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Int. J. Mol. Sci. 2015, 16(5), 11785-11803; doi:10.3390/ijms160511785

Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix

1
Division of Biomedical Engineering Research Institute, National Defense Medical College, Saitama 359-8513, Japan
2
Research Support Center, Dokkyo Medical University, Tochigi 321-0293, Japan
3
Department of Medical Engineering, National Defense Medical College, Saitama 359-8513, Japan
4
Department of Surgery, Tokorozawa Meisei Hospital, Saitama 359-1145, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Mohamed N. Rahaman
Received: 11 March 2015 / Revised: 7 May 2015 / Accepted: 15 May 2015 / Published: 22 May 2015
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
View Full-Text   |   Download PDF [3920 KB, uploaded 22 May 2015]   |  

Abstract

Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm–3 μm in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures. View Full-Text
Keywords: adipose-derived stromal cells; bone marrow-derived mesenchymal stem cells; nano/micro particles; coating matrix; cell delivery systems adipose-derived stromal cells; bone marrow-derived mesenchymal stem cells; nano/micro particles; coating matrix; cell delivery systems
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ishihara, M.; Kishimoto, S.; Takikawa, M.; Hattori, H.; Nakamura, S.; Shimizu, M. Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix. Int. J. Mol. Sci. 2015, 16, 11785-11803.

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