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Neonatal Fibrin Scaffolds Promote Enhanced Cell Adhesion, Migration, and Wound Healing In Vivo Compared to Adult Fibrin Scaffolds

  • 2020 CMBE Young Innovators Issue
  • Published:
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Abstract

Introduction

Fibrin scaffolds are often utilized to treat chronic wounds. The monomer fibrinogen used to create such scaffolds is typically derived from adult human or porcine plasma. However, our previous studies have identified extensive differences in fibrin network properties between adults and neonates, including higher fiber alignment in neonatal networks. Wound healing outcomes have been linked to fibrin matrix structure, including fiber alignment, which can affect the binding and migration of cells. We hypothesized that fibrin scaffolds derived from neonatal fibrin would enhance wound healing outcomes compared to adult fibrin scaffolds.

Methods

Fibrin scaffolds were formed from purified adult or neonatal fibrinogen and thrombin then structural analysis was conducted via confocal microscopy. Human neonatal dermal fibroblast attachment, migration, and morphology on fibrin scaffolds were assessed. A murine full thickness injury model was used to compare healing in vivo in the presence of neonatal fibrin, adult fibrin, or saline.

Results

Distinct fibrin architectures were observed between adult and neonatal scaffolds. Significantly higher fibroblast attachment and migration was observed on neonatal scaffolds compared to adults. Cell morphology on neonatal scaffolds exhibited higher spreading compared to adult scaffolds. In vivo significantly smaller wound areas and greater epidermal thickness were observed when wounds were treated with neonatal fibrin compared to adult fibrin or a saline control.

Conclusions

Distinctions in neonatal and adult fibrin scaffold properties influence cellular behavior and wound healing. These studies indicate that fibrin scaffolds sourced from neonatal plasma could improve healing outcomes compared to scaffolds sourced from adult plasma.

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Acknowledgments

Funding for this project was provide by start-up funds for Ashley Brown from North Carolina State University, DMR-1847488 from the National Science Foundation, and CDMRP W81XWH-15-1-0485 from the U.S. Department of Defense. The authors would like to thank Eva Johannes, PhD, Director at the Cellular and Molecular Imaging Facility at North Carolina State University for technical assistance with microscopy, Nina Guzzetta, M.D. from Children’s Healthcare of Atlanta and Emory University for providing neonatal plasma samples, and Lucas Timmins, PhD from University of Utah for assistance with Matlab code.

Conflict of interest

Kimberly Nellenbach, Seema Nandi, Christopher Peeler, Alexander Kyu, and Ashley C. Brown declare that they have no conflicts of interest.

Ethical Approval

All human subjects research was carried out in accordance with Department of Health and Human Services policy and regulations and approved by the Emory University IRB. All animal studies were carried out in accordance with North Carolina State University policies and regulations including meeting standards and guidelines set forth by the NIH Guide for the Care and Use of Laboratory Animals. All animal studies were approved by the North Carolina State University IACUC.

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Authors and Affiliations

  1. Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Raleigh, NC, 27695, USA

    Kimberly Nellenbach, Seema Nandi, Christopher Peeler, Alexander Kyu & Ashley C. Brown

  2. Comparative Medicine Institute, North Carolina State University, Raleigh, NC, 27695, USA

    Kimberly Nellenbach, Seema Nandi & Ashley C. Brown

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  1. Kimberly Nellenbach
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  2. Seema Nandi
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Correspondence to Ashley C. Brown.

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Nellenbach, K., Nandi, S., Peeler, C. et al. Neonatal Fibrin Scaffolds Promote Enhanced Cell Adhesion, Migration, and Wound Healing In Vivo Compared to Adult Fibrin Scaffolds. Cel. Mol. Bioeng. 13, 393–404 (2020). https://doi.org/10.1007/s12195-020-00620-5

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