Towards an in vitro model mimicking the foreign body response: tailoring the surface properties of biomaterials to modulate extracellular matrix

Despite various studies to minimize host reaction following a biomaterial implantation, an appealing strategy in regenerative medicine is to actively use such an immune response to trigger and control tissue regeneration. We have developed an in vitro model to modulate the host response by tuning biomaterials' surface properties through surface modifications techniques as a new strategy for tissue regeneration applications. Results showed tunable surface topography, roughness, wettability, and chemistry by varying treatment type and exposure, allowing for the first time to correlate the effect of these surface properties on cell attachment, morphology, strength and proliferation, as well as proinflammatory (IL-1β, IL-6) and antiflammatory cytokines (TGF-β1, IL-10) secreted in medium, and protein expression of collagen and elastin. Surface microstructuring, derived from chloroform partial etching, increased surface roughness and oxygen content. This resulted in enhanced cell adhesion, strength and proliferation as well as a balance of soluble factors for optimum collagen and elastin synthesis for tissue regeneration. By linking surface parameters to cell activity, we could determine the fate of the regenerated tissue to create successful soft tissue-engineered replacement

Enhancement of synthesis of extracellular matrix proteins on retinoic acid loaded electrospun scaffolds

Electrospinning is a renowned technique for the generation of ultrafine, micro- and nanoscale fibres due to its simplicity, versatility and tunability. Owing to its adaptability to a wide selection of materials and scaffold architectures, electrospun meshes have been developed as biocompatible scaffolds and drug delivery systems for tissue engineering. Here, we developed a drug delivery scaffold by electrospinning poly(ε-caprolactone) (PCL) directly blended with a therapeutic agent, retinoic acid (RA), at different concentrations. The release profile, DNA, and elastin analysis of direct and transwell seeded RA-loaded PCL electrospun scaffolds showed desirable controlled release at 15 kV fabrication, with 0.01% RA as the optimum concentration. The selected 0.01% (w/v) RA-loaded PCL meshes were further analysed using five different seeding cultures to investigate and extensively distinguish the effects of RA release with or without cell contact to the PCL electrospun meshes for cell morphology, proliferation and extracellular matrix (ECM) protein secretion of collagen and elastin. Upon exposure to RA-loaded PCL scaffolds, an increase of human dermal fibroblast (HDF) proliferation was observed. In contrast, human mesenchymal stromal cell (hMSC) cultures showed a decrease in cell proliferation. For both hMSC and HDF cultures, exposure to RA-loaded PCL scaffolds provided a significant increase in elastin production per cell. For collagen expression, a slight increase was measured and was outperformed by the 3D geometry stimulation from PCL scaffolds. In contrast to hMSCs, HDFs showed enhanced stress actin fibres in cultures with RA-loaded PCL scaffolds. Both cell types exhibited more vinculin expression when seeded to RA-loaded PCL scaffolds. Hence, electrospun scaffolds releasing RA in a controlled manner were able to regulate cell proliferation, morphology and ECM secretion, and present an attractive approach for optimizing tissue regeneration