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Turning Fat into Bone

Brian C. Werner, MD 2011 MTF/Charles H. Herndon Resident Clincian Scientist Training Grant
Research Summary

Research topic: Investigating the ability of human adipose tissue stem cells to create a bone allograft 

Research results: Found that R1 osteotropic peptide should be capable of inducing osteogenic differentiation of human adipose-derived stem cells when cultured on a three-dimensional polylactic-co-glycolic acid nano-fiber scaffold

Patient care application of results: Development of a stem-cell-enhanced allograft using an osteotropic peptide that has the potential to eliminate the need for autograft harvesting and its associated complications and morbidity

Simplified patient care application: Better fusions with fewer complications 

Turning Fat into Bone
OREF grant recipient investigates application of adipose stem cells to improve spinal-fusion outcomes
Mark Crawford

More than 350,000 spinal fusions are performed each year in the U.S. Despite significant technological improvements, up to 40% of these procedures result in pseudarthrosis, a condition that usually requires repeat surgery. Not only is this a major ordeal for patients, it’s a big concern for health-care systems that are desperate to control costs.

Bone autograft is the standard approach for spine fusion today; however, chances for developing complications are still high. Although allografts show promise, they still have serious drawbacks, such as poor osteoinductive properties and delayed onset of fusion.

With funding from  the Orthopaedic Research and Education Foundation (OREF), Brian C. Werner, MD, resident physician at the Department of Orthopaedic Surgery at University of Virginia in Charlottesville, plans to change that. He is using a $20,000 OREF Resident Clinician Scientist Training Grant to develop a unique allograft that he hopes will displace autografts as the preferred approach for spine fusion.  

Dr. Werner’s OREF research involves creating a bone allograft using stem cells from human adipose tissue, supported within a three-dimensional osteoconductive scaffold supplemented with an osteotropic peptide. 

“I was looking for novel ways to generate bone, and adipose stem cells have always interested me,” indicated Dr. Werner. “Most of our patients have some they can give us. People like the idea that their fat can be taken and turned into bone—it’s a cool translational idea. And it’s also very easy to talk to patients about it.”

A New Approach for Allografts
Dr. Werner designed and tested a bone-graft substitute by combining the osteogenic qualities of human adipose stem cells, a 3D polylactic-co-glycolic acid (PLGA) nanofiber scaffold, and R1 peptide. Osteotropic peptides provide key advantages over recombinant proteins such as BMP-2, including speed of preparation, molecular stability, long shelf life, and lower cost of manufacturing. Surprisingly, though, osteotropic peptides have not been previously investigated for use in spine fusion.

Two main research goals were established:

• Describe the osteogenic differentiation of human adipose-derived stem cells (hADSCs) cultured with an osteotropic peptide, loaded onto a three-dimensional PLGA nanofiber scaffold in vitro. Five experimental groups of hADSCs on nanofiber scaffolds were cultured in their respective mediums and growth factors for up to four weeks.  

• Evaluate the posterolateral fusion of the spine in rats by delivering hADSCs and osteogenic factor or peptide (GDF-5 or R1 peptide) on nanofiber scaffolds in vivo. Four experimental groups of rats were used, each receiving a different combination of scaffold, hADSCs, GDF-5, or R1 osteogenic peptide. Regenerative tissue was harvested at 4 weeks and 8 weeks.

Key to this research was the development of the PLGA nanofiber scaffold. In addition to being biocompatible and osteoconductive, it converts the tensile forces experienced in the posterolateral spine to compressive forces. When the nanofibers stretch, they effectively reduce the pore size, compressing the areas in which the cells reside. This helps keep the cells in place and enables them to attach and proliferate.

Promising Research
Results from other preliminary studies suggest that R1 osteotropic peptide should be capable of inducing osteogenic differentiation of human adipose-derived stem cells when cultured on a three-dimensional PLGA nano-fiber scaffold. If this holds true, then these cells should be capable of osteogenic differentiation and producing a posterolateral fusion of the spine in the rat model.

Dr. Werner is confident that his work will be a key step in the development of a stem cell-peptide-nanofiber allograft that can be used in any clinical setting where bone repair, healing, or fusion is necessary, especially spine, orthopedic trauma, hip, knee, foot, and ankle. 

“This kind of stem-cell-enhanced allograft using an osteotropic peptide has the potential to eliminate the need for autograft harvesting and its associated complications and morbidity, as well as reduce the cost associated with recombinant growth factors, ,” said Dr. Werner. “We believe this will result in more solid fusions by reducing the tension experienced by cells in a posterolateral spine.”

Dr. Werner is grateful for the research support from OREF. 

“For young clinician scientists like me who are just starting their careers in orthopaedic surgery, it is extremely important to be involved with OREF,” he said. “OREF supports a wide variety of orthopaedics and is very interested in orthopaedic education. They mentor young investigators by supporting us in residency, from small resident research project grants to the larger new investigator grants” 

Not only does an OREF grant provide critical funding for research, Dr. Werner indicated, applying for one helps researchers learn to organize their work, plan their research, and present information. “It has taught me a great deal about basic scientific approaches, especially how laboratories function,” he said. “This is information that will help me throughout my career.” 


General FAQs

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