Biomedical subjects

J Feijen

Publications and source records attributed to J Feijen.

At least 73 records · Page 4Linked to original sources

PubMed1999

Crosslinking and modification of dermal sheep collagen using 1, 4-butanediol diglycidyl ether.

Crosslinking of dermal sheep collagen (DSC) was accomplished using 1, 4-butanediol diglycidyl ether (BDDGE). At pH values > 8.0, epoxide groups of BDDGE will react with amine groups of collagen. The effects of BDDGE concentration, pH, time, and temperature were studied. Utilization of a 4-wt % BDDGE instead of 1-wt % resulted in a faster reaction. Whereas similar values of shrinkage temperature were obtained, fewer primary amine groups had reacted at a lower BDDGE concentration, which implies that the crosslinking reaction had a higher efficacy. An increase in pH from 8.5 to 10.5 resulted in a faster reaction but reduced crosslink efficacy. Furthermore, an increase in reaction temperature accelerated the reaction without changing the crosslink efficacy. Crosslinking under acidic conditions (pH < 6.0) evoked a reaction between epoxide groups and carboxylic acid groups of collagen. Additional studies showed that no oligomeric crosslinks could be formed. However, hydrolysis of the epoxide groups played a role in the crosslink mechanism especially under acidic reaction conditions. The macroscopic properties of these materials were dependent on the crosslinking method. Whereas a flexible and soft tissue was found if crosslinking was performed at pH < 6.0, a stiff sponge was obtained under alkaline conditions. Reaction of DSC with a monofunctional compound (glycidyl isopropyl ether) led to comparable trends in reaction rate and in similar macroscopical differences in materials as observed with BDDGE.

Animals↗

PubMed1999

Proliferation of endothelial cells on surface-immobilized albumin-heparin conjugate loaded with basic fibroblast growth factor.

Seeding of endothelial cells (ECs) on the luminal surface of small-diameter vascular grafts is a promising method to avoid occlusion of these prostheses. Immobilization of basic fibroblast growth factor (bFGF) to substrates used to coat or fill porous prostheses may enhance the formation of a confluent monolayer of ECs. Human umbilical vein endothelial cells (HUVECs) were grown on bFGF-loaded albumin-heparin conjugate bound to CO2 gas-plasma-treated polystyrene. In the order of 2-3 ng/cm2 bFGF had to be immobilized to form a confluent monolayer of HUVECs. The most prominent effect of surface-immobilized bFGF was stimulation of the proliferation shortly after seeding, resulting within 3 days in confluent cell monolayers with high density. In contrast, in cultures with 0.3 ng/mL bFGF in the medium instead of bFGF bound to the surface, it took almost a week before the cell layers reached confluency. Binding of bFGF to heparin and the biological activity of bFGF towards ECs were not influenced by the (radio-)labeling of bFGF with iodine. However, only a minor part of the bFGF used in this study displayed heparin affinity. Furthermore, degradation and multimerization of labeled bFGF in time occurred when the growth factor was stored at 20 degrees -37 degrees C. This limits the use of labeled bFGF to short-term (hours) experiments. In conclusion, bFGF loading of vascular graft surfaces through complexation of bFGF with a heparin-containing matrix probably will lead to more rapid formation of a confluent monolayer of ECs on graft surfaces upon seeding of the cells.

Blood Vessel Prosthesis↗

PubMed1999

Characterization and biocompatibility of epoxy-crosslinked dermal sheep collagens.

Dermal sheep collagen (DSC), which was crosslinked with 1, 4-butanediol diglycidyl ether (BD) by using four different conditions, was characterized and its biocompatibility was evaluated after subcutaneous implantation in rats. Crosslinking at pH 9.0 (BD90) or with successive epoxy and carbodiimide steps (BD45EN) resulted in a large increase in the shrinkage temperature (T(s)) in combination with a clear reduction in amines. Crosslinking at pH 4.5 (BD45) increased the T(s) of the material but hardly reduced the number of amines. Acylation (BD45HAc) showed the largest reduction in amines in combination with the lowest T(s). An evaluation of the implants showed that BD45, BD90, and BD45EN were biocompatible. A high influx of polymorphonuclear cells and macrophages was observed for BD45HAc, but this subsided at day 5. At week 6 the BD45 had completely degraded and BD45HAc was remarkably reduced in size, while BD45EN showed a clear size reduction of the outer DSC bundles; BD90 showed none of these features. This agreed with the observed degree of macrophage accumulation and giant cell formation. None of the materials calcified. For the purpose of soft tissue replacement, BD90 was defined as the material of choice because it combined biocompatibility, low cellular ingrowth, low biodegradation, and the absence of calcification with fibroblast ingrowth and new collagen formation.

