Correlation between age, location, orientation, loading velocity and delamination strength in the human aorta.

Aortic dissection is a biomechanical phenomenon associated with a failure of internal cohesion, which manifests itself through the delamination of the aortic wall. The goal of this study is to deepen our knowledge of the delamination strength of the aorta. To achieve this, 661 peeling experiments were carried out with strips of the human aorta collected from 46 cadavers. The samples were ordered into groups with respect to (1) anatomical location, (2) orientation of the sample, and (3) extension rate used within the experiment. The obtained results are in accordance with the hypothesis that delamination resistance is not sensitive to the extension rates 0.1, 1, 10, and 50 mms-1. We arrived at this conclusion for all positions along the aorta investigated in our study. These were the thoracic ascending (AAs), thoracic descending (ADs), and the abdominal aorta (AAb), simultaneously considering both the longitudinal (L) as well as the circumferential (C) orientations of the samples. On the other hand, our results showed that the delamination strength differs significantly with respect to the anatomical position and orientation of the sample. The medians of the delamination strength were as follows, 4.1 in AAs-L, 3.2 in AAs-C, 3.1 in ADs-L, 2.4 in ADs-C, AAb-L in 3.6, and 2.7 in AAb-C case (all values are in 0.01·Nmm-1). This suggests that resistance to crack propagation should be an anisotropic property and that the aorta is inhomogeneous along its length from the point of view of delamination resistance. Finally, correlation analysis proved that the delamination strength of the human aorta significantly decreases with age.

Vancomycin-Loaded Collagen/Hydroxyapatite Layers Electrospun on 3D Printed Titanium Implants Prevent Bone Destruction Associated with S. epidermidis Infection and Enhance Osseointegration.

The aim of the study was to develop an orthopedic implant coating in the form of vancomycin-loaded collagen/hydroxyapatite layers (COLHA+V) that combine the ability to prevent bone infection with the ability to promote enhanced osseointegration. The ability to prevent bone infection was investigated employing a rat model that simulated the clinically relevant implant-related introduction of bacterial contamination to the bone during a surgical procedure using a clinical isolate of Staphylococcus epidermidis. The ability to enhance osseointegration was investigated employing a model of a minipig with terminated growth. Six weeks following implantation, the infected rat femurs treated with the implants without vancomycin (COLHA+S. epidermidis) exhibited the obvious destruction of cortical bone as evinced via a cortical bone porosity of up to 20% greater than that of the infected rat femurs treated with the implants containing vancomycin (COLHA+V+S. epidermidis) (3%) and the non-infected rat femurs (COLHA+V) (2%). The alteration of the bone structure of the infected COLHA+S. epidermidis group was further demonstrated by a 3% decrease in the average Ca/P molar ratio of the bone mineral. Finally, the determination of the concentration of vancomycin released into the blood stream indicated a negligible systemic load. Six months following implantation in the pigs, the quantified ratio of new bone indicated an improvement in osseointegration, with a two-fold bone ingrowth on the COLHA (47%) and COLHA+V (52%) compared to the control implants without a COLHA layer (27%). Therefore, it can be concluded that COLHA+V layers are able to significantly prevent the destruction of bone structure related to bacterial infection with a minimal systemic load and, simultaneously, enhance the rate of osseointegration.

Rifampin-Releasing Triple-Layer Cross-Linked Fresh Water Fish Collagen Sponges as Wound Dressings.

OBJECTIVES: Surgical wounds resulting from biofilm-producing microorganisms represent a major healthcare problem that requires new and innovative treatment methods. Rifampin is one of a small number of antibiotics that is able to penetrate such biofilms, and its local administration has the potential to serve as an ideal surgical site infection protection and/or treatment agent. This paper presents two types (homogeneous and sandwich structured) of rifampin-releasing carbodiimide-cross-linked fresh water fish collagen wound dressings. METHODS: The dressings were prepared by means of the double-lyophilization method and sterilized via gamma irradiation so as to allow for testing in a form that is able to serve for direct clinical use. The mechanical properties were studied via the uniaxial tensile testing method. The in vivo rifampin-release properties were tested by means of a series of incubations in phosphate-buffered saline. The microbiological activity was tested against methicillin-resistant staphylococcus aureus (MRSA) employing disc diffusion tests, and the in vivo pharmacokinetics was tested using a rat model. A histological examination was conducted for the study of the biocompatibility of the dressings. RESULTS: The sandwich-structured dressing demonstrated better mechanical properties due to its exhibiting ability to bear a higher load than the homogeneous sponges, a property that was further improved via the addition of rifampin. The sponges retarded the release of rifampin in vitro, which translated into at least 22 hours of rifampin release in the rat model. This was significantly longer than was achieved via the administration of a subcutaneous rifampin solution. Microbiological activity was proven by the results of the disc diffusion tests. Both sponges exhibited excellent biocompatibility as the cells penetrated into the scaffold, and virtually no signs of local irritation were observed. CONCLUSIONS: We present a novel rifampin-releasing sandwich-structured fresh water fish collagen wound dressing that has the potential to serve as an ideal surgical site infection protection and/or treatment agent.

