Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo

Zhenxing Shao, Xin Zhang, Yanbin Pi, Xiaokun Wang, Zhuqing Jia, Jingxian Zhu, Linghui Dai, Wenqing Chen, Ling Yin, Haifeng Chen, Chunyan Zhou, Yingfang Ao

Research output: Contribution to journalArticle

Abstract

Mesenchymal stem cell (MSC) is a promising cell source candidate in tissue engineering (TE) and regenerative medicine. However, the inability to target MSCs in tissues of interest with high efficiency and engraftment has become a significant barrier for MSC-based therapies. The mobilization and transfer of MSCs to defective/damaged sites in tissues or organs in vivo with high efficacy and efficiency has been a major concern. In the present study, we identified a peptide sequence (E7) with seven amino acids through phage display technology, which has a high specific affinity to bone marrow-derived MSCs. Subsequent analysis suggested that the peptide could effi{ligature}ciently interact specifi{ligature}cally with MSCs without any species specificity. Thereafter, E7 was covalently conjugated onto polycaprolactone (PCL) electrospun meshes to construct an " MSC-homing device" for the recruitment of MSCs both in vitro and in vivo. The E7-conjugated PCL electrospun meshes were implanted into a cartilage defect site of rat knee joints, combined with a microfracture procedure to mobilize the endogenous MSCs. After 7 d of implantation, immunofluorescence staining showed that the cells grown into the E7-conjugated PCL electrospun meshes yielded a high positive rate for specific MSC surface markers (CD44, CD90, and CD105) compared with those in arginine-glycine-aspartic acid (RGD)-conjugated PCL electrospun meshes (63.67% vs. 3.03%; 59.37% vs. 2.98%; and 61.45% vs. 3.82%, respectively). Furthermore, the percentage of CD68 positive cells in the E7-conjugated PCL electrospun meshes was much lower than that in the RGD-conjugated PCL electrospun meshes (5.57% vs. 53.43%). This result indicates that E7-conjugated PCL electrospun meshes absorb much less inflammatory cells in vivo than RGD-conjugated PCL electrospun meshes. The results of the present study suggest that the identified E7 peptide sequence has a high specific affinity to MSCs. Covalently conjugating this peptide on the synthetic PCL mesh significantly enhanced the MSC recruitment of PCL in vivo. This method provides a wide range of potential applications in TE.

Original languageEnglish (US)
Pages (from-to)3375-3387
Number of pages13
JournalBiomaterials
Volume33
Issue number12
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

Fingerprint

Polycaprolactone
Stem cells
Mesenchymal Stromal Cells
Peptides
Tissue Engineering
Tissue engineering
Ligation
Amino acids
Cells
polycaprolactone
Tissue
Species Specificity
Stress Fractures
Arginine
Bacteriophages
Regenerative Medicine
Bioelectric potentials
Cartilage
Cell- and Tissue-Based Therapy
Knee Joint

Keywords

  • MSC-homing
  • Peptide-modified polycaprolactone electrospun mesh
  • Phage display
  • Tissue engineering (TE)

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo. / Shao, Zhenxing; Zhang, Xin; Pi, Yanbin; Wang, Xiaokun; Jia, Zhuqing; Zhu, Jingxian; Dai, Linghui; Chen, Wenqing; Yin, Ling; Chen, Haifeng; Zhou, Chunyan; Ao, Yingfang.

In: Biomaterials, Vol. 33, No. 12, 01.04.2012, p. 3375-3387.

Research output: Contribution to journalArticle

Shao, Z, Zhang, X, Pi, Y, Wang, X, Jia, Z, Zhu, J, Dai, L, Chen, W, Yin, L, Chen, H, Zhou, C & Ao, Y 2012, 'Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo', Biomaterials, vol. 33, no. 12, pp. 3375-3387. https://doi.org/10.1016/j.biomaterials.2012.01.033
Shao, Zhenxing ; Zhang, Xin ; Pi, Yanbin ; Wang, Xiaokun ; Jia, Zhuqing ; Zhu, Jingxian ; Dai, Linghui ; Chen, Wenqing ; Yin, Ling ; Chen, Haifeng ; Zhou, Chunyan ; Ao, Yingfang. / Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo. In: Biomaterials. 2012 ; Vol. 33, No. 12. pp. 3375-3387.
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AU - Shao, Zhenxing

AU - Zhang, Xin

AU - Pi, Yanbin

AU - Wang, Xiaokun

AU - Jia, Zhuqing

AU - Zhu, Jingxian

AU - Dai, Linghui

AU - Chen, Wenqing

AU - Yin, Ling

AU - Chen, Haifeng

AU - Zhou, Chunyan

AU - Ao, Yingfang

PY - 2012/4/1

Y1 - 2012/4/1

N2 - Mesenchymal stem cell (MSC) is a promising cell source candidate in tissue engineering (TE) and regenerative medicine. However, the inability to target MSCs in tissues of interest with high efficiency and engraftment has become a significant barrier for MSC-based therapies. The mobilization and transfer of MSCs to defective/damaged sites in tissues or organs in vivo with high efficacy and efficiency has been a major concern. In the present study, we identified a peptide sequence (E7) with seven amino acids through phage display technology, which has a high specific affinity to bone marrow-derived MSCs. Subsequent analysis suggested that the peptide could effi{ligature}ciently interact specifi{ligature}cally with MSCs without any species specificity. Thereafter, E7 was covalently conjugated onto polycaprolactone (PCL) electrospun meshes to construct an " MSC-homing device" for the recruitment of MSCs both in vitro and in vivo. The E7-conjugated PCL electrospun meshes were implanted into a cartilage defect site of rat knee joints, combined with a microfracture procedure to mobilize the endogenous MSCs. After 7 d of implantation, immunofluorescence staining showed that the cells grown into the E7-conjugated PCL electrospun meshes yielded a high positive rate for specific MSC surface markers (CD44, CD90, and CD105) compared with those in arginine-glycine-aspartic acid (RGD)-conjugated PCL electrospun meshes (63.67% vs. 3.03%; 59.37% vs. 2.98%; and 61.45% vs. 3.82%, respectively). Furthermore, the percentage of CD68 positive cells in the E7-conjugated PCL electrospun meshes was much lower than that in the RGD-conjugated PCL electrospun meshes (5.57% vs. 53.43%). This result indicates that E7-conjugated PCL electrospun meshes absorb much less inflammatory cells in vivo than RGD-conjugated PCL electrospun meshes. The results of the present study suggest that the identified E7 peptide sequence has a high specific affinity to MSCs. Covalently conjugating this peptide on the synthetic PCL mesh significantly enhanced the MSC recruitment of PCL in vivo. This method provides a wide range of potential applications in TE.

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KW - MSC-homing

KW - Peptide-modified polycaprolactone electrospun mesh

KW - Phage display

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