Duke University researchers say they have moved a step closer to being able to generate replacement cartilage where it’s needed in the body by combining a synthetic scaffolding material with gene delivery methods.
Initiating tissue repair with stem cells usually requires the use of large amounts of growth factors. Experience has demonstrated that this is expensive and can be challenging once the developing material is implanted within a body.
In a new study (“Scaffold-mediated lentiviral transduction for functional tissue engineering of cartilage”) in PNAS, the Duke team found a way around this limitation by genetically altering the stem cells to make the necessary growth factors all on their own.
They incorporated viruses used to deliver gene therapy to the stem cells into a synthetic material that serves as a template for tissue growth. The resulting material is like a computer; the scaffold provides the hardware and the virus provides the software that programs the stem cells to produce the desired tissue.
Farshid Guilak, Ph.D., director of orthopedic research at Duke University Medical Center, notes that one challenge he and all biomedical researchers face is getting stem cells to form cartilage within and around the scaffolding, especially after it is implanted into a living being. The traditional approach has been to introduce growth factor proteins, which signal the stem cells to differentiate into cartilage. Once the process is under way, the growing cartilage can be implanted where needed.
“But a major limitation in engineering tissue replacements has been the difficulty in delivering growth factors to the stem cells once they are implanted in the body,” explains Dr. Guilak, who is also a professor in Duke’s department of biomedical engineering. So they developed a new approach.
“The goal of this study was to generate a self-contained bioactive scaffold capable of mediating stem cell differentiation and formation of a cartilaginous extracellular matrix (ECM) using a lentivirus-based method,” write the investigators. “We first showed that poly-L-lysine could immobilize lentivirus to poly(ε-caprolactone) films and facilitate human mesenchymal stem cell (hMSC) transduction. We then demonstrated that scaffold-mediated gene delivery of transforming growth factor β3 (TGF-β3), using a 3D woven poly(ε-caprolactone) scaffold, induced robust cartilaginous ECM formation by hMSCs.”
While this study focuses on cartilage regeneration, the Duke researchers believe the technique could be applied to many kinds of tissues, especially orthopedic tissues such as tendons, ligaments, and bones. And because the platform comes ready to use with any stem cell, it presents an important step toward commercialization.
“One of the advantages of our method is getting rid of the growth factor delivery, which is expensive and unstable, and replacing it with scaffolding functionalized with the viral gene carrier,” points out Charles Gersbach, Ph.D., an assistant professor of biomedical engineering and an expert in gene therapy. “The virus-laden scaffolding could be mass-produced and just sitting in a clinic ready to go. We hope this gets us one step closer to a translatable product.”