Animals↗

PubMed1999

Successive epoxy and carbodiimide cross-linking of dermal sheep collagen.

Cross-linking of dermal sheep collagen (N-DSC, T(S) = 46 degrees C, number of amine groups = 31 (n/1000)) with 1,4-butanediol diglycidyl ether (BDDGE) at pH 9.0 resulted in a material (BD90) with a high T(S)(69 degrees C), a decreased number of amine groups of 15 (n/1000) and a high resistance towards collagenase and pronase degradation. Reaction of DSC with BDDGE at pH 4.5 yielded a material (BD45) with a T(S) of 64 degrees C, hardly any reduction in amine groups and a lower stability towards enzymatic degradation as compared to BD90. The tensile strength of BD45 (9.2 MPa) was substantially improved as compared to N-DSC (2.4 MPa), whereas the elongation at break was reduced from 210 to 140%. BD90 had a tensile strength of 2.6 MPa and an elongation at break of only 93%. To improve the resistance to enzymes and to retain the favorable tensile properties, BD45 was post-treated with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) in the presence of N-hydroxysuccinimide (NHS) to give BD45EN. Additional cross-linking via the formation of amide bonds took place as indicated by the T(S) of 81 degrees C and the residual number of amine groups of 19 (n/1000). BD45EN was stable during exposure to both collagenase and pronase solutions. The tensile properties (tensile strength 7.2 MPa, elongation at break 100%) were comparable to those of BD45 and glutaraldehyde treated controls (G-DSC). Acylation of the residual amine groups of BD45 with acetic acid N-hydroxysuccinimide ester (HAc-NHS) yielded BD45HAc with a large reduction in amine groups to 10 (n/1000) and a small reduction in T(S) to 62 degrees C. The stability towards enzymatic degradation was reduced, but the tensile properties were comparable to BD45.

Animals↗

PubMed1999

Adsorption of proteins from plasma at polyester non-wovens.

Polyester non-wovens in filters for the removal of leukocytes from platelet concentrates (PCs) must be platelet compatible. In PC filtration, the adsorption of proteins at the plasma-non-woven interface can be of great importance with respect to the yield of platelets. Unmodified and radio frequency glow discharge (RFGD) treated poly(ethylene terephthalate) non-woven (NW-PET) and two commercial surface-modified non-wovens were contacted with human plasma. Protein desorption by sodium dodecyl sulphate (SDS) was evaluated by X-ray photoelectron spectroscopy (XPS). The desorbed proteins were characterized by gel electrophoresis and immunoblotting. Compared to the commercial surface-modified non-wovens, unmodified and RFGD-treated NW-PETs adsorbed a relatively high amount of protein. Significantly more protein was removed from the hydrophobic NW-PET by SDS than from the hydrophilic RFGD-treated non-wovens. RFGD treatment of NW-PET reduces the reversibility of protein adsorption. Less albumin and fibrinogen were removed from the RFGD-treated non-wovens than from NW-PET. In addition, a large amount of histidine-rich glycoprotein was removed from RFGD-treated non-wovens, but not from NW-PET. The different behaviour of RFGFD-treated non-wovens towards protein adsorption is probably caused by differences in the chemical reactivity of the non-woven surfaces.

Adsorption↗

PubMed1999

Initial adhesion and surface growth of Pseudomonas aeruginosa on negatively and positively charged poly(methacrylates).

