Polylactide/Polycaprolactone Nanofiber Scaffold Enhances Primary Cortical Neuron Growth

Area of Science:

• Biomaterials Science
• Neuroscience
• Tissue Engineering

Background:

• Spinal cord injury (SCI) presents significant challenges due to the limited regeneration of the central nervous system (CNS).
• Effective tissue engineering scaffolds require mechanical compatibility, controlled degradation, and microarchitectural features that support neuronal survival and integration.
• Electrospun nanofibrous scaffolds offer a promising approach by mimicking the extracellular matrix and providing cues for neural regeneration.

Purpose of the Study:

• To fabricate and characterize biodegradable poly(lactic acid)/poly(ε-caprolactone) (PLA/PCL) scaffolds using a specific solvent system for enhanced neural tissue repair.
• To investigate the impact of scaffold microarchitecture, controlled by solvent choice, on neuronal survival and glial cell morphology in vitro.
• To evaluate the potential of these scaffolds as a platform for central nervous system (CNS) tissue engineering.

Main Methods:

• Fabrication of PLA/PCL nanofibrous scaffolds using a dichloromethane/tetrahydrofuran (DCM/THF) solvent system to induce surface porosity.
• Characterization of scaffold mechanical properties (Young's modulus) and degradation behavior under simulated post-injury oxidative conditions.
• In vitro assessment of neuronal density, viability, and glial cell morphology in primary neuron-glia cultures seeded on scaffolds fabricated with DCM/THF versus hexafluoroisopropanol (HFIP).

Main Results:

• The DCM/THF solvent system produced PLA/PCL nanofibers with porous surfaces, increasing cell interaction area and a Young's modulus of approximately 26 MPa.
• Scaffolds exhibited sustained degradation, particularly under oxidative conditions relevant to the SCI microenvironment.
• In vitro studies showed a fivefold increase in neuronal density and maintained neuronal viability (~80% over 10 days) on DCM/THF scaffolds.
• DCM/THF scaffolds supported astrocytes with preserved process complexity and reduced circularity, indicating a less reactive morphology compared to HFIP-fabricated scaffolds.

Conclusions:

• Solvent-driven control over scaffold microarchitecture is a critical factor in enhancing neuronal integration and modulating glial responses.
• PLA/PCL scaffolds fabricated using the DCM/THF solvent system demonstrate superior bioactivity and promote a favorable cellular environment for neural regeneration.
• These DCM/THF-processed PLA/PCL scaffolds represent a promising biomaterial platform for CNS tissue engineering applications aimed at treating spinal cord injury.