Sulfated Hyaluronan Containing Collagen Matrices Enhance Cell-Matrix-Interaction, Endocytosis, and Osteogenic Differentiation of Human Mesenchymal Stromal Cells

Inorganic–organic composite implant materials
mimicking
the environment of bone are promising applications to meet the increasing
demands on biomaterials for bone regeneration caused by extended life
spans and the concomitant increase of bone treatments. Besides collagen
type I (Col-I) glycosaminoglycans (GAG), such as hyaluronan, are important
components of the bone extracellular matrix (ECM). Sulfated GAGs are
potential stimulators of bone anabolic activity, as they are involved
in the recruitment of mesenchymal stromal cells (MSCs) to the site
of bone formation and support differentiation to osteoblasts. Nevertheless,
no consecutive data is currently available about the interaction of
hyaluronan or sulfated hyaluronan derivatives with hMSCs and the molecular
processes being consequently regulated. We applied quantitative proteomics
to investigate the influence of artificial ECM composed of Col-I and
hyaluronan (Hya) or sulfated hyaluronan (HyaS3) on the molecular adaptation
of osteogenic-differentiated human MSCs (hMSCs). Of the 1,370 quantified
proteins, the expression of 4–11% was altered due to both aECM-combinations.
Our results indicate that HyaS3 enhanced multiple cell functions,
including cell-matrix-interaction, cell-signaling, endocytosis, and
differentiation. In conclusion, this study provides fundamental insights
into regulative cellular responses associated with HyaS3 and Hya as
components of aECM and underlines the potential of HyaS3 as a promising
implant-coating-material.