Co-encapsulation of anti-BMP2 monoclonal antibody and mesenchymal stem cells in alginate microspheres for bone tissue engineering

Alireza Moshaverinia, Sahar Ansari, Chider Chen, Xingtian Xu, Kentaro Akiyama, Malcolm L. Snead, Homayoun H. Zadeh, Songtao Shi

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84 Citations (Scopus)

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 languageEnglish
Pages (from-to)6572-6579
Number of pages8
JournalBiomaterials
Volume34
Issue number28
DOIs
Publication statusPublished - Sep 1 2013
Externally publishedYes

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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

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