ArticlePloS one2013
Trehalose maintains bioactivity and promotes sustained release of BMP-2 from lyophilized CDHA scaffolds for enhanced osteogenesis in vitro and in vivo.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- International multisite implementation of distributed cell-free protein biomanufacturing to advance health and research equity.Science advances · 2026Article
- Applications of recombinant type III collagen in tissue engineering.Biomedical engineering online · 2025Review
- Oral trehalose improves histological and behavior symptoms of mucopolysaccharidosis type II in iduronate 2-sulfatase deficient mice.Scientific reports · 2025Article
- A novel cryopreservation solution for adipose tissue based on metformin.Stem cell research & therapy · 2025Article
- Article
- Active bone material containing modified recombinant human bone morphogenetic protein-2 induces bone regeneration in rabbit spina bifida.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Enhanced Biocompatibility and Osteogenic Activity of Marine-Plankton-Derived Whitlockite Bone Granules through Bone Morphogenetic Protein 2 Incorporation.Bioengineering (Basel, Switzerland) · 2022Article
- The combination of trehalose and glycerol: an effective and non-toxic recipe for cryopreservation of human adipose-derived stem cells.Stem cell research & therapy · 2020Article
- Porous PolyHIPE microspheres for protein delivery from an injectable bone graft.Acta biomaterialia · 2019Article
- Stabilization of enzyme-immobilized hydrogels for extended hypoxic cell culture.Emergent materials · 2019Article
- Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose.International journal of nanomedicine · 2018Article
- Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles.International journal of pharmaceutics · 2016Article
- Article
- Successful cryopreservation of whole sheep ovary by using DMSO-free cryoprotectant.Journal of assisted reproduction and genetics · 2015Article
- Rapid bone regeneration by Escherichia coli-derived recombinant human bone morphogenetic protein-2 loaded on a hydroxyapatite carrier in the rabbit calvarial defect model.Biomaterials research · 2015Article
- Article
- Trehalose maintains vitality of mouse epididymal epithelial cells and mediates gene transfer.PloS one · 2014Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcium phosphate (Ca-P) scaffolds have been widely employed as a supportive matrix and delivery system for bone tissue engineering. Previous studies using osteoinductive growth factors loaded Ca-P scaffolds via passive adsorption often experience issues associated with easy inactivation and uncontrolled release. In present study, a new delivery system was fabricated using bone morphogenetic protein-2 (BMP-2) loaded calcium-deficient hydroxyapatite (CDHA) scaffold by lyophilization with addition of trehalose. The in vitro osteogenesis effects of this formulation were compared with lyophilized BMP-2/CDHA construct without trehalose and absorbed BMP-2/CDHA constructs with or without trehalose. The release characteristics and alkaline phosphatase (ALP) activity analyses showed that addition of trehalose could sufficiently protect BMP-2 bioactivity during lyophilization and achieve sustained BMP-2 release from lyophilized CDHA construct in vitro and in vivo. However, absorbed BMP-2/CDHA constructs with or without trehalose showed similar BMP-2 bioactivity and presented a burst release. Quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that lyophilized BMP-2/CDHA construct with trehalose (lyo-tre-BMP-2) promoted osteogenic differentiation of bone marrow stromal cells (bMSCs) significantly and this formulation could preserve over 70% protein bioactivity after 5 weeks storage at 25°C. Micro-computed tomography, histological and fluorescent labeling analyses further demonstrated that lyo-tre-BMP-2 formulation combined with bMSCs led to the most percentage of new bone volume (38.79% ± 5.32%) and area (40.71% ± 7.14%) as well as the most percentage of fluorochrome stained bone area (alizarin red S: 2.64% ± 0.44%, calcein: 6.08% ± 1.37%) and mineral apposition rate (4.13 ± 0.62 µm/day) in critical-sized rat cranial defects healing. Biomechanical tests also indicated the maximum stiffness (118.17 ± 15.02 Mpa) and load of fracture (144.67 ± 16.13 N). These results lay a potential framework for future study by using trehalose to preserve growth factor bioactivity and optimize release profile of Ca-P based delivery system for enhanced bone regeneration.
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