Thin Polymer Brush Decouples Biomaterial's Micro-/Nano-Topology and Stem Cell Adhesion

Surface morphology and chemistry of polymers used as biomaterials, such as tissue engineering scaffolds, have a strong influence on the adhesion and behavior of human mesenchymal stem cells. Here we studied semicrystalline poly(ε-caprolactone) (PCL) substrate scaffolds, which exhibited a variation of surface morphologies and roughness originating from different spherulitic superstructures. Different substrates were obtained by varying the parameters of the thermal processing, i.e. crystallization conditions. The cells attached to these polymer substrates adopted different morphologies responding to variations in spherulite density and size. In order to decouple substrate topology effects on the cells, sub-100 nm bio-adhesive polymer brush coatings of oligo(ethylene glycol) methacrylates were grafted from PCL and functionalized with fibronectin. On surfaces featuring different surface textures, dense and sub-100 nm thick brush coatings determined the response of cells, irrespective to the underlying topology. Thus, polymer brushes decouple substrate micro-/nano-topology and the adhesion of stem cells

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Covalent surface immobilization of Arg-Gly-Asp- and Tyr-Ile-Gly-Ser-Arg-containing peptides to obtain well-defined cell-adhesive substrates

The synthetic peptides Gly-Arg-Gly-Asp-Tyr and Gly-Tyr-Ile-Gly-Ser-Arg-Tyr, which contain Arg-Gly-Asp (RGD) and Tyr-Ile-Gly-Ser-Arg (YIGSR), the ligands for two important classes of cell adhesion receptors, were covalently coupled to a nonadhesive modified glass surface by the N-terminal Gly. The N-terminal Gly served as a spacer, and the C-terminal Y served as a site for radioiodination. These modified substrates supported the adhesion and spreading of cultured human foreskin fibroblasts (HFFs) independently of adsorbed proteins and, it was demonstrated that a covalently immobilized YIGSR-containing peptide has biological activity. The surface concentration of grafted peptide on the glass was measured by 125I radio-labeling and was 12.1 pmol/cm2. HFFs spread on both immobilized peptide substrates, but at much slower rates on grafted YIGSR glass surfaces than on the RGD-containing substrates. Cells formed focal contacts on the RGD-derivatized substrates in the presence or absence of serum. Focal contacts formed on the YIGSR-grafted surfaces only when serum was present in the medium and had morphologies different from those observed on the RGD-containing substrates. Serum influenced the organization of microfilaments and the extent of spreading of adherent cells, although adsorption of adhesion proteins was minimal on all substrates. This derivatization method produced chemically stable substrates which may be useful in studying receptor-mediated cell adhesion, as the quantity of peptide available at the surface may be precisely measured and controlled. [on SciFinder (R)

Human endothelial cell interactions with surface-coupled adhesion peptides on a nonadhesive glass substrate and two polymeric biomaterials

The attachment, spreading, spreading rate, focal contact formation, and cytoskeletal organization of human umbilical vein endothelial cells (HUVECs) were investigated on substrates that had been covalently grafted with the cell adhesion peptides Arg-Gly-Asp (RGD) and Tyr-Ile-Gly-Ser-Arg (YIGSR). This approach was used to provide substrates that were adhesive to cells even in the absence of serum proteins and with no prior pretreatment of the surface with proteins of the cell adhesion mol. (CAM) family. This approach was used to enhance the cell-adhesiveness of substrates that were otherwise cell-nonadhesive and to improve control of cellular interactions with cell-adhesive materials by providing stably bound adhesion ligands. Glycophase glass was examd. as a model cell-nonadhesive substrate prior to modification, and polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) were examd. as representative materials for biomedical applications. The peptides were surface-coupled by their N-terminal amine to surface hydroxyl moieties using tresyl chloride chem. Prior to peptide grafting, the PET and PTFE were surface hydroxylated to yield PET-OH and PTFE-OH. The PET-OH was less cell-adhesive and the PTFE-OH was much more cell-adhesive than the native polymers. Radioiodination of the C-terminal tyrosine residue was used to quantify the amt. of peptide coupled to the surface, and these amts. were 12.1 pmol/cm2 on glycophase glass, 139 fmol/cm2 on PET-OH, and 31 fmol/cm2 on PTFE-OH. Although the glycophase glass did not support adhesion or spreading even in the presence of serum, the RGD- and YIGSR-grafted glycophase glass did support adhesion and spreading, even when the only serum protein that was included was albumin. Although PET and PTFE-OH supported adhesion when incubated in serum-supplemented medium, neither of these materials supported adhesion with only albumin present, indicating that cell adhesion is mediated by adsorbed CAM proteins. When these materials were peptide-grafted, however, extensive adhesion and spreading did occur even when only albumin was present. Since the peptide grafting is quite easily controlled and is temporally stable, while protein adsorption is quite difficult to precisely control and is temporally dynamic, peptide grafting may be advantageous over other approaches employed to improve long-term cell adhesion to biomaterials. [on SciFinder (R)