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Triple Growth Factor Delivery Promotes Functional Bone Regeneration Following Composite Musculoskeletal Trauma

40 Pages Posted: 30 Nov 2020 Publication Status: Published

See all articles by Ramesh Subbiah

Ramesh Subbiah

Georgia Institute of Technology - George W. Woodruff School of Mechanical Engineering

Marissa Ruehle

Georgia Institute of Technology - Parker H. Petit Institute for Bioengineering and Bioscience

Brett S. Klosterhoff

Georgia Institute of Technology - George W. Woodruff School of Mechanical Engineering

Angela SP Lin

University of Oregon - Knight Campus for Accelerating Scientific Impact

Marian H. Hettiaratchi

University of Oregon - Knight Campus for Accelerating Scientific Impact

Nick J. Willett

Georgia Institute of Technology - Parker H. Petit Institute for Bioengineering and Bioscience

Luiz E. Bertassoni

Oregon Health and Science University - Division of Biomaterials and Biomechanics

Andrés J. García

Georgia Institute of Technology - Parker H. Petit Institute for Bioengineering and Bioscience; Georgia Institute of Technology - George W. Woodruff School of Mechanical Engineering

Robert E. Guldberg

Georgia Institute of Technology - George W. Woodruff School of Mechanical Engineering

Abstract

Type III fractures typically involve segmental bone loss with extensive adjacent soft tissue injury to muscle and vasculature. Such severe composite injuries to bone and muscle often require multiple treatment procedures and are associated with significantly higher rates of complications, including non-union, infection, prolonged disability, and amputation. Successful bone healing depends on early re-vascularization to restore oxygen, nutrient, growth factor, and progenitor cell supply to the injury.  Therapeutic angiogenesis strategies have therefore been investigated to promote re-vascularization following severe bone injuries, however results have been inconsistent.  In this study, co-stimulation of microvascular fragment constructs with vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) promoted vascular network formation in vitro compared to VEGF or PDGF alone. In an in vivo model of segmental bone and volumetric muscle loss injury, combined delivery of VEGF and PDGF with a low dose of bone morphogenetic protein-2 (BMP-2) significantly enhanced regeneration of vascularized bone compared to BMP-2 treatment alone. This study demonstrates the potential for a combined osteoinductive and angiogenic growth factor delivery strategy to promote functional bone regeneration following severe composite musculoskeletal injury.

Keywords: open fracture; volumetric muscle loss; angiogenesis; bone regeneration; growth factors; delivery system; segmental bone defect

Suggested Citation

Subbiah, Ramesh and Ruehle, Marissa and Klosterhoff, Brett S. and Lin, Angela SP and Hettiaratchi, Marian H. and Willett, Nick J. and Bertassoni, Luiz E. and García, Andrés J. and Guldberg, Robert E., Triple Growth Factor Delivery Promotes Functional Bone Regeneration Following Composite Musculoskeletal Trauma. Available at SSRN: https://ssrn.com/abstract=3737321 or http://dx.doi.org/10.2139/ssrn.3737321

Ramesh Subbiah (Contact Author)

Georgia Institute of Technology - George W. Woodruff School of Mechanical Engineering

801 Ferst Drive
Georgia Institute of Technology
Atlanta, GA 30332-0405
United States

Marissa Ruehle

Georgia Institute of Technology - Parker H. Petit Institute for Bioengineering and Bioscience ( email )

Atlanta, GA 30332
United States

Brett S. Klosterhoff

Georgia Institute of Technology - George W. Woodruff School of Mechanical Engineering ( email )

801 Ferst Drive
Georgia Institute of Technology
Atlanta, GA 30332-0405
United States

Angela SP Lin

University of Oregon - Knight Campus for Accelerating Scientific Impact ( email )

Eugene, OR
United States

Marian H. Hettiaratchi

University of Oregon - Knight Campus for Accelerating Scientific Impact ( email )

Eugene, OR
United States

Nick J. Willett

Georgia Institute of Technology - Parker H. Petit Institute for Bioengineering and Bioscience ( email )

Atlanta, GA 30332
United States

Luiz E. Bertassoni

Oregon Health and Science University - Division of Biomaterials and Biomechanics ( email )

Portland, OR
United States

Andrés J. García

Georgia Institute of Technology - Parker H. Petit Institute for Bioengineering and Bioscience ( email )

Atlanta, GA 30332
United States

Georgia Institute of Technology - George W. Woodruff School of Mechanical Engineering ( email )

801 Ferst Drive
Georgia Institute of Technology
Atlanta, GA 30332-0405
United States

Robert E. Guldberg

Georgia Institute of Technology - George W. Woodruff School of Mechanical Engineering ( email )

801 Ferst Drive
Georgia Institute of Technology
Atlanta, GA 30332-0405
United States

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