The role of plasma‐induced surface chemistry on polycaprolactone nanofibers to direct chondrogenic differentiation of human mesenchymal stem cells

Abstract Bone marrow‐derived mesenchymal stromal cells (BMSCs) are extensively being utilized for cartilage regeneration owing to their excellent differentiation potential and availability. However, controlled differentiation of BMSCs towards cartilaginous phenotypes to heal full‐thickness cartilage defects remains challenging. This study investigates how different surface properties induced by either coating deposition or biomolecules immobilization onto nanofibers (NFs) could affect BMSCs chondro‐inductive behavior. Accordingly, electrospun poly(ε‐caprolactone) (PCL) NFs were exposed to two surface modification strategies based on medium‐pressure plasma technology. The first strategy is plasma polymerization, in which cyclopropylamine (CPA) or acrylic acid (AcAc) monomers were plasma polymerized to obtain amine‐ or carboxylic acid‐rich NFs, respectively. The second strategy uses a combination of CPA plasma polymerization and a post‐chemical technique to immobilize chondroitin sulfate (CS) onto the NFs. These modifications could affect surface roughness, hydrophilicity, and chemical composition while preserving the NFs' nano‐morphology. The results of long‐term BMSCs culture in both basic and chondrogenic media proved that the surface modifications modulated BMSCs chondrogenic differentiation. Indeed, the incorporation of polar groups by different modification strategies had a positive impact on the cell proliferation rate, production of the glycosaminoglycan matrix, and expression of extracellular matrix proteins (collagen I and collagen II). The chondro‐inductive behavior of the samples was highly dependent on the nature of the introduced polar functional groups. Among all samples, carboxylic acid‐rich NFs promoted chondrogenesis by higher expression of aggrecan, Sox9, and collagen II with downregulation of hypertrophic markers. Hence, this approach showed an intrinsic potential to have a non‐hypertrophic chondrogenic cell phenotype.