VEGF-modified PLA/HA nanocomposite fibrous membrane for cranial defect repair in rats

Abstract

A major obstacle to bone tissue repair is the difficulty in establishing a rapid blood supply areas of bone defects. Vascular endothelial growth factor (VEGF)-infused tissue-engineered scaffolds offer a possible therapeutic option for these types of injuries. Their role is to accelerate angiogenesis and improve bone healing. In this study, we used electrostatic spinning and biofactor binding to construct polylactic acid (PLA)/hydroxyapatite (HA)-VEGF scaffold materials and clarify their pro-vascular role in bone defect areas for efficient bone defect repair. PLA/HA nanocomposite fibrous membranes were manufactured by selecting suitable electrostatic spinning parameters. Heparin and VEGF were bound sequentially, and then the VEGF binding and release curves of the fiber membranes were calculated. A rat cranial defect model was constructed, and PLA/HA fiber membranes bound with VEGF and unbound with VEGF were placed for treatment. Finally, we compared bone volume recovery and vascular recovery in different fibrous membrane sites. A VEGF concentration of 2.5 µg/mL achieved the maximum binding and uniform distribution of PLA/HA fibrous membranes. Extended-release experiments showed that VEGF release essentially peaked at 14 days. In vivo studies showed that PLA/HA fibrous membranes bound with VEGF significantly increased the number of vessels at the site of cranial defects, bone mineral density, bone mineral content, bone bulk density, trabecular separation, trabecular thickness, and the number of trabeculae at the site of defects in rats compared with PLA/HA fibrous membranes not bound with VEGF. VEGF-bound PLA/HA fibrous membranes demonstrate the slow release of VEGF. The VEGF binding process does not disrupt the morphology and structure of the fibrous membranes. The fibrous membranes could stimulate both osteogenesis and angiogenesis. Taken together, this research provides a new strategy for critical-sized bone defects repairing.