- Open Access
Immobilization of Gelatin onto Poly(Glycidyl Methacrylate)-Grafted Polycaprolactone Substrates for Improved Cell–Material Interactions
© The Author(s) 2012
Received: 10 February 2012
Accepted: 5 April 2012
Published: 24 April 2012
To enhance the cytocompatibility of polycaprolactone (PCL), cell-adhesive gelatin is covalently immobilized onto the PCL film surface via two surface-modified approaches: a conventional chemical immobilization process and a surface-initiated atom transfer radical polymerization (ATRP) process. Kinetics studies reveal that the polymer chain growth from the PCL film using the ATRP process is formed in a controlled manner, and that the amount of immobilized gelatin increases with an increasing concentration of epoxide groups on the grafted P(GMA) brushes. In vitro cell adhesion and proliferation studies demonstrate that cell affinity and growth are significantly improved by the immobilization of gelatin on PCL film surfaces, and that this improvement is positively correlated to the amount of covalently immobilized gelatin. With the versatility of the ATRP process and tunable grafting efficacy of gelatin, this study offers a suitable methodology for the functionalization of biodegradable polyesters scaffolds to improve cell–material interactions.
Due to its slow degradation rate in vivo, good processability, and appropriate mechanical properties, polycaprolactone (PCL) is currently being extensively investigated as a scaffold material for tissue engineering applications [1–8]. However, the intrinsic hydrophobicity of PCL substrates results in poor cell attachment properties, thereby restricting their applications as biomaterials [8–17]. Modification of PCL substrate surfaces with physiological or biological activities has proven to be an effective strategy to promote cell adhesion and growth. Various methods, such as hydrolysis [13, 18, 19], aminolysis [5, 10, 20–23], plasma treatment [8, 11–16, 24, 25], UV-induced copolymerization [9, 26], ion-beam irradiation , and ozone treatment , have been employed in immobilizing extracellular matrix (ECM) molecules (e.g., collagen, gelatin and chitosan) and small active peptide sequences (e.g. Arg-Gly-Asp (RGD)) onto the PCL substrates to induce cell-specific interactions. Alternatively, functional polymer brushes containing reactive hydroxyl, carboxyl or amine groups have been grafted onto the PCL surfaces using γ-ray irradiated, ozone or photo-induced grafting to introduce hydrophilicity [14, 29–31]. These flexible reactive groups on the polymer brushes are well-suited to conjugate bioactive macromolecules for improved cytocompatibility. However, γ-ray irradiated, ozone or photo-induced polymerization grafting of polymer brushes has several limitations, including low density of grafting due to steric hindrance, uncontrollable graft yield of polymer brushes, and undesired formation of a covalent bond between reactive groups on the polymer brushes and the surface . Hence, alternative methods that allow control over brush density, polydispersity and composition are desired.
One such alternative is the use of surface-initiated atom transfer radical polymerization (ATRP) method to covalently attach polymer brushes in a tunable and controllable manner [33–35]. This approach allows the preparation of polymer brushes bearing reactive pendant groups, such as hydroxyl, carboxylic acid, or epoxide groups, which provide highly reactive binding sites for bioactive macromolecules at the brush interfaces . Hence, surface-initiated ATRP is a promising approach for the functionalization of the PCL surface, as it allows for the control of the length and density of the polymer brushes, which leads to tunable grafting efficiency for the desired biologically active molecules. However, to the best of our knowledge, few studies have been devoted to modifying biodegradable polyester polymers using surface-initiated ATRP for the improvement of their cytocompatibility . Moreover, no systematic study has been performed to investigate the relationship between the surface density of the grafted bioactive molecules and cellular functions in order to demonstrate the tunable grafting efficiency of this approach.
