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Published in: Clinical Orthopaedics and Related Research® 3/2013

01-03-2013 | Emerging Ideas

Emerging Ideas: Engineering the Periosteum: Revitalizing Allografts by Mimicking Autograft Healing

Authors: Michael D. Hoffman, MS, Danielle S. W. Benoit, PhD

Published in: Clinical Orthopaedics and Related Research® | Issue 3/2013

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Abstract

Background

To fulfill the need for large volumes, devitalized allografts are used to treat massive bone defects despite a 60%, 10-year postimplantation fracture rate. Allograft healing is inferior to autografts where the periosteum orchestrates remodeling.

Hypothesis

By augmenting allografts with a tissue engineered periosteum consisting of tunable and degradable, poly(ethylene glycol) (PEG) hydrogels for mesenchymal stem cell (MSC) transplantation, the functions critical for periosteum-mediated healing will be identified and emulated.

Method of Study

PEG hydrogels will be designed to emulate periosteum-mediated autograft healing to revitalize allografts. We will exploit murine femoral defect models for these approaches. Critical-sized, 5-mm segmental defects will be created and filled with decellularized allograft controls or live autograft controls. Alternatively, defects will be treated with our experimental approaches: decellularized allografts coated with MSCs transplanted via degradable PEG hydrogels to mimic progenitor cell densities and persistence during autograft healing. Healing will be evaluated for 9 weeks using microcomputed tomography, mechanical testing, and histologic analysis. If promising, MSC densities, hydrogel compositions, and genetic methods will be used to isolate critical aspects of engineered periosteum that modulate healing. Finally, hydrogel biochemical characteristics will be altered to initiate MSC and/or host-material interactions to further promote remodeling of allografts.

Significance

This approach represents a novel tissue engineering strategy whereby degradable, synthetic hydrogels will be exploited to emulate the periosteum. The microenvironment, which will mediate MSC transplantation, will use tunable PEG hydrogels for isolation of critical allograft revitalization factors. In addition, hydrogels will be modified with biochemical cues to further augment allografts to reduce or eliminate revision surgeries associated with allograft failures.
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Metadata
Title
Emerging Ideas: Engineering the Periosteum: Revitalizing Allografts by Mimicking Autograft Healing
Authors
Michael D. Hoffman, MS
Danielle S. W. Benoit, PhD
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
Clinical Orthopaedics and Related Research® / Issue 3/2013
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-012-2695-7

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