Electrochemical quartz crystal microbalance with dissipation investigation of fibronectin adsorption dynamics driven by electrical stimulation onto a conducting and partially biodegradable copolymer.

Functional surface coatings are a key option for biomedical applications, from polymeric supports for tissue engineering to smart matrices for controlled drug delivery. Therefore, the synthesis of new materials for biological applications and developments is promising. Hence, biocompatible and stimuli-responsive polymers are interesting materials, especially when they present conductive properties. PEDOT-co-PDLLA graft copolymer exhibits physicochemical and mechanical characteristics required for biomedical purposes, associated with electroactive, biocompatible, and partially biodegradable properties. Herein, the study of fibronectin (FN) adsorption onto PEDOT-co-PDLLA carried out by an electrochemical quartz crystal microbalance with dissipation is reported. The amount of FN adsorbed onto PEDOT-co-PDLLA was higher than that adsorbed onto the Au surface, with a significant increase when electrical stimulation was applied (either at +0.5 or -0.125 V). Additionally, FN binds to the copolymer interface in an unfolded conformation, which can promote better NIH-3T3 fibroblast cell adhesion and later cell development.

The effect of nanoscale surface electrical properties of partially biodegradable PEDOT-co-PDLLA conducting polymers on protein adhesion investigated by atomic force microscopy.

This study used atomic force microscopy (AFM) to elucidate the interaction of fibronectin (FN) on a conducting and partially biodegradable copolymer of poly(3,4-ethylenedioxythiophene) and poly(d,l-lactic acid) (PEDOT-co-PDLLA) in three different proportions (1:05, 1:25 and 1:50). The copolymers with higher PEDOT:PDLLA content ratios (1:05 and 1:25) had higher surface roughness, water contact angle, with current and conductivity occurring at discrete large grain structures on the surface. In contrast, the lower PEDOT:PDLLA content ratio (1:50) did not show high conductivity grains but showed homogenous surface conductivity across the entire surface. Using FN-functionalized AFM probes, force measurements showed that the copolymers with higher PEDOT content (1:05 and 1:25) had significantly lower adhesion forces (~0.2-0.3 nN), while the copolymer with the lower content of PEDOT (1:50) had stronger FN interactions with significantly higher adhesion forces of 1 nN. By correlating the spatially distributed electrical surfaces with FN interactions, we observed that the synthesis of 1:50 PEDOT:PDLLA produced more uniformly doped polymer films that facilitated FN adsorption through favorable interactions with accessible sulfate dopants. Importantly, these findings are correlated with previous studies showing increased stem cell migration and differentiation on 1:50 PEDOT:PDLLA surfaces compared with surfaces with 1:05 and 1:25 PEDOT:PDLLA ratios.

Novel Conducting and Biodegradable Copolymers with Noncytotoxic Properties toward Embryonic Stem Cells.

Electroactive biomaterials that are easily processed as scaffolds with good biocompatibility for tissue regeneration are difficult to design. Herein, the synthesis and characterization of a variety of novel electroactive, biodegradable biomaterials based on poly(3,4-ethylenedioxythiphene) copolymerized with poly(d,l lactic acid) (PEDOT-co-PDLLA) are presented. These copolymers were obtained using (2,3-dihydrothieno[3,4-b][1,4]dioxin-2-yl)methanol (EDOT-OH) as an initiator in a lactide ring-opening polymerization reaction, resulting in EDOT-PDLLA macromonomer. Conducting PEDOT-co-PDLLA copolymers (in three different proportions) were achieved by chemical copolymerization with 3,4-ethylenedioxythiophene (EDOT) monomers and persulfate oxidant. The PEDOT-co-PDLLA copolymers were structurally characterized by 1H NMR and Fourier transform infrared spectroscopy. Cyclic voltammetry confirmed the electroactive character of the materials, and conductivity measurements were performed via electrochemical impedance spectroscopy. In vitro biodegradability was evaluated using proteinase K over 35 days, showing 29-46% (w/w) biodegradation. Noncytotoxicity was assessed by adhesion, migration, and proliferation assays using embryonic stem cells (E14.tg2a); excellent neuronal differentiation was observed. These novel electroactive and biodegradable PEDOT-co-PDLLA copolymers present surface chemistry and charge density properties that make them potentially useful as scaffold materials in different fields of applications, especially for neuronal tissue engineering.

One pot biocatalytic synthesis of a biodegradable electroactive macromonomer based on 3,4-ethylenedioxytiophene and poly(l-lactic acid).

A novel electroactive macromonomer based on poly(l-lactic acid) (PLLA) with (3,4-ethylenedioxythiophene) (EDOT) functional end groups, was prepared by a traditional approach of organometallic polymerization with stannous octanoate [Sn(oct2)] and enzymatic polymerization using immobilized Candida antarctica Lipase B (CAL-B) and Amano lipase Pseudomonas cepacia(PS-IM), as catalysts. In the synthetic strategy, (2,3-dihydrothieno[3,4-b] dioxin-2-yl)methanol (EDOT-OH) was used to initiate the ring opening polymerization of lactide to yield PLLA with EDOT end group. All macromonomers (EDOT-PLLA) were characterized by 1H and 13C RMN, MALDI-TOF, GPC and EDX. Moreover, ICP-OES analysis showed the presence of Sn traces in the material synthesized by the traditional approach, but that pathway led to macromonomers with higher molecular weight while the enzymatic route led to completely metal-free macromonomers with medium and lower molecular weights. Also, electrochemical and chemical polymerization of EDOT-PLLA were tested showing that it is possible to prepare degradable conducting polymers based on poly(3,4-ethylenedioxythiphene) (PEDOT). The biocatalytic synthesis is a very promising and environmental friendly pathway for the preparation of biodegradable materials for short time applications.