Bone regeneration using photocrosslinked hydrogel incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles

Autor: Keith M. McLean, Changsheng Liu, Veronica Glattauer, Jing Wang, Lingyan Cao, Jerome A. Werkmeister
Rok vydání: 2014
Předmět:
Male
Bone Regeneration
Materials science
Compressive Strength
Light
Cell Survival
medicine.medical_treatment
Composite number
Biophysics
Bone Morphogenetic Protein 2
Nanoparticle
Biocompatible Materials
Bioengineering
Choristoma
Hydrogel
Polyethylene Glycol Dimethacrylate
Biomaterials
Mice
Calcification
Physiologic
Osteogenesis
Transforming Growth Factor beta
In vivo
Cell Adhesion
medicine
Animals
Humans
Viability assay
Bone regeneration
Chitosan
Muscles
Growth factor
technology
industry
and agriculture
Spectrometry
X-Ray Emission
Coculture Techniques
Recombinant Proteins
Biomechanical Phenomena
Radiography
Kinetics
Cross-Linking Reagents
Mechanics of Materials
Self-healing hydrogels
Ceramics and Composites
Nanoparticles
Alkaline phosphatase
Diaphyses
Rabbits
Stress
Mechanical
Biomedical engineering
Zdroj: Biomaterials. 35:2730-2742
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2013.12.028
Popis: Although rhBMP-2 has excellent ability to accelerate the repair of normal bone defects, limitations of its application exist in the high cost and potential side effects. This study aimed to develop a composite photopolymerisable hydrogel incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles (PH/rhBMP-2/NPs) as the bone substitute to realize segmental bone defect repair at a low growth factor dose. Firstly rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles (rhBMP-2/NPs) were prepared and characterized by DLS and TEM. Composite materials, PH/rhBMP-2/NPs were developed and investigated by SEM-EDS as well as a series of physical characterizations. Using hMSCs as an in vitro cell model, composite photopolymerisable hydrogels incorporating NPs (PH/NPs) showed good cell viability, cell adhesion and time dependent cell ingrowth. In vitro release kinetics of rhBMP-2 showed a significantly lower initial burst release from the composite system compared with the growth factor-loaded particles alone or encapsulated directly within the hydrogel, followed by a slow release over time. The bioactivity of released rhBMP-2 was validated by alkaline phosphatase (ALP) activity as well as a mineralization assay. In in vivo studies, the PH/rhBMP-2/NPs induced ectopic bone formation in the mouse thigh. In addition, we further investigated the in vivo effects of rhBMP-2-loaded scaffolds in a rabbit radius critical defect by three dimensional micro-computed tomographic (μCT) imaging, histological analysis, and biomechanical measurements. Animals implanted with the composite hydrogel containing rhBMP-2-loaded nanoparticles underwent gradual resorption with more pronounced replacement by new bone and induced reunion of the bone marrow cavity at 12 weeks, compared with animals implanted with hydrogel encapsulated growth factors alone. These data provided strong evidence that the composite PH/rhBMP-2/NPs are a promising substitute for bone tissue engineering.
Databáze: OpenAIRE
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