Effect of resin hydrophilicity and temperature on water sorption of dental adhesive resins

This study examined the effects of copolymer hydrophilicity and temperature on water sorption and solubility characteristics of five copolymer blends of increasing degree of hydrophilicity using gravimetric measurements. Six resin disks (15 mm in diameter x 1 mm in thickness) were prepared from each copolymer blend and were stored in deionised water at 23, 37 and 55 degrees C. Water sorption and solubility of the resin disks were measured before and after water immersion and desiccation. Multiple regression analysis of water sorption was performed on two independent variables, copolymer hydrophilicity and temperature. Maximum water sorption increased significantly with Hoy's total cohesive energy density (delta(t)), Hoy's solubility parameter for polar forces (delta(p)) and hydrogen bonding (delta(h)), but was not influenced by temperature. However, a significant positive relationship was observed between diffusion coefficients (obtained using Fick's law of diffusion) and temperature. The water absorption activation energy was 10 kJ/mol for the most hydrophilic copolymer blend R5 and 35-51 kJ/mol for copolymer blends R1-R4. The positive relationship between maximum water uptake and copolymer hydrophilicity suggests that water molecules diffuse through the polymer matrices by binding successively to the polar sites via hydrogen bonding. Such water sorption may determine the durability of resin-dentine bonds.     

Water-sorption kinetics of dental polymeric resin under tensile stressing conditions.

Water sorption tests were conducted on unfilled poly(methyl methacrylate) samples in distilled water at 5, 37, and 60 degrees C under three different tensile stress ratios (sigma appl/sigma ys = 0%, 5%, and 10%). Each sample was placed in a modified Hoffman open-side tubing clamp and subjected to four-point bending at pre-determined stress level for 1 day, 3 days, 1 week, 2 weeks, and 4 weeks. Water sorption was measured by weight change calculations, without accounting for any weight loss due to solubility of uncured monomer. A generalized diffusion equation can be used to express both stress-free and stress conditions; D = D0exp[-E (sigma)/kT]. It was found that the activation energy for water sorption diffusion was linearly related to applied stress ratios; i.e., E = 1.15 sigma appl/sigma ys + 10.76 (kJ/mol), with the correlation coefficient r = 0.97. Since the proportional pre-exponential constant, D0, is independent of temperature, it is speculated that the loading percentage of reinforcing filler elements in composite resin materials can be related to this constant.     

Effects of resin hydrophilicity on water sorption and changes in modulus of elasticity

As acidic monomers of self-etching adhesives are incorporated into dental adhesives at high concentrations, the adhesive becomes more hydrophilic. Water sorption by polymers causes plasticization and lowers mechanical properties. The purpose of this study was to compare the water sorption and modulus of elasticity (E) of five experimental neat resins (EX) of increasing hydrophilicity, as ranked by their Hoy's solubility parameters and five commercial resins. METHODS: After measuring the initial modulus of all resin disks by biaxial flexure, half the specimens were stored in hexadecane and the rest were stored in water. Repeated measurements of stiffness were made for 3 days. Water sorption and solubility measurements were made in a parallel experiment. RESULTS: None of the specimens stored in oil showed any significant decrease in modulus. All resins stored in water exhibited a time-dependent decrease in modulus that was proportional to their degree of water sorption. Water sorption of EX was proportional to Hoy's solubility parameter for polar forces (delta(p)) with increasing polarity resulting in higher sorption. The least hydrophilic resin absorbed 0.55 wt% water and showed a 15% decrease in modulus after 3 days. The most hydrophilic experimental resin absorbed 12.8 wt% water and showed a 73% modulus decrease during the same period. The commercial resins absorbed between 5% and 12% water that was associated with a 19-42% reduction in modulus over 3 days.     

Water absorption characteristics of dental microfine composite filling materials: II. Experimental materials

Water absorption characteristics have been studied in terms of diffusion coefficient equilibrium uptake, and solubility as a function of the volume loading of pyrolytic silica filler, for two different resins. Equilibrium uptake decreased with filler loading, but if calculated on the original volume of monomer present gave consistent values for each resin. Triethylene glycol dimethacrylate based materials had much higher water uptake and diffusion coefficients than the urethane dimethacrylate resins. Furthermore the former exhibited higher concentration dependance of the diffusion coefficient. Diffusion coefficients were sensibly independent of filler loading.     

