The effects of poly(dimethylsiloxane) surface silanization on the mesenchymal stem cell fate

Abstract

In recent years, poly(dimethylsiloxane) (PDMS)-based microfluidic devices have become very popular for on-chip cell investigation. Maintenance of mammalian cell adhesion on the substrate surface is crucial in determining the cell viability, proliferation and differentiation. However, the inherent hydrophobicity of PDMS is unfavourable for cell culture, causing cells to eventually dislodge from the surface. Although physically adsorbed matrix proteins can promote initial cell adhesion, this effect is usually short-lived. To address this critical issue, in this study, we employed (3-aminopropyl) triethoxy silane (APTES) and cross-linker glutaraldehyde (GA) chemistry to immobilize collagen type 1 (Col1) on PDMS. These modified surfaces are highly efficient to support the adhesion of mesenchymal stem cells (MSCs) with no deterioration of their potency. Significant changes of the native PDMS surface properties were observed with the proposed surface functionalization, and MSC adhesion was improved on PDMS surfaces modified with APTES + GA + Protein. Therefore, this covalent surface modification could generate a more biocompatible platform for stabilized cell adhesion. Furthermore, this modification method facilitated long-term cell attachment, which is favourable for successful induction of osteogenesis and cell sheet formation with an increased expression of osteogenic biomarkers and comparable extracellular matrix (ECM) constituent biomarkers, respectively. The surface silanization can be applied to PDMS-based microfluidic systems for long-term study of cellular development. Similar strategies could also be applied to several other substrate materials by appropriate combinations of self-assembled monolayers (SAMs) and ECM proteins.

Recent advances in nonbiofouling PDMS surface modification strategies applicable to microfluidic technology

“…These values remained stable for approximately 30 days. Recently, Chuah et al silanized PDMS surfaces with (3-aminopropyl)triethoxy silane (APTES) and used glutaraldehyde (GA) crosslinking to modified the surface properties of PDMS, including reduction of hydrophobicity, increased protein immobilization, and variation of nanotopography 38 . The route followed for the PDMS surface modification is shown in Fig.…”

“…Although PDMS has many merits, its high hydrophobicity (water contact angle ~108° ± 7°) 36–38 often limits its applications where solutions containing biological samples are concerned. A major consequence of this hydrophobicity is undesired nonspecific adsorption of proteins which influences analyte transportation, and thus reduced separation performance and detection sensitivity 39 .…”

An oxygen plasma treated poly(dimethylsiloxane) bioscaffold coated with polydopamine for stem cell therapy

“…Indeed, this has been identified as the primary factor for poor cell adhesion on PDMS bioscaffolds with the creation of dissociating islands of cell aggregates. In turn, this renders the surface of PDMS incompatible for cell adhesion and proliferation [14–16]. …”

“…For example, one strategy is to coat the surface with extracellular matrix proteins, which has been shown to improve cell adhesion and proliferation. However, cell detachment is typically seen following prolonged culture due to protein dissociation [16, 19]. To overcome this problem, studies have chemically modified the surface of PDMS with (3-aminopropyl)triethoxy silane (APTES) and then used glutaraldehyde to cross-link a protein coating onto the surface of PDMS.…”

“…To overcome this problem, studies have chemically modified the surface of PDMS with (3-aminopropyl)triethoxy silane (APTES) and then used glutaraldehyde to cross-link a protein coating onto the surface of PDMS. Although this surface treatment approach is very effective with improved cell adhesion and proliferation [16, 17], the process is time-consuming with numerous intermediate steps. Moreover, the use of toxic chemicals, such as APTES and glutaraldehyde, poses potential health hazards and creates chemical wastes which are toxic to the environment.…”