Polydopamine-Coated Poly(l-lactide) Nanofibers with Controlled Release of VEGF and BMP-2 as a Regenerative Periosteum

Abstract

The periosteum plays an important role in vascularization and ossification during bone repair. However, in most studies, an artificial periosteum cannot restore both functions of the periosteum concurrently. In this study, a novel nanofiber that can sustain the release of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) was fabricated to enhance the durability of angiogenesis and osteogenesis during bone regeneration. A cell-free tissue engineered periosteum based on an electrospinning poly-l-lactic acid (PLLA) nanofiber was fabricated, on which VEGF and BMP-2 were immobilized through a polydopamine (PDA) coating conveniently and safely (BVP@PLLA membrane). The results indicated a significantly improved loading rate as well as a slow and sustained release of VEGF and BMP-2 with the help of the PDA coating. BMP-2 immobilized on nanofibers successfully induced the osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) in vitro with high expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN), and alkaline phosphatase (ALP). Similarly, angiogenic differentiation of BMSCs with the expression of fetal liver kinase-1 (Flk-1) and vascular endothelial cadherin (VE-cadherin) was observed under the environment of VEGF sustained release. Moreover, an in vivo study revealed that the BVP@PLLA membrane could enhance vascular formation and new bone formation, which accelerates bone regeneration in rat femoral defects along with a massive periosteum defect. Therefore, our study suggests that the novel artificial periosteum with dual growth factor controlled release is a promising system to improve bone regeneration in bone defects along with a massive periosteum defect.

Electrospun nanofibers for bone regeneration: from biomimetic composition, structure to function

“…222 The results both in vitro and in vivo proved that this novel nanofibrous scaffold with dual growth factors promoted osteogenesis and angiogenesis concurrently, which further accelerated regeneration and vascular formation. 222 In order to better exert the effects of dual growth factors, Li et al developed a core–shell SF/PCL/PVA nanofibrous scaffold to control co-delivery of BMP-2 and CTGF by combining the technologies of coaxial electrospinning and layer-by-layer assembly. 67 CTGF was attached onto the surface of the nanofibers, thus demonstrating a transient release to exert a proangiogenic effect on bone healing.…”

Multipotential Role of Growth Factor Mimetic Peptides for Osteochondral Tissue Engineering

“…In a study by Laboy-López et al, a porous cellulose acetate fiber mat was developed using the electrospinning technique and the mats were chemically modified to bioactivate their surface by coupling adhesive osteogenic peptides such as KRSR, RGD and the growth factor BMP-2 to favor osteoconduction [71]. Sun et al fabricated a cell-free tissue-engineered periosteum based on an electrospinning poly-L-lactic acid (PLLA) nanofiber, where VEGF and BMP-2 were immobilized to enhance the durability of angiogenesis and osteogenesis during bone regeneration in bone with massive periosteum defect regeneration [72].…”

Coaxially Fabricated Dual‐Drug Loading Electrospinning Fibrous Mat with Programmed Releasing Behavior to Boost Vascularized Bone Regeneration

“…Traditional growth factors, like vascular endothelial growth factor (VEGF) and angiogenin (ANG) loaded in the drug delivery system have been widely applied in the field of tissue regeneration. [ 15 ] Usually high dosages of these compounds are used as angiogenesis promoters. However, it is worth noting that excessive exogenous growth factors may lead to pathological changes such as tumors.…”