Water sorption and mechanical properties of dental composites

The physical properties of four commercial dental composites were investigated through differential scanning calorimetry, water sorption and desorption measurements and flexural mechanical properties tests. The differential scanning calorimetry curves of samples as prepared and after different times of ageing in water indicated that the small residual monomer reactivity, present in the as prepared samples, disappeared after immersion in water, which probably acts as a plasticizer and facilitates a further crosslinking reaction of the material and the residual monomer desorption. Consistently, water causes the embrittlement of the material, as detected from the flexural mechanical properties. Water sorption and desorption kinetics were measured at different temperatures, the water diffusion coefficients were calculated and the activation energies of the diffusion process were determined. The SEM analysis of the fracture surfaces and the decrease of the water uptake on the temperature indicated the existence of a good filler/matrix adhesion.     

三种义齿软衬材料吸水性和溶解性的实验研究

我们对自凝水凝胶、自凝型丙烯酸酯和SDG－A硅橡胶三种义齿软衬材料进行吸水性和溶解性的实验探讨。采用的方法是将各材料制成直径50mm,厚1mm,表面平整光滑的园子,干燥24h后称重（m1）。再分别浸在人工唾液和蒸馏水溶液中保持7d和28d,称湿重（m2）,继续干燥后称重（m3）,最后计算材料的吸水值、吸水率和溶解率,统计学分析处理。结果显示：在人工唾液中7d和28d的吸水率,水凝胶为28.62%和24.96%,自凝型丙烯酸酯为1.89%和1.65%,SDG－A硅橡胶为0.25%和0.29%;溶解率分别为0.56%和0.51%,0.74%和0.83%,以及0.10%和0.12%。在蒸馏水中7d和28d的吸水率,水凝胶为30.15％和27.85％,自凝型丙烯酸酯为3.64％和6.17％,SDG－A硅橡胶为0.83％和0.98％;溶解率分别为0.79%和1.16%,0.86％和1.01％,以及0.10％和0.14％。结论是三种义齿软衬材料的吸水率大小依次为水凝胶＞丙烯酸酯＞硅橡胶。丙烯酸树脂由于含有一定量的增塑剂,其溶解率高于其他两种材料;浸泡溶液中增加离子成份可能对材料的吸水性能和溶解性能都有不同程度的影响;水凝胶材料的高吸水性能对临床实际意义还有等进一步研究。     

The influence of short-term water storage on the flexural properties of unidirectional glass fiber-reinforced composites

OBJECTIVE: The aim of this study was to determine flexural properties of unidirectional E-glass fiber-reinforced composite (FRC) with polymer matrices of different water sorption properties. METHODS: Rhombic polymer and FRC test specimens made of three commercially available diacrylate resin (Sinfony Activator, Triad Gel, 3M Scotchbond Adhesive) and different volume fractions of fibers were tested with three-point bending test according to ISO 10477 after storing in water for 30 days. Water sorption of specimens was also measured. RESULTS: Flexural strength of specimens with 45 vol% fraction E-glass fibers varied from 759 to 916 MPa in dry conditions. Water-stored specimens showed flexural strengths of 420-607 MPa. ANOVA analysis revealed that the fiber-volume fraction and the water sorption of the polymer matrix had a significant effect (p < 0.001) on the flexural properties. Dehydration of specimens recovered the mechanical properties. Decrease of flexural properties after water immersion was considered to be mainly caused by the plasticizing effect of water and the decrease depended on water sorption. SIGNIFICANCE: Use of polymers with low-water sorption seems to be beneficial in order to optimize the flexural properties of FRC.     

Sorption kinetics of ethanol/water solution by dimethacrylate-based dental resins and resin composites