Polycaprolactone pellets (PCL, average M n 45,000), 1,6-hexanediamine (98 %), glycidyl methacrylate (GMA, >97 %), 2-bromoisobutyrl bromide (BIBB, 98 %), 2,2′-bipyridine (Bpy, 98 %), dichloromethane (anhydrous, >99.8 %), triethylamine (TEA, 98 %), isopropyl alcohol, hexane (anhydrous, >95 %), glutaraldehyde (25 %, Grade I), ninhydrin (>95 %), copper (I) bromide (CuBr, 99 %), copper (II) bromide (CuBr2, 98 %), and gelatin (Porcine skin, Type A) were obtained from Sigma-Aldrich Chemical Co. (St. Louis, MO), and were used without further purification. GMA was passed through a silica gel column to remove the inhibitor, and stored under a nitrogen atmosphere at −4 °C. All other chemical reagents and solvents were used as received. Human Umbilical Vein Endothelial cells (HUVECs, ATCC CRL-1730™) were purchased from American Type Culture Collection (Manassas, VA, USA). Cell culture medium (MCDB131), heparin and paraformaldehyde (4 %, v/v) were obtained from Sigma-Aldrich Chemical Co. Medium supplements, such as Foetal Bovine Serum (FBS), bovine brain extract, amphotericin, penicillin, streptomycin, and Trypsin–EDTA (0.25 %), were obtained from Life Technologies (Carlsbad, CA, USA). LIVE/DEAD® Cell Viability assays and AlamarBlue™ assay reagents were also purchased from Life Technologies. Dulbecco’s phosphate buffered saline (PBS, pH 7.4) solution was freshly prepared.
2.2 Preparation of Polycaprolactone Film and Aminolysis Process
Polycaprolactone (PCL) films were prepared by solution casting method. Five gram of the PCL pellets were dissolved in 40 ml of dichloromethane to form the PCL solution. The polymer solution was then cast onto the glass substrate with predetermined thickness using the automatic film applicator (PA-2105, BYK). The solvent was removed at room temperature by slow evaporation over a 24-h period, and was further dried in a vacuum oven for another 24 h at 35 °C to obtain translucent PCL films with a thickness of about 150 μm. The resultant pristine PCL films were cut into round-shaped specimens with a diameter of 2 cm, followed by washing with copious amount of deionized water and isopropanol. The films were dried in a vacuum oven at room temperature prior to use. The cleaned PCL films were subsequently aminolyzed to introduce amino groups onto the surface of PCL films using a procedure described previously [10, 20, 23]. Briefly, the PCL films were immersed in a 10 % (w/w) isopropanol solution of 1,6-hexanediamine at 40 °C for 10 min, 30 min, 1 h, 1.5 h, 2 h, and 3 h. After aminolysis treatment, the PCL films were thoroughly rinsed with copious amount of deionized water to remove free 1,6-hexanediamine, and dried in a vacuum oven at 30 °C for 24 h.
2.3 Immobilization of Gelatin onto the Aminolyzed PCL Film Surface
The aminolyzed PCL films from 1 h of aminolysis were immobilized with gelatin using glutaraldehyde (GA) as cross-linking agent in a two-step method, as shown schematically in scheme a of Scheme 1. In the first step, the PCL-NH2 films were immersed in a 2.5 wt % glutaraldehyde (GA)/PBS solution at room temperature for 12 h to produce the PCL-GA surface. The reaction was stopped by rinsing the samples rigorously with copious amount of deionized water to remove free GA. Subsequently, the resultant PCL-GA surface was incubated in 3 mg/ml gelatin/PBS solution at room temperature for 24 h under continuous stirring to form the PCL-gelatin surface. After the reaction, the gelatin-immobilized PCL films were washed thoroughly with copious amounts of deionized water, followed by immersion in a large volume of PBS solution for 24 h to ensure the complete removal of any physically adsorbed gelatin.
2.4 Surface-initiated ATRP of GMA and Conjugation of Gelatin
As shown schematically in scheme b of Scheme 1, the introduction of alkyl halide ATRP initiator on the PCL-NH2 surface was accomplished through the reaction of the amine groups with 2-bromoisobutyrate bromide (BIBB) . Briefly, the PCL-NH2 films were immersed in 30 ml of anhydrous hexane solution containing 1.0 ml (7.2 mmol) of triethylamine (TEA). After 30 min of degassing with nitrogen, the reaction mixture was cooled in an ice bath, and 0.89 ml (1.65 g, 7.2 mmol) of BIBB was added dropwise via a syringe. The reaction was allowed to proceed with gentle stirring at 0 °C for 2 h and then at room temperature for 12 h to give rise to the 2-bromoisobuty-immobilized PCL surface (the PCL-Br surface). The PCL-Br surface was washed thoroughly with copious amounts of hexane, ethanol, and finally deionized water, in that order, and was subsequently dried in a vacuum oven at room temperature overnight.
