Nanoscale perfluorocarbon expediates bone fracture healing through selectively activating osteoblastic differentiation and functions

Abstract

Background and rationale: Fracture incidence increases with ageing and other contingencies. However, the strategy of accelerating fracture repair in clinical therapeutics remain a huge challenge due to its complexity and a longlasting period. The emergence of nano-based drug delivery systems provides a highly efficient, targeted and controllable drug release at the diseased site. Thus far, fairly limited studies have been carried out using nanomedicines for the bone repair applications. Perfluorocarbon (PFC), FDA-approved clinical drug, is received increasing attention in nanomedicine due to its favorable chemical and biologic inertness, great biocompatibility, high oxygen affinity and serum-resistant capability. In the premise, the purpose of the current study is to prepare nano-sized PFC materials and to evaluate their advisable effects on promoting bone fracture repair.Results: Our data unveiled that nano-PFC significantly enhanced the fracture repair in the rabbit model with radial fractures, as evidenced by increased soft callus formation, collagen synthesis and accumulation of beneficial cytokines (e.g., vascular endothelial growth factor (VEGF), matrix metalloprotein 9 (MMP-9) and osteocalcin). Mechanistic studies unraveled that nano-PFC functioned to target osteoblasts by stimulating their differentiation and activities in bone formation, leading to accelerated bone remodeling in the fractured zones. Otherwise, osteoclasts were not affected upon nano-PFC treatment, ruling out the potential target of nano-PFC on osteoclasts and their progenitors. Conclusions:These results suggest that nano-PFC provides a potential perspective for selectively targeting osteoblast cell and facilitating callus generation. This study opens up a new avenue for nano-PFC as a promising agent in therapeutics to shorten healing time in treating bone fracture.

The Osteogenic Properties of Calcium Phosphate Cement Doped with Synthetic Materials: A Structured Narrative Review of Preclinical Evidence

“…It can dissolve oxygen, thus playing a crucial role in the delivery of oxygen for organ preservation [ 58 ]. Recent evidence reported the bone fracture healing properties of nanoscale perfluorocarbon in a rabbit model with radial fractures, as shown by the elevations in soft callus formation, collagen synthesis, as well as the expression of VEGF, MMP-9, and OCN [ 59 ]. Perfluoro-15-crown-5-ether (PFCE) is a commonly used perfluorocarbon, which is chemically and biologically inert, temperature and storage stable, as well as posing no infectious risk.…”

Oxygen-Generating Biomaterials for Translational Bone Regenerative Engineering

“…Consequently, PFCs promoted osteoblast differentiation and raised the levels of helpful cytokines, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9). 52 By enhancing dissolved oxygen dispersion through the matrix, systems incorporating PFCs can increase oxygenation but are not intended to serve as oxygen reservoirs. Although the improvement in effectual diffusivity is measurable, whether it reliably benefits cells remains to be determined.…”

“…Research on bone fractures in rabbits demonstrated that injection of a PFC nanoemulsion could accelerate bone regeneration under a hypoxic atmosphere by increasing the oxygen concentration at the fracture site. Consequently, PFCs promoted osteoblast differentiation and raised the levels of helpful cytokines, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) …”

Injectable nanofiber-reinforced bone cement with controlled biodegradability for minimally-invasive bone regeneration

“…Treatment of irregular bone defect and comminuted fracture, due to population aging, sports injury and traffic accident, remain as common clinical challenges. Due to the accumulating needs for faster healing after operation, the clinical demand for injectable biomaterials is increasing, which can allow for regeneration of diseased/injured bone tissue with minimally-invasive strategies [ [1] , [2] , [3] , [4] ]. Currently, poly (methyl methacrylate) (PMMA) is the most commonly used injectable material for bone supporting and pain relief after osteoporosis vertebral fracture [ [5] , [6] , [7] ].…”