In the present investigation the sorption-desorption kinetics of 75 vol % ethanol/water solution by dimethacrylate-based dental resins and resin composites was studied in detail. The resins examined were made by light-curing of bisphenol A glycol dimethacrylate (Bis-GMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), bisphenol A ethoxylated dimethacrylate (Bis-EMA), and mixtures of these monomers. The resin composites were prepared from two commercial light-cured restorative materials (Z100 MP and Filtek Z250), the resin matrix of which is based on copolymers of the above-mentioned monomers. Ethanol/water sorption/desorption was examined in both equilibrium and dynamic conditions in two adjacent sorption-desorption cycles. For all the materials studied, it was found that the amount of ethanol/water sorbed or desorbed was always larger than the corresponding one reported in literature in case of water immersion. It was also observed that the chemical structure of the monomers used for the preparation of the resins directly affects the amount of solvent sorbed or desorbed, as well as sorption kinetics, while desorption rate was nearly unaffected. In the case of composites studied, it seems that the sorption/desorption process is not influenced much by the presence of filler. Furthermore, diffusion coefficients calculated for the resins were larger than those of the composites and were always higher during desorption than during sorption. Finally, an interesting finding concerning the rate of ethanol/water sorption was that all resins and composites followed Fickian diffusion kinetics during almost the whole sorption curve; however, during desorption the experimental data were overestimated by the theoretical model. Instead, it was found that a dual diffusion-relaxation model was able to accurately predict experimental data during the whole desorption curve. Kinetic relaxation parameters, together with diffusion coefficients, are reported for all resins and composites.     

Water sorption characteristics of light-cured dental resins and composites based on Bis-EMA/PCDMA

The water uptake characteristics of resins and composites based on an ethoxylated bisphenol A glycol dimethacrylate (Bis-EMA) and a polycarbonate dimethacrylate (PCDMA) were studied in detail. Polydimethacrylate resins were prepared by photopolymerization of the neat monomers and mixtures of them with various weight ratios, using the camphoroquinone/N,N-dimethylaminoethyl methacrylate system as initiator, while the composites were prepared from the light-curing of commercial samples (Sculpt-It and Alert). Water sorption/desorption was examined both in equilibrium and dynamic conditions in two adjacent sorption-desorption cycles. The equilibrium water uptake from all resins was very small with a trend to increase as the amount of PCDMA was increased. The inverse effect was observed in the solubility values. The composites studied exhibited also very low water uptake values in comparison to other composite materials reported in the literature. It was also observed that the equilibrium uptake decreased with increasing filler loading. Slightly larger equilibrium water uptake and much smaller solubility values were obtained during the second sorption-desorption cycle in comparison to the first one. Concerning the sorption rate data, it was observed that the resin materials followed Fickian diffusion during almost the whole sorption or desorption curve, while the composites showed this behavior until only M(t)/M( infinity ) congruent with 0.5. The diffusion coefficients calculated for the resins were larger than those of the composites and always higher during desorption compared to sorption. The values of the diffusion coefficients for both resins and composites were in the same order of magnitude with the values of the corresponding materials reported in the literature.     

Sorption kinetics and equilibrium uptake for water vapor in soft-contact-lens hydrogels

A gravimetric-sorption technique was used to obtain kinetic and equilibrium adsorption/desorption data for water vapor in four different soft-contact-lens (SCL) polymers at 35 degrees C. The SCL materials are a conventional hydrogel (polymacon) with a low water content at saturation (<50 wt %); two conventional hydrogels (hilafilcon A and alphafilcon A) with a high water content at saturation (>50 wt %); and a siloxane hydrogel (balafilcon A). Absorption and desorption equilibrium isotherms (water activity versus water weight fraction) overlap at high water contents, whereas significant hysteresis is observed at low water contents. The hysteresis loop is likely due to trapping of water in the polymer during the desorption process because of a rubber-to-glass transition of the SCL-film surfaces. Sorption data were interpreted using Flory-Rehner theory. The positive Zimm and Lundberg cluster function suggests that water tends to cluster in these SCL materials, except at very low water content. For polymacon and hilafilcon A, Fickian diffusion is observed for all activities for both water sorption and desorption. However, for alphafilcon A and balafilcon A, non-Fickian features appear at intermediate/low activities, in particular during water desorption, suggesting coupling of the diffusion process with polymer-matrix relaxation. The diffusion coefficient increases significantly with water concentration for polymacon and hilafilcon A (from approximately 0.3 x 10(-8) to 4.0 x 10(-8) cm2/s) because of augmented mixture free volume induced by water sorption, whereas a more complex composition dependence is observed for alphafilcon A and balafilcon A probably as consequence of a combined effect of polymer relaxation, plasticization, and water clustering.     