The infection risk of biomaterial implants is determined by an interplay of bacterial adhesion and surface growth of the adhering organisms. In this study, we compared initial adhesion and surface growth of Pseudomonas aeruginosa AK1 (zeta potential -7 mV) on negatively charged (PMMA/MAA, zeta potential -18 mV) and positively charged (PMMA/TMAEMA-Cl, zeta-potential +12 mV) methacrylate copolymers in situ in a parallel plate flow chamber. Initial adhesion was measured using phosphate-buffered saline and subsequent surface growth of the adhering bacteria using nutrient broth as growth medium. Initial adhesion was twice as fast on the positively charged methacrylate than on the negatively charged copolymer. Surface growth, however, was absent on the positively charged copolymer, while on the negatively charged methacrylate the number of bacteria increased exponentially during surface growth with a generation time of 32 min. From the results of this study it can be concluded that positively charged biomaterial surfaces might show reduced risks of biomaterials-centred infections, despite being more adhesive.

Journal Article↗

PubMed1999

Formulation and lyoprotection of poly(lactic acid-co-ethylene oxide) nanoparticles: influence on physical stability and in vitro cell uptake.

PURPOSE: To investigate the feasibility of producing freeze-dried poly(ethylene oxide) (PEO)-surface modified nanoparticles and to study their ability to avoid the mononuclear phagocytic system (MPS), as a function of the PEO chain length and surface density. METHODS: The nanoparticles were produced by the salting-out method using blends of poly(D,L-lactic acid) (PLA) and poly(D,L-lactic acidco-ethylene oxide) (PLA-PEO) copolymers. The nanoparticles were purified by cross-flow filtration and freeze-dried as such or with variable amounts of trehalose as a lyoprotectant. The redispersibility of the particles was determined immediately after freeze-drying and after 12 months of storage at -25 degrees C. The uptake of the nanoparticles by human monocytes was studied in vitro by flow cytometry. RESULTS: PLA-PEO nanoparticles could be produced from all the polymeric blends used. Particle aggregation after freeze-drying was shown to be directly related to the presence of PEO. Whereas this problem could be circumvented by use of trehalose, subsequent aggregation was shown to occur during storage. These phenomena were possibly related to the specific thermal behaviours of PEO and trehalose. In cell studies, a clear relationship between the PEO content and the decrease of uptake was demonstrated. CONCLUSIONS: The rational design of freeze-dried PEO-surface modified nanoparticles with potential MPS avoidance ability is feasible by using the polymer blends approach combined with appropriate lyoprotection and optimal storage conditions.

Biodegradation, Environmental↗

PubMed1999

Endothelialization of crosslinked albumin-heparin gels.

Crosslinked gels of albumin as well as heparinized albumin gels, potential sealants of prosthetic vascular grafts, were studied with regard to in vitro stability, binding of basic fibroblast growth factor (bFGF) and cellular interactions. A small percentage of the heparin present in these gels, was released during storage in SDS solution. During storage in cell culture medium at 37 degrees C, heparin release was 21-25 percent. Release of albumin did not occur. Human umbilical vein endothelial cells (HUVECs) rapidly adhered and subsequently spread on (heparinized) albumin gels, but proliferation was only observed if heparin was present in the gel. Binding of 125I-bFGF to heparinized albumin gel was 35 percent higher than to non-heparinized albumin gel. Growth of HUVECs occurred only on heparinized albumin gel loaded with bFGF and not on bFGF-loaded albumin gel. The number of platelets deposited under stationary conditions onto heparinized albumin gel was about twice the number found on nonheparinized albumin gel. Seeding of HUVECs on heparinized albumin gel, significantly reduced the number of platelets adhering to this surface. Moreover, no spreading of platelets was observed on substrates seeded with HUVECs. It can be concluded that crosslinked gels of albumin to which heparin is immobilized, are candidate sealants for prosthetic vascular grafts and suitable substrates for endothelial cell seeding.

Albumins↗

PubMed1998

Controlled delivery of antibacterial proteins from biodegradable matrices.

