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Nanofiber/Microsphere Hybrid Matrices In Vivo for Bone Regenerative Engineering: A Preliminary Report

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Abstract

The demand for bone grafts has led to advances in regenerative engineering, a field at the intersection of advanced biomaterials, stem cell science, physics, developmental biology, and clinical translation. In this work, the authors evaluated a hybrid nanofiber/microsphere matrix both in vitro and in vivo for its ability to promote bone regeneration. Quantitative measures of cellular characteristics in vitro showed a higher fraction of marrow stromal cells with collagen promoter activity on hybrid matrices compared to control matrices (41 vs. 24%, p = 0.02). Control and hybrid matrices were then implanted for 6 weeks in calvarial defects of mice, and the animals received a single injection of calcein 1 day prior to sacrifice to visualize bone formation. Cryohistology of the undecalfied implants were evaluated for markers of bone mineralization, which revealed the evidence of higher levels of bone tissue formation in hybrid matrices compared to controls. These data provide support that nanofiber-permeated, sintered, composite microsphere matrices may be a particularly useful matrix for the regenerative engineering of bone.

Lay Summary

One idea to regenerate bone is to mimic the structure, composition, and feature size of natural human bone in a synthetic matrix to guide human stem cells. In this work, the authors combine an advanced material matrix with special genetically engineered stem cells to investigate if the special composition of the matrix can help improve existing matrices to support the regeneration of human bone. These results show that while the new matrices support a smaller population of cells, those cells are more likely to show evidence of growing into cells that may create bone.

Future Work

Future studies will include the implantation of transgenic, cell-seeded matrices of one fluorescent reporter mouse implanted in a host mouse that contains a separate fluorophore with a similar promoter. These studies will allow determination of the source of bone formation in these models: from host or from implant.

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Acknowledgements

The authors wish a special thanks to Nat Dyment and Max Villa for their help with Fiji and development of macros for fractional area measurements.

Funding

The authors wish to thank the Department of Defense for their sponsorship through grant DAMD W81XWH11-10262.

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Authors and Affiliations

  1. The Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, Institute for Regenerative Engineering, School of Medicine, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT, 06030-3711, USA

    Clarke Nelson, Yusuf Khan & Cato T. Laurencin

  2. Department of Orthopaedic Surgery, School of Medicine, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT, 06030-3711, USA

    Yusuf Khan & Cato T. Laurencin

  3. Department of Materials Science and Engineering, School of Engineering, University of Connecticut, Storrs, CT, 06268, USA

    Yusuf Khan

  4. Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA

    Cato T. Laurencin

Authors
  1. Clarke Nelson
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  2. Yusuf Khan
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  3. Cato T. Laurencin
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Corresponding author

Correspondence to Cato T. Laurencin.

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All animal studies were accomplished in compliance with the Institutional Animal Care and Use Committee at the University of Connecticut Health Center.

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Nelson, C., Khan, Y. & Laurencin, C.T. Nanofiber/Microsphere Hybrid Matrices In Vivo for Bone Regenerative Engineering: A Preliminary Report. Regen. Eng. Transl. Med. 4, 133–141 (2018). https://doi.org/10.1007/s40883-018-0055-1

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  • DOI: https://doi.org/10.1007/s40883-018-0055-1

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