For the grafting of P(GMA) brushes from the PCL-Br film surfaces, surface-initiated ATRP of GMA was carried out using a [GMA (3 ml)]:[CuBr]:[CuBr2]:[Bpy] molar feed ratio of 100:1.0:0.2:2.0 in 5 ml of methanol/water mixture (5/1, v/v) at room temperature in a Pyrex® tube. The reaction was allowed to proceed for 0.5–3 h to generate the PCL-g-P(GMA) films. At the end of predetermined reaction time, the films were removed and washed thoroughly with methanol and deionized water to ensure the complete removal of the physical adsorbed reactants prior to being dried under vacuum. To directly couple gelatin onto the pendant epoxide groups, the PCL-g-P(GMA) films were incubated in 10 ml of the phosphate buffered saline (PBS, pH 7.4) containing 3 mg/ml gelatin. The coupling reaction was allowed to proceed at room temperature for 24 h under continuous stirring to produce the corresponding PCL-g-P(GMA)-c-gelatin surface. The physically adsorbed (reversibly bound) gelatin was desorbed in a large volume of PBS over 24 h at room temperature with gentle stirring, followed by rinsing with copious amounts of PBS and deionized water, respectively.
2.5 Determination of Grafting Density of Polymer Brushes and Conjugated Gelatin
2.6 Characterization of Surface-Functionalized PCL films
Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), atom force microscopy (AFM), and water contact angle (WCA) were used to characterize the surface properties of the functionalized PCL films. Detailed procedures for all measurements are described in the Supporting Information section.
2.7 Human Umbilical Vein Endothelial Cell (HUVEC) Culture
Human Umbilical Vein Endothelial Cells (HUVECs, ATCC CRL-1730TM) were cultured in gelatin-coated T25 flasks containing MCDB131 cell culture medium, supplemented with Foetal Bovine Serum, 0.2 % Bovine Brain Extract, 0.25 μg/ml amphotericin, 0.1 mg/ml heparin, 100 U/ml penicillin, and 100 μg/ml streptomycin, in a CO2 environment at 37 °C. The MCDB131 medium was changed every other day. Upon 90 % confluency, cells were harvested by trypsinization by 0.25 % Trypsin–EDTA. HUVECs between passages 4–6 were used for subsequent experiments.
2.8 Cell Adhesion and Proliferation
Cell viability and proliferation were determined using the AlamarBlue™ (AB) assay. 0.5 ml of HUVECs cell suspension (2 × 104 cells/ml) were seeded into each well of a 24-well plate containing the pristine and functionalized PCL films, and incubated in a 5 % CO2 environment at 37 °C for 1, 3, 5 and 7 days. The cell culture medium was changed every other day. At the end of each incubation period, culture medium was removed from the wells, and 0.5 ml of the AB solution (10 % AB solution in culture media without FBS) was added to the wells. The plates were incubated in a 5 % CO2 atmosphere at 37 °C for 4 h and the fluorescence density was measured using a microplate reader (Model 680, Bio-Rad Laboratories, Inc. Hercules, CA, USA) at an excitation wavelength of 570 nm and an emission wavelength of 580 nm. Cell numbers were calculated by seeding known quantities of cells and correlation with fluorescence emission.
2.9 Cell Imaging
In vitro qualitative analysis of cell coverage and viability was performed using the LIVE/DEAD® viability/cytotoxicity assay to assess the extent of endothelialisation on the functionalised PCL surfaces. For this procedure, calcein AM (4 mM in anhydrous dimethyl sulfoxide, DMSO) and EthD-1 (2 mM in DMSO/H2O, 1:4 v:v) were added to PBS (1:1,000 ratio) to produce a LIVE/DEAD® staining solution. The cell-seeded PCL samples, obtained after 7 days of cell culture, were first washed thrice with PBS to eliminate the nonadherent cells, followed by staining using 0.1 ml of LIVE/DEAD staining solution. After incubation in a 5 % CO2 atmosphere at 37 °C for 30 min, the samples were visualised with a Nikon Image Ti fluorescence microscope (emission at 515 nm and 635 nm (Nikon Instruments, Tokyo, Japan) to acquire fluorescent images using NIS-Elements Br software.
2.10 Statistical Analysis
All the quantitative results were expressed as mean ± standard deviation (SD). Statistical analysis was carried out by means of one-way analysis of variance (ANOVA) with Tukey’s post hoc test. A p value less than 0.05 was considered statistically significant.