Prosthetic valve endocarditis is an infrequent, but serious complication of cardiac valve replacement. The infection is caused by the adherence of bacteria to the prosthetic valve or to tissue at the site of implantation. Recently it was shown that antibacterial peptides from blood platelets are involved in clearance and killing of bacteria adhering to vegetations induced in a model for prosthetic valve endocarditis using rabbits. The application of these antibacterial proteins in a release system, incorporated in the Dacron sewing ring of the prosthetic heart valve would diminish the incidence of endocarditis. In this study a release system for small cationic proteins based on cross-linked gelatin was developed and characterised. Furthermore, the system was evaluated with respect to the uptake and in vitro release of lysozyme, a small cationic protein that was chosen as a model protein for small cationic antibacterial proteins. Variation of gelatin type (A and B), and cross-link density resulted in differences in swelling, thermal behaviour, and number of charged groups. Lysozyme uptake was proportional to swelling, but was governed by the number of anionic groups. The latter was also observed for the release profiles: when the amount of free carboxylic acids is higher (gelatin B compared to gelatin A), the lysozyme release lasts for a longer time period. The release into solidified agarose medium, as a model for heart muscle tissue, was measured. After 50 h, 40-100% of the lysozyme was released, which is in accordance with the aimed release period of 24-48 h. The adsorption experiments in vitro suggest an influence of the electrostatic interactions between lysozyme and gelatin. This hypothesis was validated with a mathematical model which takes both diffusion and adsorption interactions into account.

Animals↗

PubMed1998

Relevance of aquatic biodegradation tests for predicting degradation of polymeric materials during biological solid waste treatment.

The aquatic biodegradability of cellulose and cellulose acetate with degrees of substitution (d.s.) in the range of 1.5 to 3.0, was compared with the mineralization under laboratory controlled composting conditions. In line with previous observations, it was found that cellulose acetates with d.s. < or = 2.5 were readily mineralized to CO2 in the controlled composting test. The degradation rate was clearly affected by the degree of substitution (d.s. 1.5 > d.s. 2.5 > d.s. 3.0). Surprisingly, however, biodegradation of cellulose acetate materials was not observed in the aquatic Strum test. Modifications of the pH and the inoculum source in an attempt to improve the activity of fungi and actinomycetes in the aquatic environment, did not increase CO2-evolution. It is concluded that the relevance of modified Strum tests is limited for predicting complete biodegradation of polymeric materials during biological waste processing. For evaluation of the compostability of polymeric products or packaging materials, more relevant laboratory controlled composting tests should be used.

Actinomycetaceae↗

PubMed1998

Different growth behaviour of human umbilical vein endothelial cells and an endothelial cell line seeded on various polymer surfaces.

Major obstacles for successful application of endothelial cell seeding in synthetic vascular grafts include the source of autologous endothelial cells, the efficiency of cell seeding and detachment of adherent endothelial cells from the graft surface after restoration of circulation. Human umbilical vein endothelial cells (HUVECs) are frequently used to investigate the in vitro adhesion and proliferation of endothelial cells on polymer surfaces. In order to minimize the biological variation of HUVECs isolated from different umbilical veins, it would be advantageous to use an endothelial cell line in in vitro proliferation experiments. Aim of the present study was to compare the proliferation of primary HUVECs and the endothelial cell line EC-RF24 on several polymer surfaces coated with various concentrations of the adhesive protein fibronectin. EC-RF24 cells grow to a higher density than primary HUVECs. Moreover, the EC-RF24 cell line is able to proliferate on surfaces with sub-optimal adhesive properties. Therefore, it is concluded that the EC-RF24 cell line is less suitable for evaluation of the in vitro proliferation of endothelial cells on polymer surfaces.

Biocompatible Materials↗

PubMed1998

Small-diameter vascular graft prostheses: current status.

In contrast to large-diameter vascular grafts (i.e. larger than 5 mm) which remain excellent for more than 10 years after implantation, small-diameter vascular grafts of both Dacron and Teflon occlude rapidly upon implantation. In this overview article, the strategies used to improve the patency of these small-diameter grafts, the current status in clinical trials, and further perspectives in the field of artificial vascular graft development are reviewed. It is concluded that, in view of recent developments in tissue engineering approaches, the future of small-diameter vascular prostheses looks promising.