Surface Treatment of Acetabular Cups with a Direct Deposition of a Composite Nanostructured Layer Using a High Electrostatic Field.

A composite nanofibrous layer containing collagen and hydroxyapatite was deposited on selected surface areas of titanium acetabular cups. The layer was deposited on the irregular surface of these 3D objects using a specially developed electrospinning system designed to ensure the stability of the spinning process and to produce a layer approximately 100 micrometers thick with an adequate thickness uniformity. It was verified that the layer had the intended nanostructured morphology throughout its entire thickness and that the prepared layer sufficiently adhered to the smooth surface of the model titanium implants even after all the post-deposition sterilization and stabilization treatments were performed. The resulting layers had an average thickness of (110 ± 30) micrometers and an average fiber diameter of (170 ± 49) nanometers. They were produced using a relatively simple and cost-effective technology and yet they were verifiably biocompatible and structurally stable. Collagen- and hydroxyapatite-based composite nanostructured surface modifications represent promising surface treatment options for metal implants.

Effect of axial prestretch and adipose tissue on the inflation-extension behavior of the human abdominal aorta.

Our study aims to show that perivascular adipose tissue may significantly change the mechanical state of the abdominal aorta. To this end, uniaxial tensile tests with perivascular fat tissue were carried out. In the subsequent regression analysis, stress-strain data were fitted by the polynomial strain energy density. A constitutive model of adipose tissue was used in the analytical simulation of the inflation-extension behavior of the human abdominal aorta. The computational model was based on the theory of the bi-layered thick-walled tube. In addition to the effect of perivascular tissue, the effect of axial prestretch was also studied. It was found that the presence of perivascular tissue reduces the distensibility of the aorta. Axial prestretch applied to the aorta embedded in adipose tissue had an effect opposite to that of adipose tissue. Axially prestrained aorta exhibited higher distensiblity than non-prestrained aorta. It was also shown that the perivascular envelope bears some portion of the pressure loading and thus reduces the mechanical stresses inside the wall of aorta. A similar effect was found for axial prestretch.

Evaluation of collagen/hydroxyapatite electrospun layers loaded with vancomycin, gentamicin and their combination: Comparison of release kinetics, antimicrobial activity and cytocompatibility.

The aim of this study was to develop a biodegradable nanostructured electrospun layer based on collagen (COL), hydroxyapatite nanoparticles (HA), vancomycin hydrochloride (V), gentamicin sulphate (G) and their combination (VG) for the treatment of prosthetic joint infections and the prevention of infection during the joint replacement procedure. COL/HA layers containing different amounts of HA (0, 5 and 15 wt%) were tested for the in vitro release kinetics of antibiotics, antimicrobial activity against MRSA, gentamicin-resistant Staphylococcus epidermidis and Enterococcus faecalis isolates and cytocompatibility using SAOS-2 bone-like cells. The results revealed that the COL/HA layers released high concentrations of vancomycin and gentamicin for 21 days and performed effectively against the tested clinically-relevant bacterial isolates. The presence of HA in the collagen layers was found not to affect the release kinetics of the vancomycin from the layers loaded only with vancomycin or its combination with gentamicin. Conversely, the presence of HA slowed down the release of gentamicin from the COL/HA layers loaded with gentamicin and its combination with vancomycin. The combination of both antibiotics exerted a positive effect on the prolongation of the conversion of vancomycin into its degradation products. All the layers tested with different antibiotics exhibited potential antibacterial activity with respect to both the tested staphylococci isolates and enterococci. The complemental effect of vancomycin was determined against both gentamicin-resistant Staphylococcus epidermidis and Enterococcus faecalis in contrast to the application of gentamicin as a single agent. This combination was also found to be more effective against MRSA than is vancomycin as a single agent. Importantly, this combination of vancomycin and gentamicin in the COL/HA layers exhibited sufficient cytocompatibility to SAOS-2, which was independent of the HA content. Conversely, only gentamicin caused the death of SAOS-2 independently of HA content and only vancomycin stimulated SAOS-2 behaviour with an increased concentration of HA in the COL/HA layers. In conclusion, COL/HA layers with 15 wt% of HA impregnated with vancomycin or with a combination of vancomycin and gentamicin offer a promising treatment approach and the potential to prevent infection during the joint replacement procedures.