3 Results and Discussion
3.1 Aminolysis of PCL Film Surface
Reaction time, grafting yield, and surface composition of the pristine PCL and surface-functionalized PCL surfaces
Reaction time (h)
GY (μg/cm2) (mean ± SD)
PCL-NH 2 b
0.42 ± 0.11
3.17 × 10−2
2.72 ± 0.68
2.34 × 10−2
6.31 ± 1.32
9.29 × 10−3
14.76 ± 2.63
4.72 × 10−3
0.93 ± 0.25
2.63 ± 0.52
3.79 ± 0.73
3.2 Immobilization of Gelatin onto the Aminolyzed PCL Surfaces
In this study, a monolayer of gelatin was immobilized onto the PCL-NH2 surface with glutaraldehyde (GA) as the cross-linking agent. The resulting surface is referred to as the PCL-gelatin surface. Figure 2d shows the FTIR spectrum of pure gelatin with characteristic peaks for ν(O–H) (3,400 cm−1), ν(N–H) (3,246 cm−1), amide I (1,642 cm−1) and amide II (1,543 cm−1) . Consequently, the successful immobilization of gelatin onto the PCL-NH2 surface could be deduced by the presence of a broad band at 3,295 cm−1, which is due to the overlap of free O–H and N–H stretching vibrations, and by the increase in relative intensity of the amide I band (1,650 cm−1) (Fig. 2c). The immobilized amount of gelatin for the PCL-gelatin surface, 0.42 ± 0.11 μg/cm2 (Table 1), was found to be similar to results obtained by other researchers [20, 23].
3.3 Surface-Initiated ATRP of GMA and Immobilization of Gelatin
For the grafting of polymer brushes via surface-initiated ATRP, a uniform layer of initiators immobilized on the PCL film surface is indispensible . The introduction of an alkyl bromide ATRP initiator was achieved via a TEA-catalyzed condensation reaction between the amine groups of the PCL-NH2 surface and 2-bromoisobutyryl bromide (BIBB). Successful immobilization of an alkyl bromide-containing ATRP initiator onto the PCL-NH2 surface could be deduced from the appearance of three additional signals of Br 3d (BE, 70 eV), Br 3p (BE, 189 eV), and Br 3 s (BE, 256 eV) in the wide scan spectrum of the PCL-Br surface (Fig. 3c) , as compared to that of the PCL-NH2 film (Fig. 3b). The [Br]/[C] ratio, as determined from the Br 3d and C 1 s core-level spectral area ratio, was found to be about 3.17 × 10−2 (Table 1). Thus, the alkyl bromine groups were successfully immobilized onto the PCL-NH2 surface in preparation for the subsequent ATRP process.
Poly(glycidyl methacrylate) (P(GMA) is an effective spacer for biomolecules, such as the immobilization of proteins, antibodies and enzymes, for tissue engineering applications . As such, the nucleophilic reaction between –NH2 moieties of biomolecules and epoxide groups has been widely reported [45, 46]. Therefore, PCL-g-P(GMA) surfaces with terminal halide groups and a high density of epoxide groups are well-suited for the immobilization of gelatin. In this work, the gelatin immobilized P(GMA)-grafted PCL substrates are defined as the PCL-g-P(GMA)0-c-gelatin, PCL-g-P(GMA)1-c-gelatin and PCL-g-P(GMA)2-c-gelatin surfaces, respectively. Figure 4c and d show the ATR-FTIR spectra of the PCL-g-P(GMA)1-c-gelatin and PCL-g-P(GMA)2-c-gelatin surfaces, respectively. The appearance of three additional bands at 3,295, 1,642, and 1,543 cm−1, attributable to the overlap of free O–H and N–H stretching, amide I and amide II, is associated with the coupling of gelatin on the film surfaces, as compared to the spectra of pure gelatin and the PCL-g-P(GMA) surfaces.