Animals↗

PubMed1998

Preparation of heparin-like surfaces by introducing sulfate and carboxylate groups on poly(ethylene) using an argon plasma treatment.

Carboxylate and sulfate groups were introduced at the surface of poly(ethylene) (PE) samples. This was accomplished by coating and immobilizing sodium 10-undecenoate (C11(:)) and 10-undecene sulfate (S11(:)) on the polymer by means of an argon plasma treatment. The composition of the coated surfactant layer was proportional to the composition of the coating solution. The thickness of the surfactant layer on the surface of PE samples, which were precoated from an aqueous solution with a total surfactant concentration of 0.30 M, was about 55 A. The presence of carboxylate and sulfate groups after plasma treatment of the precoated surfaces was confirmed by X-ray photoelectron spectroscopy (XPS). About 20% of the initial amount of functional groups of the coated surfactants was retained at the PE surface. The ratio of carboxylate/sulfate groups at the plasma treated surfaces was dependent on the composition of the precoated surfaces. The minimum surface density of these groups on the resulting samples was about one group per 40 A2.

Argon↗

PubMed1998

Adherence and proliferation of endothelial cells on surface-immobilized albumin-heparin conjugate.

Small-diameter vascular grafts rapidly fail after implantation, due to occlusion caused by thrombosis. This problem cannot be overcome using medication. A promising improvement of graft patency is the seeding of endothelial cells (EC) on the luminal surface of the vascular graft. Conjugates of albumin and heparin, which were developed to obtain nonthrombogenic coatings, could form an ideal coating for vascular grafts. Besides presenting anticoagulant function, heparin will bind proteins with cell adhesive properties, thus facilitating adherence of EC to the graft surface. EC were able to grow to confluency on CO(2) gas plasma-treated polystyrene (PS-CO(2)) coated with albumin-heparin conjugate. CO(2) gas plasma treatment resulted in the introduction of functional groups at the surface (e.g., hydroxyl, aldehyde, carboxylic acid, and epoxide groups). Addition of albumin-heparin conjugate to the functionalized surface in an aqueous solution with pH 8.2 yielded a stable monolayer of covalently bound conjugate. The number of cells adhering and proliferating on this surface was comparable to the number of cells on fibronectin-coated PS-CO(2). However, the structure and size of EC proliferating on surface-immobilized albumin-heparin was more irregular. Long-term adherence might be improved by adding fibronectin to the albumin-heparin surface, either as a mixture with albumin-heparin or in a separate incubation step.

Albumins↗

PubMed1997

In vitro evaluation of heparinized Cuprophan hemodialysis membranes.

Cuprophan hemodialysis membranes can be heparinized using N,N'-carbonyldiimidazole (CDI) as a coupling agent. In this study, the characteristics of heparinized Cuprophan membranes have been evaluated. After immobilization, heparin partially retained its biologic activity. An anticoagulant activity of 12.4 +/- 4.2 mU/cm2 was measured using a thrombin inactivation assay. Immobilized heparin also displayed an anti-complement activity. After contact with human serum; heparinized Cuprophan induced no generation of significant amounts of fluid phase terminal complement complex (TCC), whereas untreated Cuprophan induced the generation of substantial amounts of TCC. Heparinization did not affect the permeability of Cuprophan for model solutes with molecular weights up to 12,000 g/mol except for sulfobromophthalein sodium salt. The permeability of Cuprophan for sulfobromophthalein sodium salt was slightly decreased after heparinization. The ultrafiltration rate of Cuprophan increased by about 30% after heparinization, probably owing to an increased swelling of the membrane in water. Heparinized Cuprophan incubated in phosphate-buffered saline at 37 degrees C showed some release of heparin. These amounts of released heparin, however, were very low as compared to the amounts of heparin which are systemically administered during clinical hemodialysis treatment. It is concluded that Cuprophan membranes heparinized by means of the CDI-activation procedure are highly promising for application in hemodialyzers to be used for the treatment of patients with reduced or without systemic administration of heparin.

