PLGA-linked alendronate enhances bone repair in diaphysis defect model

Abstract

Alendronate (ALN) is known as an anti-resorptive drug for the treatment of osteoporosis. Recently, ALN was found to stimulate osteogenic differentiation in mesenchymal stem cells and enhance new bone formation in calvarial bone defects. Previous in vitro and in vivo studies found that the effective concentration of ALN was approximately 1-10 μm. In the present study, a poly (lactic-co-glycolic acid) (PLGA) cross-linked ALN (PLGA-ALN) with a short-term controlled-release property for local application to enhance bone repair was developed. An in vitro drug-release kinetic test showed that PLGA-ALN microspheres released an effective concentration (50-100 nm) of ALN for 9 days. The effect of PLGA-ALN on bone repair was tested in a rat femoral bone defect model. The biomechanical study results showed that the maximal strength, stiffness and energy absorption were significantly increased in the PLGA-ALN group compared with the PLGA group. The microstructure of the newly formed bone at the defect site was analysed using microcomputed tomography. The PLGA-ALN group significantly improved the trabecular bone volume at the defect site compared with the PLGA group. The fibril collagen and immunolocalized bone morphogenetic protein 2 were evident in the newly formed trabecular bone in the PLGA-ALN group. Local use of newly developed PLGA-ALN-enhanced bone repair was attributable to increasing bone matrix formation, which improved the ultrastructure of the newly formed bone and thus increased the biomechanical properties of the repaired bone. It is suggested that PLGA-ALN may be a potential bone graft substitute to enhance bone repair. Copyright © 2016 John Wiley & Sons, Ltd.

Green Tea Catechin (-)-Epigallocatechin-3-Gallate (EGCG) Facilitates Fracture Healing

“…Percutaneous local injection of either vehicle or EGCG were given locally and daily 2 days after the fracture creation for 2 weeks (n = 14 at each group). Micro-computed tomography (µ-CT), biomechanical analysis (n = 7 at each group), and histological study (n = 7 at each group) were done 2 and 4 weeks after treatment [19][20][21].…”

Bisphosphonate‐Functionalized Scaffolds for Enhanced Bone Regeneration

“…The composite microsphere made from carboxylated PLGA and BPs showed good local sustained release in bone defects ( Figure A,B). This PLGA/ALN system promoted bone formation and improved the quality of repaired bone (Figure C–E) …”

“…ALN‐linked PLGA microsphere enhance bone repair . A) SEM images of ALN‐linked PLGA (left image, scale bar = 100 µm; right image, scale bar = 50 µm).…”

“…Black arrows highlight osteoblasts located in the lacunae of regenerated bone. Reproduced with permission . Copyright 2017, John Wiley & Sons, Inc.…”

Development of nanomaterials for bone-targeted drug delivery

“…PLGA nanoparticles can also be used for the delivery of bone-related hormones and proteins, such as parathyroid hormone (PTH) [74] and BMP-2 [75], by providing protection against enzymatic degradation in vivo and improving diffusion across biological carriers [76]. PLGA nanoparticles can also reduce the systemic adverse effects associated with the administration of antiresorptive drugs, such as Alen, through controlled delivery of small doses at the site of administration [77]. The rate of drug release from PLGA nanoparticles can also be regulated by controlling the co-polymer ratio between lactide and glycolide, and the molecular weight of the polymer [72].…”