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Layered gradient-pore plasma functionalized poly(ε-caprolactone) scaffolds promote uniform chondrocyte distribution and proliferation in 3D in vitro chondral models
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DOI：10.1016/j.reactfunctpolym.2026.106735.png)
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Abstract
En 中文
Three-dimensional scaffolds that recapitulate selected aspects of zonal cartilage architecture are increasingly used for in vitro chondral tissue modelling applications. We designed and fabricated four-layered gradient interconnected pore poly(epsilon-caprolactone) scaffolds with progressively decreasing pore sizes (from 112.1 +/- 28.0 mu m to 0.87 +/- 0.18 mu m) by combining melt-and solution electrospinning technologies. Three scaffold designs (S1-S3) were produced by varying the thicknesses of coarse-, medium-and fine-fibre layers (L1-L3) together with nanofibre layer (L4), while maintaining an overall thickness of the scaffold at similar to 640 mu m. Micro-CT confirmed an open and fully interconnected porous structure (porosity similar to 90%), while the specific surface area was highest for S3 and lowest for S1, which can be attributed to the thicker fine-fibre layer in S3. Surface properties were optimized by non-thermal plasma functionalization (0.39 J/cm(2)), which reduced the water contact angle from 108.0 +/- 1.7 degrees to 49.6 +/- 1.5 degrees and increased fibre roughness from 10.2 +/- 0.9 nm to 36.0 +/- 2.1 nm. Compression testing demonstrated morphology-dependent mechanical performance, with compressive modulus of 201.0 +/- 12.9 kPa (S1), 243.2 +/- 9.0 kPa (S2), and 301.6 +/- 15.5 kPa (S3), and comparable recovery under cyclic loading (similar to 83-84%). In vitro culture with C28/I2 human chondrocytes demonstrated that the scaffold design S3 supported the most uniform cell distribution and the highest proliferation over eight days, whereas S1-S2 exhibited cell crowding near the dense nanofibrous bottom layer, indicating insufficient scaffold architecture to support cell attachment in larger pores. These findings demonstrate that architecturally optimized, surface-activated gradient-pore poly(epsilon-caprolactone) scaffolds can serve as a versatile platform for engineering in vitro chondral tissue models with controllable, cartilage-relevant structural gradients.
Keywords:
Poly(epsilon-caprolactone)
Polymers
3D scaffolds
In vitro modelling
Gradient porosity
Chondral tissue
Electrospinning
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