The [N]/[C] ratio, determined from the sensitivity factor-corrected N 1 s and C 1 s core-level spectral area, is used to assess the relative amount of immobilized gelatin. The [N]/[C] ratios of the PCL-g-P(GMA)0-c-gelatin, PCL-g-P(GMA)1-c-gelatin and PCL-g-P(GMA)2-c-gelatin surfaces were found to be about 0.134, 0.169 and 0.202 (Table 1) respectively, indicating that the P(GMA) brushes from 3 h of ATRP possess higher binding capability to gelatin. Earlier studies have reported that the concentration of epoxide groups of the grafted P(GMA) brushes played a dominant role in the immobilization of biomolecules . The immobilized gelatin amounts of 0.93 ± 0.25, 2.63 ± 0.52 and 3.79 ± 0.73 μg/cm2 (Table 1) for the PCL-g-P(GMA)0-c-gelatin, PCL-g-P(GMA)1-c-gelatin and the PCL-g-P(GMA)2-c-gelatin films respectively, showed that the amount of the immobilized gelatin is tunable by varying the concentration of epoxide groups on the P(GMA) brushes.
3.4 Surface Wettability and Topography
Surface roughness, surface wettability and cell adhesion on the pristine PCL and surface-functionalized PCL surfaces
Surface roughness (R a a , mean ± SD nm)
Cell adhesion ratiob (%)
Surface wettability (°)
Representative images of WCAc
19.3 ± 1.7
49.1 ± 7.2
93 ± 4
30.2 ± 4.5
63.0 ± 4.4
66 ± 3
34.5 ± 1.8
116.1 ± 3.5
49 ± 3
56.9 ± 4.4
50.1 ± 3.3
62 ± 3
59.4 ± 2.9
53.2 ± 4.0
61 ± 2
67.8 ± 6.2
127.2 ± 3.8
37 ± 2
72.3 ± 3.6
134.4 ± 4.4
35 ± 3
The changes in topography of the PCL film surfaces after each functionalization step were investigated by AFM. The surface roughness and the corresponding three-dimensional (3D) AFM images of the pristine and functionalized PCL films are shown in Table 2 and Fig. S3 (Supporting Information). The pristine PCL film surface was found to be relatively uniform and smooth with a root-mean-square surface roughness value (Ra) of about 19 ± 2 nm. A significant increase in the Ra value of 31 ± 5 nm was observed after the aminolysis treatment. This result is in agreement with the findings by other groups . After the immobilization of gelatin monolayer, no further significant difference in the Ra value was observed. After graft polymerization of GMA, the Ra values increased significantly to about 57 ± 4 nm (for the PCL-g-P(GMA)1) and 68 ± 3 nm (for the PCL-g-P(GMA)2 surfaces), respectively. The subsequent coupling of gelatin to P(GMA)-grafted films resulted in a further increase in the Ra values to 59 ± 2 nm (for the PCL-g-P(GMA)1-c-gelatin surface) and 71.5 ± 3 nm (for the PCL-g-P(GMA)2-c-gelatin surface).
3.5 Cell Adhesion
The interaction of cells with different PCL substrates was investigated by seeding endothelial cells (ECs) onto the films for 24 h to determine the initial adhesion ratios. Gelatin-coated coverslips were used as a positive control. The results (Table 2) showed that the ECs had the least affinity for the pristine PCL film, since less than 50 % of the total number of cells initially seeded onto the film remained on the film after 24 h. Despite obvious changes in surface hydrophilicity and roughness achieved after aminolysis treatment and the grafting of P(GMA) brushes, no significant improvement in cell adhesion ratio was observed on the PCL-NH2 and the P(GMA)-grafted surfaces, as compared to the pristine PCL surfaces, this suggests that other factors (e.g. biological cues) may be required for positive cell interaction. This hypothesis is confirmed by the fact that the gelatinized films (PCL-gelatin film) had a higher affinity for cells, as compared to the films that did not contain the bioactive components of gelatin. More evident improvement in cell adhesion was observed in the PCL-g-P(GMA)1-c-gelatin and PCL-g-P(GMA)2-c-gelatin surfaces (Table 2). In fact, the number of attached cells increased with increasing concentration of exposed gelatin on the PCL surface. As a result, the PCL-g-P(GMA)2-c-gelatin surface, which had the highest density of immobilized gelatin, exhibited the most significant increase in cell adhesion ratio, comparable to that of the gelatin-coated coverslips (positive controls).
As compared to the PCL-gelatin films, the PCL-g-P(GMA)-c-gelatin films had a higher amount of immobilized gelatin, since gelatin was directly coupled to the pendant epoxide group of the repeat unit of P(GMA) brushes, resulting in the immobilized gelatin appearing in a dispersed form among the grafted P(GMA) chains rather than in the formation of a continuous surface layer. The increase in cell adhesion ratio of the PCL-g-P(GMA)2-c-gelatin surface (3.79 ± 0.73 μg/cm2) with respect to the PCL-g-P(GMA)1-c-gelatin surface (2.63 ± 0.52 μg/cm2) suggests that the cell adhesion is positively correlated to the amount of immobilized gelatin.
