a microscopic photo of stem cells

Engineering researchers develop porous nanoparticles for regenerative medicine

Akhilesh K. Gaharwar is leading research to develop a new class of porous nanoparticles capable of directing stem cell differentiation. In the photo above, the purple sections are the actin cytoskeleton of human mesenchymal stem cells, the blue dot in the upper left area is the cell nucleus, and the green represents the 2D Covalent Organic Framework (COF) nanoparticles.

Courtesy of Akhilesh K. Gaharwar

Stem cells can develop into many different types of cells in the body. For example, when a person is injured, stem cells arrive at the injury site and help heal the damaged tissue. New nanotechnology developed by a team of Texas A&M University researchers could harness the body’s regenerative potential by directing stem cells to form bone.

Akhilesh K. Gaharwar, associate professor and Presidential Impact Fellow in the Department of Biomedical Engineering and a member of the American Institute for Medical and Biological Engineering, leads the team. Researchers developed covalent organic framework (COF) water-stable 2D nanoparticles that can direct the differentiation of human mesenchymal stem cells into bone cells.

Significant research attention has been given to 2D COFs – porous organic polymers – due to their crystallinity, ordered and adjustable porous structure and high specific surface area. However, the difficulty of transforming COFs into nano-sized materials, coupled with their poor stability, has limited their application in regenerative medicine and drug delivery. Novel approaches are needed that provide these COFs with sufficient physiological stability while maintaining their biocompatibility.

Gaharwar’s team improved the hydrolytic (water) stability of COFs by supplementing them with amphiphilic polymers, which are macromolecules that contain both hydrophobic and hydrophilic components. This approach, which has not been previously reported, gives COFs dispersibility in water, enabling the biomedical application of these nanoparticles.

“As far as we know, this is the first report that demonstrates the ability of COFs to direct stem cells to bone,” said Gaharwar. “This new technology has the potential to impact the treatment of bone regeneration.”

The researchers found that 2D COFs do not affect a cell’s viability and proliferation, even at higher concentrations. They observed that these 2D COFs exhibit bioactivity and direct stem cells to bone cells. The preliminary study indicated that the shape and size of these nanoparticles may confer this bioactivity and that further in-depth studies are needed for mechanistic insights.

These nanoparticles are highly porous, and Gaharwar’s team exploited this unique feature for drug delivery. They were able to load an osteoinductive drug called dexamethasone into the porous structure of the COF to further improve bone formation.

“These nanoparticles could prolong drug delivery to human mesenchymal stem cells, which are commonly used in bone regeneration,” said Sukanya Bhunia, senior author of the study and postdoctoral associate in the biomedical engineering department. “Prolonged administration of the drug has led to greater differentiation of stem cells towards the bone lineage and this technique can be used for bone regeneration.”

Gaharwar noted that after providing a proof of concept, the team’s next step in their research will be to evaluate this nanotechnology in a diseased model.

These findings are important for the future design of biomaterials capable of providing guidance for tissue regeneration and drug delivery applications.

The results were published in Advanced sanitary materials magazine. Other contributors to the research are Manish Jaiswal, Kanwar Abhay Singh, and Kaivalya Deo of the Texas A&M Department of Biomedical Engineering. The research was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health.

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