Abstract
Recently, it has been shown that tethered anti-BMP2 monoclonal antibodies (mAbs) can trap BMP ligands and thus provide BMP inductive signals for osteo-differentiation of progenitor cells. The objectives of this study were to: (1) develop a co-delivery system based on murine anti-BMP2 mAb-loaded alginate microspheres encapsulating human bone marrow mesenchymal stem cells (hBMMSCs); and (2) investigate osteogenic differentiation of encapsulated stem cells in alginate microspheres invitro and invivo. Alginate microspheres of 1±0.1mm diameter were fabricated with 2×106 hBMMSCs per mL of alginate. Critical-size calvarial defects (5mm diameter) were created in immune-compromised mice and alginate microspheres preloaded with anti-BMP mAb encapsulating hBMMSCs were transplanted into defect sites. Alginate microspheres pre-loaded with isotype-matched non-specific antibody were used as the negative control. After 8 weeks, micro CT and histologic analyses were used to analyze bone formation. Invitro analysis demonstrated that anti-BMP2 mAbs tethered BMP2 ligands that can activate the BMP receptors on hBMMSCs. The co-delivery system described herein, significantly enhanced hBMMSC-mediated osteogenesis, as confirmed by the presence of BMP signal pathway-activated osteoblast determinants Runx2 and ALP. Our results highlight the importance of engineering the microenvironment for stem cells, and particularly the value of presenting inductive signals for osteo-differentiation of hBMMSCs by tethering BMP ligands using mAbs. This strategy of engineering the microenvironment with captured BMP signals is a promising modality for repair and regeneration of craniofacial, axial and appendicular bone defects.
Original language | English |
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Pages (from-to) | 6572-6579 |
Number of pages | 8 |
Journal | Biomaterials |
Volume | 34 |
Issue number | 28 |
DOIs | |
Publication status | Published - Sep 2013 |
Externally published | Yes |
Keywords
- Alginate hydrogel
- Anti-BMP2 monoclonal antibodies
- Cells encapsulation
- Mesenchymal stem cell-mediated bone regeneration
ASJC Scopus subject areas
- Bioengineering
- Ceramics and Composites
- Biophysics
- Biomaterials
- Mechanics of Materials