Bone remodeling-inspired dual delivery electrospun nanofibers for promoting bone regeneration

Developing a highly bioactive bone tissue engineering scaffold that can modulate the bone remodeling process for promoting bone regeneration is a great challenge. In order to tackle this issue, inspired by the balance between bone resorption and formation in the bone remodeling process, here we developed a mesoporous silicate nanoparticle (MSN)-based electrospun polycaprolactone (PCL)/gelatin nanofibrous scaffold to achieve dual delivery of alendronate (ALN) and silicate for a synergetic effect in modulating bone remodeling, where ALN inhibited the bone-resorbing process via preventing guanosine triphosphate-related protein expression, and silicate promoted the bone-forming process via improving vascularization and bone calcification. The scaffold was successfully prepared by encapsulation of ALN into MSNs (ALN@MSNs) and co-electrospinning of an acetic acid-mediated PCL/gelatin homogeneous solution with well-dispersed ALN@MSNs. The results of ALN and Si element release profiles indicated that the ALN@MSN-loaded nanofibers achieved dual release of ALN and silicate (produced due to the hydrolysis of MSNs) simultaneously. The bone repair data from a rat critical-sized cranial defect model revealed that the developed strategy accelerated the healing time from 12 weeks to 4 weeks, almost three times faster, while the other nanofiber groups only had limited bone regeneration at 4 weeks. In addition, we used interactive double-factor analysis of variance for the data of bone volume and maturity to evaluate the synergetic effect of ALN and silicate in promoting bone regeneration, and the result clearly proved our original design and hypothesis. In summary, the presented bone remodeling-inspired electrospun nanofibers with dual delivery of ALN and silicate may be highly promising for bone repair in the clinic.