Cellulose↗

PubMed1997

Heparinization of gas plasma-modified polystyrene surfaces and the interactions of these surfaces with proteins studied with surface plasmon resonance.

Polystyrene surfaces obtained by spin-coating a solution of polystyrene in toluene on a gold layer were functionalized with carboxylic acid groups by preadsorption of the sodium salt of undecylenic acid, followed by an argon plasma treatment. A conjugate of albumin and heparin (alb-hep) was covalently immobilized onto the functionalized surface via preactivation of carboxylic acid groups with a water-soluble carbodiimide. The immobilization of alb-hep conjugate and the subsequent interactions of the heparinized surface with antithrombin III (ATIII, a heparin cofactor) and thrombin were monitored with surface plasmon resonance (SPR). The surface concentration of conjugate as determined with SPR deviated quantitatively from the results obtained with radiolabelled conjugate. The difference in surface concentrations of conjugate obtained with the two methods probably originates from the uncertainty of the refractive index of the alb-hep conjugate in the SPR technique. ATIII could be bound to the surface modified with alb-hep conjugate but not to a polystyrene surface modified with albumin. Rabbit anti-human ATIII did bind to the alb-hep surface previously exposed to ATIII, confirming the presence of surface bound ATIII. The alb-hep immobilized surface was able to bind much more thrombin than ATIII, which is probably due to the less specific heparin-thrombin interaction as compared to the heparin-ATIII interaction. This study shows that SPR is a technique that can be used to study, in real time, both the modification of polymer surfaces and the subsequent interactions of the modified surfaces with proteins.

Albumins↗

PubMed1997

Immobilization of functionalized alkyl-poly(ethylene oxide) surfactants on poly(ethylene) surfaces by means of an argon plasma treatment.

Alkyl-poly(ethylene oxide) (PEO) surfactants containing a terminal hydroxyl, sulfate, or carboxylate group were grafted at the surface of poly(ethylene) (PE) samples to improve their blood compatibility. Grafting was achieved by immobilizing PEO surfactants on PE using an argon plasma treatment. The sulfate group containing PEO surfactant was synthesized by sulfating polyoxyethylene(20)stearylether (Brij78; B) with chlorosulfonic acid. A carboxylate-terminated surfactant was synthesized by a substitution reaction of the sodium alkoxide form of B with sodium iodoacetate. XPS analysis of the modified PE samples showed that at short plasma treatment times of up to 5 s the structure of the immobilized surfactants is largely retained. When plasma treatment times longer than 30 s were applied, the PEO chains of the surfactants were degraded. The wettability of the modified PE samples was improved compared to the unmodified PE samples. The wettability of the modified samples did not change when they were stored in air at room temperature for at least 12 weeks.

Alkylation↗

PubMed1996

Effect of fibronectin on the binding of antithrombin III to immobilized heparin.

An objective of this research is to verify the mechanism of anticoagulant activity of surface-immobilized heparin in the presence of plasma proteins. The competition and binding interaction between immobilized heparin and antithrombin III (ATIII)/thrombin have been described in vitro. However, the strong ionic character of heparin leads to its specific and nonspecific binding with many other plasma proteins. Most notably, fibronectin contains six active binding sites for heparin which may interfere with the subsequent binding of heparin with ATIII or thrombin. Heparin was covalently immobilized through polyethylene oxide (PEO) hydrophilic spacer groups onto a model surface synthesized by random copolymerization of styrene and p-aminostyrene. The binding interaction of immobilized heparin with ATIII was then determined in the presence of different fibronectin concentrations. The binding interaction was studied by first binding immobilized heparin with ATIII, followed by the introduction of fibronectin; heparin binding with fibronectin, followed by incubation with ATIII, and simultaneous incubation of surface immobilized heparin with ATIII and fibronectin. The extent of ATIII binding to heparin in each experiment was assayed using a chromogenic substrate for ATIII, S-2238. The results of this study demonstrate that the displacement of ATIII from immobilized heparin was proportional to the fibronectin concentration, and was reversible. Furthermore, the binding sequence did not play a role in the final concentration of ATIII bound to immobilized heparin.

Anticoagulants↗