In vitro studies on space-conforming self-assembling silk hydrogels as a mesenchymal stem cell-support matrix...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Neuroscience

Background:

• Advanced cell therapies necessitate reliable delivery systems.
• Silk-based materials offer a clinically validated option for therapeutic delivery.
• Mesenchymal stem cells (MSCs) are promising for neural repair but require suitable matrices.

Purpose of the Study:

• To optimize self-assembling silk hydrogels as a matrix for mesenchymal stem cells (MSCs).
• To enable future minimally invasive brain applications for cell therapy.
• To fine-tune silk hydrogel properties for enhanced cell support and delivery.

Main Methods:

• Utilized sonication energy to control silk secondary structure (random coil to β-sheet).
• Investigated silk concentrations (1-5% w/v) for hydrogel formation and properties.
• Assessed cell distribution, viability, and proliferation (in vitro) and space conformity (in vivo).

Main Results:

• Optimized silk hydrogels achieved space conformity without swelling, supporting uniform cell distribution and viability.
• Maximal MSC proliferation occurred in 2% w/v silk hydrogels over 14 days in vitro.
• Pre-gelled silk hydrogels enhanced MSC viability post-injection compared to post-gelled state.
• 4% w/v silk hydrogels demonstrated good space conformity in an in vivo ischemic brain cavity model.

Conclusions:

• Sonication-programmed silk hydrogels provide a tunable matrix for MSC delivery.
• Optimal hydrogel conditions were identified for MSC proliferation and viability, crucial for brain repair.
• These findings support the development of silk-hydrogel platforms for minimally invasive neural cell therapies.