Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for Cranial Bone Regeneration

Abstract

An ideal synthetic bone graft is a combination of the porous and nanofibrous structure presented by natural bone tissue as well as osteoinductive biochemical factors such as bone morphogenetic protein 2 (BMP-2). In this work, ultralight 3D hybrid nanofiber aerogels composed of electrospun PLGA-collagen-gelatin and Sr-Cu codoped bioactive glass fibers with incorporation of heptaglutamate E7 domain specific BMP-2 peptides have been developed and evaluated for their potential in cranial bone defect healing. The nanofiber aerogels are surgically implanted into 8 mm × 1 mm (diameter × thickness) critical-sized defects created in rat calvariae. A sustained release of E7-BMP-2 peptide from the degradable hybrid aerogels significantly enhances bone healing and defect closure over 8 weeks in comparison to unfilled defects. Histomorphometry and X-ray microcomputed tomography (µ-CT) analysis reveal greater bone volume and bone formation area in case of the E7-BMP-2 peptide loaded hybrid nanofiber aerogels. Further, histopathology data divulged a near complete nanofiber aerogel degradation along with enhanced vascularization of the regenerated tissue. Together, this study for the first time demonstrates the fabrication of 3D hybrid nanofiber aerogels from 2D electrospun fibers and their loading with therapeutic osteoinductive BMP-2 mimicking peptide for cranial bone tissue regeneration.

Optimized Bioactive Glass: the Quest for the Bony Graft

“…More specifically, the sol–gel route allows the simplification of BAG to ternary (SiO 2 ‐CaO‐P 2 O 5 ) and binary (SiO 2 ‐CaO) systems containing up to 90 wt% SiO 2 (instead of 60 wt% for melt‐derived BAG) . Another key advantage of the sol–gel process is the diversity of shapes it offers: BAG can be fabricated under the form of nanoparticles, fibers, coating, particulates, monoliths or scaffolds …”

Electrospun Fibrous Architectures for Drug Delivery, Tissue Engineering and Cancer Therapy

“…When implanted in rat calvarium defects for 6 weeks, FGF2/FGF18 loading substantially increased the hard tissue ingrowth regions, which was evidenced by the highly increased bone volume and bone surface density from micro‐CT images. In the study of Weng et al, ultralight 3D fibrous aerogels composed of electrospun PLGA/collagen/gelatin fibers and Sr–Cu co‐doped bioactive glass fibers were constructed by combining electrospinning and freeze‐drying methods for cranial bone defect healing ( Figure a). Heptaglutamate E7 domain specific BMP‐2 peptides were further conjugated onto the optimized scaffolds for osteoinductive feature.…”

“…c3/c6) Peptide‐loaded aerogels group (4w/8w). Reproduced with permission . Copyright 2018, John Wiley and Sons.…”

Three‐dimensional electrospun nanofibrous scaffolds for bone tissue engineering

“…Similar to grinding in liquid nitrogen, sonication (Lee et al, ; Weng et al, ), smashing (Duan et al, ) and aminolysis (Ahmad et al, ) were also applied to broken small pieces of nanofibers, and the subsequent process was similar to the dispersion‐shaping technique. Since then, a series of similar studies have successfully fabricated nanofibrous aerogels of different materials by the dispersion‐shaping technique and explored their potential for application in bone tissue engineering.…”

“…In addition, due to the good physical adsorption capacity of hydroxyapatite for peptide drugs, E7‐BMP‐2 peptide (a BMP‐2 derived peptide) could be loaded on the hydroxyapatite‐rich nanofibers after biomineralization, thereby achieving a sustained release and preserving the biological activity of the loaded peptides. In vivo experiments have shown that E7‐BMP‐2 peptide loaded three‐dimensional (3D) nanofibrous scaffolds can better promote the bone regeneration in defect area than unmodified ones (Luo et al, ; Weng et al, ).…”