Long-term release of regulatory genes to repair femoral head
Long-term release of regulatory genes to repair femoral head lead image
Prolonged alcohol abuse can impair the function of bone marrow stem cells in the femoral head, forming necrotic areas. While alcohol-induced osteonecrosis of the femoral head (ONFH) often requires hip replacement surgery, injectable gene therapy is a minimally invasive—but temporary—alternative.
Alcohol-induced ONFH requires long-term, continuous treatment. However, frequent injections in the femoral head pose a medical risk. Fu et al. developed heat-sensitive nanocomposite hydrogels that deliver long-lasting gene therapy with a single injection.
At room temperature, the hydrogel is a liquid and can be injected into the femoral head. After injection, body heat solidifies the hydrogel. As the solidified hydrogel stays in the body, it continuously releases regulatory genes.
These genes, in the form of circular RNA and small interfering RNA, regulate gene expression in bone marrow stem cells to restore function. Specifically, they increase the production of the protein B-cell lymphoma 2 to inhibit stem cell death and decrease the production of the protein PPARγ to inhibit adipogenic differentiation of stem cells. This reverses abnormal activity and allows the bone marrow stem cells to repair necrotic areas.
The authors found one injection of the hydrogel reduced osteonecrosis in rats for one month. Next, they plan to help translate this treatment to patients in a clinical setting.
“The nanocomposite hydrogels we designed have excellent clinical applications,” said author Feng Lin. “It is hoped that our biomaterials can enter the clinic as soon as possible and bring good news to more patients with ONFH.”
The injectable nanocomposite hydrogel system may also be useful for delivering gene therapies to treat other chronic diseases.
Source: “Injectable heat-sensitive nanocomposite hydrogel for regulating gene expression in the treatment of alcohol-induced osteonecrosis of the femoral head,” by Zherui Fu, Yi Lai, Yaping Zhuang, and Feng Lin, APL Bioengineering (2023). The article can be accessed at https://doi.org/10.1063/5.0130711 .