Water sorption and solubility of contemporary resin-based filling materials

PURPOSE: Evaluation of water sorption and solubility of contemporary resin-based filling materials. METHODS: Specimens of Herculite (HE), Point 4 (P4), TetricCeram (TC), Miris (MI), TetricCeram HB (HB), Solitaire 2 (SO), SureFil (SU), Definite (DE), Admira (AD), Dyract AP (DY), Compoglass F (CO), and TetricFlow (TF) were prepared according to ISO 4049. Water sorption and solubility were measured after water storage at 37 degrees C for 7 days. RESULTS: Water sorption was HE 14 microg mm(-3), P4 17 microg mm(-3), TC 12 microg mm(-3), MI 13 microg mm(-3), HB 9 microg mm(-3), SO 18 microg mm(-3), SU 9 microg mm(-3), DE 14 microg mm(-3), AD 27 microg mm(-3), DY 19 microg mm(-3), CO 23 microg mm(-3), and TF 19 microg mm(-3). Solubility was HE 3 microg mm(-3), P4 3 microg mm(-3), TC 1 microg mm(-3), MI 0 microg mm(-3), HB 0 microg mm(-3), SO 3 microg mm(-3), SU 0 microg mm(-3), DE 1 microg mm(-3), AD 2 microg mm(-3), DY 4 microg mm(-3), CO -2 microg mm(-3), and TF 1 microg mm(-3). CONCLUSION: All materials met the corresponding requirement in ISO 4049. Filler load negatively correlated with water sorption but not with solubility. There was an influence of the resin matrix, too. No significant differences were found between composites, ormocers, and compomers.     

Sorption and solubility testing of orthodontic bonding cements in different solutions

To evaluate and compare the solubility and sorption of orthodontic bonding cements after immersion in different solutions, five different cements were used: a fluoride-containing resin composite, a light-cured glass ionomer cement, a light-cured resin composite, a paste-paste chemically cured resin composite, and a liquid-paste chemically cured resin composite. Five different solutions were employed: distilled water, artificial saliva, an alcohol-free mouthrinse solution (Orthokin), a 5% alcohol mouthrinse solution (Perioaid), and a 75% ethanol/water solution. Five disc specimens (15 mm x 0.85 mm) were used for each experimental condition. Materials were handled following manufacturers' instructions and were ground wet with silicon carbide paper. Solubility and sorption of the materials were calculated by means of weighing the samples before and after immersion and desiccation. Data were analyzed by two-way ANOVA and Student-Newman-Keuls test (p < 0.05). The light-cured glass ionomer cement showed the lowest solubility and the highest sorption values. When using alcohol-containing solutions as storage media, solubility of the paste-paste chemically cured resin composite increased, and sorption values for the tested chemically cured resin composites were also increased. The use of alcohol-free mouthrinses does not affect sorption and solubility of orthodontic cements. The chemically cured (paste-paste) composite resin cement, requiring a mixing procedure, was the most affected by immersion in alcohol-containing solutions.     

The relationship between water absorption characteristics and the mechanical strength of resin-modified glass-ionomer cements in long-term water storage.

The purpose of this study is to elucidate the water absorption characteristics of resin-modified glass-ionomer cements and to also investigate the relationship between the characteristics and mechanical strength after long-term water storage. The mechanism of water diffusion in these cements is also discussed. Water absorption was measured using a gravimetric analysis for 12 m, while the diffusion coefficient was calculated using Fick's law of diffusion. Water solubility was determined based on the weight of the residue in the immersed water. The compressive and diametral tensile strength were measured at 1, 2, 6, and 12 m. A correlation was observed between the diffusion coefficient and equilibrium water uptake, which thus suggests the water in the cements to diffuse through micro-voids in accordance with the 'Free volumetric theory'. A correlation was seen between the solubility and diffusion coefficient of the cements. The deterioration ratio, defined as the ratio of the strength at 12 m versus that at 1 m, was also calculated. Finally, a negative correlation was observed between the deterioration ratio of the compressive strength and the diffusion coefficients of the cements.     

