Bone regeneration by bone morphogenetic protein-2 from porous beads with leaf-stacked structure for critical-sized femur defect model in dogs

Abstract

The objective of this study was to investigate whether porous beads with a leaf-stacked scaffold loaded with bone morphogenetic protein-2, with sustained release for up to four weeks, were beneficial to a dog model of critical long bone defects and capable of promoting bone regeneration without side effects. Critical long bone defects were created in the femoral diaphyses of 21 dogs. Each critical defect was fixed with an intramedullary pin and an universal locking plate. Leaf-stacked scaffold beads were implanted into the defect, which was covered with a membrane. Nineteen samples were evaluated 4, 8, and 12 weeks after surgery using simple radiographs, serum chemistry measurements, histological staining, and gene expression analysis. Sustained bone morphogenetic protein-2 release from the leafstacked scaffold continued for four weeks and consistently affected the expression of early and late osteogenesis factors. The results suggest that sustained bone morphogenetic protein-2 release is effective for bone regeneration, with minimal side effects.

Scaffold Guided Bone Regeneration for the Treatment of Large Segmental Defects in Long Bones

“…In addition, the effective and safe delivery of growth factors, such as BMP-2 [211,216,217,236] and VEGF [237,238], has been tested over the last 4 years in large animal models. For example, a rather complex strategy, using an in vivo bioreactor approach to pre-vascularize a 3D-printed BMP-2-loaded scaffold before implantation into a 5 cm segmental defect in the ovine tibia, was tested and found to be feasible [216].…”

“…In another study, a 3D printed polymer/ceramic composite scaffold was successfully combined with a rhBMP-2-loaded collagen sponge to bridge a critical size defect (5 cm) in a sheep metatarsus fracture model (intramedullary nail stabilization) [217]. Two different groups studied PCL/beta-TCP scaffolds or porous beads as carrier materials for the release of BMP-2 in dogs [211,236]. Cell-based approaches have been increasingly tested in vivo in large animal models, comprising cord blood cells [209], osteoprogenitors [218], mesenchymal stromal cells [207,214,239,240], periosteum-derived stem cells [215] but also blood [208] or platelet-rich fibrin exudate [241].…”

Pre-Clinical Evaluation of Biological Bone Substitute Materials for Application in Highly Loaded Skeletal Sites

“…The addition of cells to BSMs is generally performed by seeding the material with the patient's own (osteogenic stem) cells (e.g., obtained via bone marrow aspiration) [61][62][63][64][65][66] prior to or during surgical bone defect repair [67]. In addition to cell-based bone regeneration strategies, growth factors such as bone morphogenic proteins (e.g., BMP-2 and BMP-7) [63,[68][69][70][71], transforming growth factor beta (TGF-β) [72], insulin-like growth factor (IGF-1), platelet-derived growth factor (PDGF) [73], or vascular endothelial growth factor (VEGF), have also been proposed. Some growth factors provide osteoinductivity, which enhances bone regeneration [56].…”