3.6 Cell Proliferation
In the case of the gelatin-immobilized film surfaces, ECs were observed to adopt a flat and spreading morphology (Figs. S6c and 6e), which resulted in the formation of a confluent cell layer (Fig. S6f). Cell proliferation on the gelatin-immobilized surfaces was not only significantly enhanced, but was also found to be positively correlated to the amount of covalently immobilized gelatin. Despite the low surface density of immobilized gelatin for the PCL-gelatin films (about 0.42 ± 0.11 μg cm−1), a 13- and fivefold improvement in cell proliferation, as compared to the pristine PCL and the PCL-NH2 surfaces respectively, was observed. With the increase in surface density of immobilized gelatin, more pronounced enhancements in cell proliferation were observed for the PCL-g-P(GMA)1-c-gelatin and PCL-g-P(GMA)2-c-gelatin surfaces as compared to the PCL-gelatin surface. Moreover, the proliferation rate of the ECs on the PCL-g-P(GMA)2-c-gelatin surface was higher than that of the PCL-g-P(GMA)1-c-gelatin surface. In fact, the results obtained for the PCL-g-P(GMA)1-c-gelatin and PCL-g-P(GMA)2-c-gelatin surfaces were comparable to those of the gelatin-coated coverslips (positive controls), which showed that in general, the presence of immobilized gelatin led to an overall positive effect on cell proliferation.
3.7 Cell Imaging
3.8 Stability of Gelatin-Immobilized Surface
The stability of the grafted gelatin-coupled P(GMA) layers on the PCL substrate surface was investigated, as this had direct influence over the long-term viability of the functionlized substrates. In previous studies, surface-initiated ATRP-grafted polymer brushes on various substrates, including glass, fiber, paper, silicon wafer and titanium, were shown to be stable under harsh environments [33–37]. For this study, the gelatin molecules were immobilized directly onto the side chains of P(GMA) brushes via robust covalent bonding (O=CNH), which led to the formation of highly stable gelatinized surfaces.
However, to further investigate the possible release of gelatin from the side chains of the P(GMA) brushes, the gelatin-immobilized PCL substrates were immersed in 50 ml of the PBS solution at 25 °C for 10 days under slight agitation. After 10 days, the gelatin-immobilized substrates were washed vigorously with deionized water and dried under reduced pressure prior to XPS characterization. The XPS results (Supporting Information, Fig. S7) showed that the composition of the PCL-g-P(GMA)-c-gelatin surface remained relatively unchanged even after immersion in the PBS solution, as seen from the [N]/[C] ratios for the PCL-g-P(GMA)1-c-gelatin and PCL-g-P(GMA)2-c-gelatin substrates before and after immersion. The results therefore confirm the high stability of the gelatin on the P(GMA) brushes.
PCL substrates were successfully modified via the conventional chemical immobilization process and surface-initiated ATRP of GMA. Kinetics studies revealed an approximately linear increase in grafting yield of the functional P(GMA) brushes using the ATRP process with polymerization time, and that the amount of immobilized gelatin on the P(GMA) chains increased with the pendant epoxide concentration of the grafted P(GMA) brushes. Subsequent in vitro cell adhesion and proliferation studies using HUVECs revealed better cell affinity and growth on the gelatin-immobilized PCL film surface, as compared to the poor performance of the pristine PCL and aminolyzed PCL film surfaces. Cell proliferation was also found to be positively correlated with the surface density of the immobilized gelatin, which was why the PCL-g-P(GMA)2-c-gelatin substrates showed significantly improved cell attachment properties as compared to the other gelatinized substrates. With the inherent versatility of surface-initiated ATRP, and the good cell-adhesive nature of gelatin, biodegradable polyesters can be readily tailored with high surface concentrations of gelatin to facilitate rapid endothelialization for cardiovascular applications. The approach described in this study can potentially be used for other bioactive molecules to improve cell–material interactions of biodegradable polyester polymers currently used for biomedical applications.
This research is supported by the Singapore National Research Foundation under CREATE programme: The Regenerative Medicine Initiative in Cardiac Restoration Therapy (NRF-Technion).
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