Poly(D,L-lactic acid)-Poly(ethylene glycol)-Monomethyl Ether Diblock Copolymers Control Adhesion and Osteoblastic Differentiation of Marrow Stromal Cells

Abstract

Biodegradable polymers, such as poly(lactic acid) (PLA) and poly(lactic-coglycolic acid) (PLGA), are attractive materials for tissue engineering because of their degradative and mechanical properties, which permit scaffolds to be tailored to the individual requirements of different tissues. Although these materials support tissue development, their chemical properties offer no control of cell adhesion or function because their surfaces become immediately masked by adsorbing serum proteins when the materials come into contact with body fluids. Furthermore, adhesion proteins undergo conformational changes and a decrease in bioactivity when adsorbed to hydrophobic materials, such as PLA. To overcome these limitations, we modified the properties of PLA by synthesizing a diblock copolymer with poly(ethylene glycol) (PEG), which is known to reduce the amount of adsorbed proteins and to modify their conformation. By altering the PEG content of these diblock copolymers we were able to control the adsorption of adhesion proteins and, because cell adhesion takes place only in the presence of serum proteins, to control cell adhesion and cell shape. Marrow stromal cell differentiation to the osteoblastic phenotype was strongly improved on PEG-PLA compared with PLA, PLGA and tissue culture polystyrene and led to a 2-fold increase in alkaline phosphatase activity and mineralization.

Preparation of poly(ethylene glycol)/polylactide hybrid fibrous scaffolds for bone tissue engineering

“…As reported, the blending of PEG to PLA can modulate the hydrophilicity property and significantly enhance osteoblastic differentiation. 33,34 Representative markers of the osteogenic procedure were comprehensively analyzed by mRNA quantitation and protein analysis (Figures 6-8). As the earliest osteogenic marker, mRNA level of Cbfa-1 was upregulated during the whole differentiation period and reached maximum expression on day 21.…”

“…32 Accordingly, electrospun hybrid scaffolds were prepared in this study by blending PLA with amphiphilic PEG as filler to tailor the scaffolds' hydrophilic properties, and to improve cell responses such as cell attachment, proliferation, and osteoblastic differentiation. 33,34 MSCs isolated from bone marrow are multipotent cells that can be induced to differentiate into a variety of mesenchymal tissues including bone, cartilage, tendon, fat, and muscle both in vitro and in vivo. 1 MSCs have been widely applied in tissue engineering because they are easy to get and manipulate, can be easily differentiated, are biocompatible almost without immune response or tumorigenesis, and especially because they pose no ethical or legal problems.…”

Customized PEG‐Derived Copolymers for Tissue‐Engineering Applications

“…Two-dimensional experiments with the same polymers on casted films also provided evidence that these polymers [76] can be used to covalently bind peptide sequences to achieve selective cell adhesion mediated by cyclic RGD sequences. Here, the sequences were also bound using the instant chemistry with amine or sulfhydryl groups.…”

“…[75] Additional investigations of the obtained polymer films using cells revealed the suppression effect of the hydrophilic polymers on the adhesion and consequent proliferation of cells, which can also be used for the prevention of adhesion after surgical procedures. [76,77] It could be demonstrated that, depending on the PEG content, cell adhesion could be varied from the formation of small cell aggregates or no cells to cell spreading comparable with the standard cell culture polymers, poly(lactic acid) or tissue culture polystyrene ( Figure 13). Moreover, it was shown that upon irradiation with UV light, the adhesion-suppressing properties are lost and complete removal of the PEG chains on the surface could be achieved due to cleavage of the bonds exposed to UV light on the surface of the films.…”

Structural and functional characterization of proteins adsorbed on hydrophilized polylactide-co-glycolide microfibers

“…However, the higher lactic acid content leads to an increase in the hydrophobicity of the PLGA system, which in turn can adversely influence protein interaction and subsequent cellular behavior. [9][10][11][12][13] Exposure of such an extracellular matrix mimicking fibrous scaffold to the biological environment at the site of implantation would normally result in rapid adsorption of proteins onto the surface of the scaffold. The amount, orientation, and conformation of the adsorbed proteins is largely regulated by the surface properties of the scaffold, including surface chemistry, roughness, and charge.…”