Photo-induced in situ crosslinking of polymer brushes with dimethyl maleimide moieties for dynamically stimulating stem cell differentiation

Abstract

We designed photo-crosslinkable polymer brushes with dimethylmaleimide moieties, in order to demonstrate dynamic stimulation of cell differentiation in mesenchymal stem cells (MSCs). The polymer brushes were synthesized by surface-initiated reversible addition fragmentation chain transfer polymerization using dimethylmaleimide ethyl methacrylate and methyl methacrylate on a chain transfer agent-immobilized glass surface. The polymer brushes were crosslinked by photodimerization of the dimethylmaleimide moieties within polymer chains with stem cells present on the surface. In order to evaluate the effects of in situ photo-induced crosslinking of the polymer brushes on gene expression of stem cells, human bone marrow MSCs were cultured under static and dynamic culture conditions for 7 days. Expression of the osteocalcin (Ocn) gene in MSCs was used as an indicator of osteoblast differentiation under dynamic culture conditions. Structural conversion from non-crosslinked polymer brushes to crosslinked polymer brushes increased the expression of Ocn by 1.4-fold in the presence of adhered cells, compared with non-crosslinked polymer brushes under static culture conditions. These results suggest that MSCs recognized surface conversion from non-crosslinked to crosslinked structures, which resulted in altered differentiation lineages. Therefore, photo-crosslinkable surfaces with dimethyl maleimide moieties are potential novel materials for dynamically stimulating MSC differentiation.

Chemical and biological conjugation strategies for the development of multivalent protein vaccine nanoparticles

“…Maleimide conjugation has been utilized in protein nanoparticle vaccine formulations. [ 48,49 ] Jones et al [ 48 ] demonstrated a method to produce protein vaccine nanoparticles using malarial antigens via maleimide modification and thiolation. Pfs25M, AMA1, CSPM3 antigens from P. falciparum were conjugated separately using SATA (N-succinimidyl S-acetylthioacetate), which added sulfhydryl groups on each lysine via N-hydroxysuccinimide (NHS) ester conjugation.…”

Micropatterned Reactive Nanofibers: Facile Fabrication of a Versatile Biofunctionalizable Interface

“…While there are few examples of using cross-linker based strategies such as using photochemically induced radical thiol–ene reaction, , utilization of single-component photochemical cross-linking strategies for nanofibers is quite rare. Most reports of cross-linking of polymeric materials employ polymers bearing acrylate, methacrylate, and methacrylamide groups, cinnamates, benzophenones, uracil, and dimethylmaleimides. − While most reports utilize the dimethyl maleimide derivative, utilization of unsubstituted maleimide group provides avenue for post-cross-linking functionalization using the residual maleimide units. Recently, we reported that it is possible to fabricate cross-linked hydrogels from polymeric precursors containing maleimide groups .…”