, Volume 471, Issue 3, pp 721-726
Date: 21 Nov 2012

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

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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.

The institution of one of the authors (DSWB) has received, during the study period, funding from Orthopaedic Research and Education Foundation/Musculoskeletal Transplant Foundation (OREF/MTF), and the Rochester/Finger Lakes Eye & Tissue Bank (RETB/FLETB). The institution of one the authors (MH) has received, during the study period, funding from the NIH (T32 Training in Orthopaedic Research (NIH-AR053459)).
All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.
Clinical Orthopaedics and Related Research neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use.
Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.
This work was performed at the University of Rochester, Rochester, NY, USA