In the recently published ‘A Drug-Eluting 3D-Printed Mesh (GlioMesh) for Management of Glioblastoma,’ Canadian researchers take on the topic of using 3D printing for better treatment of glioblastoma (GBM) as current surgical procedures, radiation therapy, and medications still do not seem to be making an impact on survival rates.
In this study, the researchers offer a new method for treatment, via GlioMesh, made from 3D printed hydrogels that are filled with temozolomide microparticles (TMZ). GBMs are one of the most aggressive forms of brain cancer, affecting nearly 50 percent of patients with brain tumors within the US. Today, there is less than a ten percent chance of survival over five years for patients diagnosed with GBM.
“The standard therapy for GBM is maximal safe surgical resection, followed by radiation and chemotherapy with temozolomide (TMZ) for 6 months,” explain the researchers. “After the radiotherapy is finished, the monthly administration of TMZ is maintained for 6 months up to one year. Together, these typically add only months of additional survival. Even with the current advances in microsurgical techniques, tumor recurrence is the norm, typically occurring within 1–2 cm of the original tumor border.”
Obstacles in treating/managing GBM include:
- Issues with complete removal of the tumor, often spread in ‘finger-like projections’
- Ineffectiveness of chemotherapy to treat areas deep within brain tissue
- Challenges due to the blood-brain/tumor barrier
- Drug-resistant characteristics of GBM cancer stem cells
The researchers are striving to:
- Increase the amount of survival time
- Increase long-term survival rate
- Improve quality of life for patients
While TMZ can overcome the blood-brain barrier, high doses are often required, and side effects can be brutal; however, the researchers explain that is it possible to bypass some of these challenges with localized delivery of the drug. With the drug-releasing mesh developed for this study (consisting of alginate hydrogel and laden with TMZ‐loaded PLGA microspheres), the researchers found they could release TMZ over the tumor site for seven weeks at a time.
“Fabrication of a porous mesh by 3D printing is an enabling technology that offers the advantages of higher mass transport of the drug to the surrounding tissue due to higher surface to volume ratios, better cellular infiltration, and enhanced delivery of nutrients and oxygen to the underlying tissue,” explained the researchers.
The study showed poor ‘encapsulation efficiencies’ of 0.87 ± 0.52%, and 1.34 ± 0.03% for the microspheres prepared with O/W and W/O/W emulsion, respectively. This had also been the result for previous researchers engaging in similar work. Further refinements did not show much of an improvement.
As the researchers increased print-head pressure, they were finally able to deposit more alginate, increasing fiber diameter. Greater control over the 3D printed meshes occurred with the proper amount of viscosity. Adding polymeric microspheres also helped encourage longer TMZ release at the tumor.
“GlioMesh demonstrated a sustained release of TMZ over 56 days, which circumvents the need for frequent oral administration of this chemotherapy drug in GBM patients,” concluded the researchers. “GlioMesh showed superior cytotoxic effect over free TMZ due to the preservation of the drug from degradation over the course of treatment and maintaining the level of autophagy in GBM cells.
“Furthermore, higher degree of mitochondrial damage was achieved by sustained delivery of TMZ in comparison with free TMZ. All in all, GlioMesh holds great promise in the management of GBM by reducing the side effects of chemotherapy, circumventing the BBB and associated challenges, and providing more flexibility toward using a combinational therapy approach that is tailored to each patient.”
The amount of cancer research and treatment today that includes 3D printing in its successes is staggering—from microfluidic devices to the printing of tumors, microtumors, and more for assistance in critical research.
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[Source / Images: ‘A Drug-Eluting 3D-Printed Mesh (GlioMesh) for Management of Glioblastoma’]
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