The water equivalence of solid materials used for dosimetry with small proton beams

Various solid materials are used instead of water for absolute dosimetry with small proton beams. This may result in a dose measurement different to that in water, even when the range of protons in the phantom material is considered correctly. This dose difference is caused by the diverse cross sections for inelastic nuclear scattering in water and in the phantom materials respectively. To estimate the magnitude of this effect, flux and dose measurements with a 177 MeV proton pencil beam having a width of 0.6 cm (FWHM) were performed. The proton flux and the deposited dose in the beam path were determined behind water, lucite, polyethylene, teflon, and aluminum of diverse thicknesses. The number of out-scattered protons due to inelastic nuclear scattering was determined for water and the different materials. The ratios of the number of scattered protons in the materials relative to that in water were found to be 1.20 for lucite, 1.16 for polyethylene, 1.22 for teflon, and 1.03 for aluminum. The difference between the deposited dose in water and in the phantom materials taken in the center of the proton pencil beam, was estimated from the flux measurements, always taking the different ranges of protons in the materials into account. The estimated dose difference relative to water in 15 cm water equivalent thickness was -2.3% for lucite, -1.7% for polyethylene, -2.5% for teflon, and -0.4% for aluminum. The dose deviation was verified by a measurement using an ionization chamber. It should be noted that the dose error is larger when the effective point of measurement in the material is deeper or when the energy is higher.     

Water sorption, solubility and effect of post-curing of glass fibre reinforced polymers.

Different polymer matrices are used for dental glass fibre composites. The aims of this study were to determine water sorption and solubility of glass fibre composites with different polymer matrices. In addition, the effect of post-curing of matrix polymers with heat on the water sorption and solubility values was investigated. Commercial one-phase and two-phase (powder-liquid) monomer systems were used in polymer matrix of E-glass fibre composite. Rhombic unreinforced and fibre reinforced test specimens were polymerized by autopolymerization or by light only, or additionally post-cured with heat. Water sorption and solubility determination method was based on ISO/DIS 1567-1997 draft for international standard with 7 d immersion time. In addition, water sorption was measured at second time for 30 d immersion time to determine saturation time of test specimens by water. Five test specimens of unreinforced polymer and reinforced polymer were tested and the quantity of fibres was determined by combustion analysis. Water sorption values of different brands of polymer matrices ranged from 0.9 to 8.3 wt% (P < 0.001, ANOVA). High sorption values were explained by microscopic voids in the polymer matrix and by composition of polymer matrix. Solubility values ranged from 0.02 to 2.5 wt% (P < 0.001, ANOVA). Generally, fibre inclusion and post-curing of polymer matrix reduced water sorption and solubility. The results of this study suggest that the water sorption and solubility of fibre composites varies according to the brand of polymer matrix and homogenity of polymer matrix. Water sorption of polymer matrix might influence hydrolytic stability of polymer-glass fibre composite.     

Temperature dependence of HU values for various water equivalent phantom materials

The temperature dependence of water equivalent phantom materials used in radiotherapy and diagnostic imaging has been investigated. Samples of phantom materials based on epoxy resin, polyethylene, a polystyrene-polypropylene mixture and commercially available phantom materials (Solid Water, Gammex RMI and Plastic Water, Nuclear Associates) were scanned at temperatures from 15 to 40 degrees C and HU values determined. At a reference temperature of 20 degrees C materials optimized for CT applications give HU values close to zero while the commercial materials show an offset of 119.77 HU (Plastic Water) and 27.69 HU (Solid Water). Temperature dependence was lowest for epoxy-based materials (EPX-W: -0.23 HU degrees C(-1); Solid Water: -0.25 HU degrees C(-1)) and highest for a polyethylene-based material (X0: -0.72 HU degrees C(-1)). A material based on a mixture of polystyrene and polypropylene (PSPPI: -0.27 HU degrees C(-1)) is comparable to epoxy-based materials and water (-0.29 HU degrees C(-1)).     

Water absorption characteristics of dental composites incorporating hydroxyapatite filler

Water uptake characteristics of BisGMA-based composites incorporating untreated and surface-treated hydroxyapatite (HA) with a silane coupling agent have been investigated. The water absorption and desorption behaviour of these composites obeyed the classical diffusion theory. The diffusion coefficients of the composites during first absorption were very similar to that for the base resin, suggesting that the water uptake process occur mainly in the resin matrix. The incorporation of HA reduced the water uptake of the base resin and lower uptake was found for those formulated with surface-treated HA. It was also observed that the equilibrium uptake decreased with increasing filler loading. However, the filled specimens had a higher water absorption than which would be expected on the basis of the resin content. This increase in the water uptake was largely due to the presence of porosity and filler particle aggregates in the microstructure of composites, although the adsorption of some water onto the filler surface has not been ruled out. The experimental composites showed higher solubilities than that obtained for the base resin.     

