Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.

Improving Vascular Regeneration Performance of Electrospun Poly(ε‑Caprolactone) Vascular Grafts via Synergistic Functionalization with VE‑Cadherin/VEGF

In vivo,vascular endothelial growth factor(VEGF)and vascular endothelial cadherin(VE-cadherin)co-regulate the dynamic organization of endothelial cells during vascular sprouting,balancing angiogenesis and vascular stability.In this study,a novel bioactive surface integrating human VE-cadherin-Fc and VEGF-Fc fusion proteins was innovatively developed for the modification of poly(ε-caprolactone)(PCL)small-caliber electrospun fibrous grafts(VE-cad/VEGF-PCL)to promote the regeneration of functional endothelium and improve the patency of artificial vascular grafts.These fusion proteins self-assembled on the PCL fibers through the hydrophobic binding of Fc domains,improving surface hydrophilicity while reducing the adhesion of fibrinogen.In vitro results showed that the VE-cadherin/VEGF surface upregulated the expression of endogenous VE-cadherin and synergistically activated the VE-cadherin/VEGFR2/FAK/AKT/ERK signal transduction,which facilitated the functioning of human umbilical vein endothelial cells(HUVECs).Moreover,the VE-cadherin/VEGF surface significantly enhanced cellularization and capillary formation,then subsequently accelerated the regeneration of functional endothelium and smooth muscle in the VE-cad/VEGF-PCL grafts in a rat abdominal aorta replacement model.Together,these results highlight the advantages of VE-cadherin/VEGF surface in enhancing rapid endothelialization of electrospun vascular grafts and provide new insights into the design of cross-activating biomaterials.