaffolds with custom sizes and dimensions, which could adequately cover the wounds with varying depth or topography [ 18 ]. In addition, the insufficient nutrient and oxygen availability, particularly in the central regions of the macroscale scaffolds, compromises the overall therapeutic efficacy and results in poor regenerative outcomes [ 19 – 21 ]. Although many oxygen-delivery stratagems through incorporating inorganic peroxides, liquid peroxides, or fluorocarbons into the scaffolds have been made to alleviate systemic hypoxia, promote angiogenesis, enhance collagen remodeling, and accelerate wound closure, these oxygen-generating systems typically provide oxygen for several days and cannot sustain sufficient oxygen over the entire healing process [ 22 , 23 ].…”

Bioactivated Oxidized Polyvinyl Alcohol towards Next-Generation Nerve Conduits Development

“…Comparing the two functionalization strategies, mechanical incorporation of the peptide probably allows for a more effective entrapment of the motif within the hydrogel mesh, not strictly depending on C=O sites (oxidation degree: 1% [ 5 ]) for IKVAV. Decoration of 2-dimensional or 3-dimensional supports by IKVAV is broadly recognized as a promising method to enhance cell adhesion, induce neural differentiation and promote nerve regeneration [ 32 , 33 , 34 ]; however, peptide bioactivity is affected by surface peptide density [ 35 ] that here might be too low, as it strictly depends on polymer carbonyl groups content (in our case, 1%). This hypothesis could therefore justify the unpromising results displayed by the OxPVA-IKVAV scaffolds.…”