Investigating the microenvironmental effects of scaffold chemistry and topology in human mesenchymal stromal cell/polymeric hollow microfiber constructs

Tissue engineering scaffolds have shown an intrinsic ability to provide cellular stimulation, thus behaving as physically active microenvironments. This study reports on the interaction between human mesenchymal stromal cells (hMSCs) and dry-wet spun polymer microfiber meshes. The following scaffolding parameters were tested: i) polymer type: poly-L-lactide (PLLA) vs poly-ε-caprolactone (PCL); ii) non-solvent type: ethanol (Et-OH) vs isopropanol/ gelatin; iii) scaffold layout: patterned vs random microfiber fabrics. After two culture weeks, the effects on metabolic activity, scaffold colonization and function of undifferentiated hMSCs were assayed. In our study, the polymer type affected the hMSC metabolic activity timeline, and the metabolic picks occurred earlier in PLLA (day 6) than in PCL (day 9) scaffolds. Instead, PLLA vs PCL had no endpoint effect on alkaline phosphatase (ALP) activity expression. On average, the hMSCs grown on all the random microfiber fabrics showed an ALP activity statistically superior to that detected on patterned microfiber fabrics, with the highest in Et-OH random subtypes. Such findings are suggestive of enhanced osteogenic potential. The understanding of scaffold-driven stimulation could enable environmental hMSC commitment, paving the way for new regenerative strategies.