Transmission of water through a biocompatible polyurethane: application to circulatory assist devices

The permeability characteristics of a water-segmented polyurethane (Biomer) system under the conditions encountered in circulatory-assist devices were investigated. A diffusion cell and permeability system providing precise control of membrane boundary conditions and allowing continuous measurement of water vapor transmission was designed. Liquid water at 37 degrees C was used as the donor fluid and the system incorporated a constant-flow nitrogen carrier gas and an optical dew point sensor downstream to determine the water vapor mass flow rate as a function of time. The mass flow rate was then numerically integrated and plotted against time to allow calculation of effective diffusion coefficient (D) by the dynamic time lag method. Steady-state permeabilities were found to be insensitive to donor chamber hydrostatic pressure (50-200 mm Hg) indicating that bulk flow is not a transport mechanism in these membranes. The permeability coefficient (P) was independent of membrane thickness (H) over the four samples tested (0.0102, 0.0148, 0.0269, and 0.0366 cm), with an average value of 3.29 X 10(-4) cm2/s. Thus, diffusion was Fickian with negligible boundary layers. A plot of lag time versus H2 was linear (R = 0.98) yielding a value for D of 2.18 X 10(-7) cm2/s. A water-Biomer partition coefficient was determined for each sample with an average value of 1525, indicating a moderately hydrophilic membrane with a water sorption of 6.3% at 37 degrees C. Since water transport is by Fickian diffusion in the absence of bulk flow, liquid water cannot be expected to accumulate in circulatory-assist devices unless a condensing surface is maintained within the system.     

Trifunctional methacrylate monomers and their photocured composites with reduced curing shrinkage,water sorption,and water solubility

Novel trifunctional methacrylates, 1,1,1-tris[4-(2'-acetoxy-3'-methacryloyloxypropoxy)phenyl]ethane (Ac-THMPE) and 1,1,1-tris[4-(2'-acetoxy-3'-methacryloyloxypropoxy)phenyl]methane (Ac-THMPM), have been prepared by acetylation of the hydrophilic hydroxyl groups of 1,1,1-tris[4-(2'-hydroxy-3'-methacryloyloxypropoxy)phenyl]ethane (THMPE) and 1,1,1-tris[4-(2'-hydroxy-3'-methacryloyloxypropoxy)phenyl]methane (THMPM), respectively, for use as dental monomers. Decrease in monomer viscosity resulted from the acetylation. Unfilled resins and composites based on the four trimethacrylates were evaluated for photopolymerization conversion, water contact angle, and curing shrinkage. Water sorption, water solubility, and flexural strength of the composites prepared from the trimethacrylate were measured. Those data obtained for the trimethacrylate-containing materials were compared with control 2,2-bis[4-(2'-hydroxy-3'-methacryloyloxypropoxy)phenyl]propane (bis-GMA)-based materials in order to evaluate the applicability of the trimethacrylates as dental monomers. The acetylation of hydroxyl groups appeared to be an effective method to decrease curing shrinkage, water sorption, and water solubility of the dental composites. When compared with the bis-GMA composite, the composites based on Ac-THMPM and Ac-THMPM showed much lower curing shrinkage, water sorption, and water solubility, along with approximately equal conversion and flexural strength.     

Diffusivity of 125I-labelled macromolecules through collagen: mechanism of diffusion and effect of adsorption

Diffusion of angiotensin II, albumin and aldolase was studied through collagen membranes with swelling ratios between 4 and 15. The diffusion coefficient was measured from the time-lag for the onset of steady-state flux through the membrane. Binding of macromolecules to collagen was evaluated from the results of sorption studies conducted as a function of macromolecular concentration. Results presented indicate that the diffusion of macromolecules through collagen membrane is slowed by electrostatic and hydrogen bonding between individual macromolecular chains and collagen. The extent of adsorption is increased as the molecular weight of the diffusant increases. Diffusion of water soluble macromolecules through collagen occurs rapidly, suggesting that diffusion occurs through water filled channels as opposed to between collagen molecules. The results of these studies are useful in understanding diffusion through connective tissues and in the design of drug delivery systems based on collagen.