A human pericardium biopolymeric scaffold for autologous heart valve tissue engineering: cellular and extracellular matrix structure and biomechanical properties in comparison with a normal aortic heart valve.

The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p < 0.001) higher collagen I content, a lower collagen III and elastin content, and a similar glycosaminoglycans (GAGs) content, in comparison with the NAV, as measured by ECM integrated density. However, the relative thickness of the main load-bearing structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p < 0.05) than in the longitudinal direction. This proved that both tissues were anisotropic. No statistically significant differences in UTS (ultimate tensile strength) values and in calculated bending stiffness values in the longitudinal or transversal direction were found between HP and NAV. Our study confirms that HP has an advantageous ECM biopolymeric structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.

Fixation of distal fibular fractures: A biomechanical study of plate fixation techniques.

Ankle fractures are complex injuries with variable prognoses that depend upon many factors. The aim of the treatment is to restore the ankle joint biomechanical stability with maximum range of motion. Most ankle fractures are fibular fractures, which have a typical oblique fracture line in the distal fibula located in the area of the tibiofibular syndesmosis. The aim of this study was to simulate numerically several fixation techniques of the distal fibular fractures, evaluate their stability, determine their impact on surrounding tissue load, and correlate the results to clinical treatment experience. The following three models of fibular fracture fixation were used: (a) plate fixation with three screws attached above/below and lag screws, (b) plate fixation with two screws attached above/below and lag screws, and (c) three lag screws only. All three fracture fixation models were analyzed according to their use in both healthy physiological bone and osteoporotic bone tissue. Based on the results of Finite Element Analysis for these simulations, we found that the most appropriate fixation method for Weber-B1 fibular fractures was an unlocked plate fixation using six screws and lag screws, both in patients with physiological and osteoporotic bone tissue. Conversely, the least appropriate fixation method was an unlocked plate fixation with four screws and lag screws. Although this fixation method reduces the stress on patients during surgery, it greatly increased loading on the bone and, thus, the risk of fixation failure. The final fixation model with three lag screws only was found to be appropriate only for very limited indications.

The release kinetics, antimicrobial activity and cytocompatibility of differently prepared collagen/hydroxyapatite/vancomycin layers: Microstructure vs. nanostructure.

The aim of this study was to develop an osteo-inductive resorbable layer allowing the controlled elution of antibiotics to be used as a bone/implant bioactive interface particularly in the case of prosthetic joint infections, or as a preventative procedure with respect to primary joint replacement at a potentially infected site. An evaluation was performed of the vancomycin release kinetics, antimicrobial efficiency and cytocompatibility of collagen/hydroxyapatite layers containing vancomycin prepared employing different hydroxyapatite concentrations. Collagen layers with various levels of porosity and structure were prepared using three different methods: by means of the lyophilisation and electrospinning of dispersions with 0, 5 and 15wt% of hydroxyapatite and 10wt% of vancomycin, and by means of the electrospinning of dispersions with 0, 5 and 15wt% of hydroxyapatite followed by impregnation with 10wt% of vancomycin. The maximum concentration of the released active form of vancomycin characterised by means of HPLC was achieved via the vancomycin impregnation of the electrospun layers, whereas the lowest concentration was determined for those layers electrospun directly from a collagen solution containing vancomycin. Agar diffusion testing revealed that the electrospun impregnated layers exhibited the highest level of activity. It was determined that modification using hydroxyapatite exerts no strong effect on vancomycin evolution. All the tested samples exhibited sufficient cytocompatibility with no indication of cytotoxic effects using human osteoblastic cells in direct contact with the layers or in 24-hour infusions thereof. The results herein suggest that nano-structured collagen-hydroxyapatite layers impregnated with vancomycin following cross-linking provide suitable candidates for use as local drug delivery carriers.

A comparison of age-related changes in axial prestretch in human carotid arteries and in human abdominal aorta.

It is known that large arteries in situ are subjected to significant axial prestretch. This prestretch plays an important physiological role in optimizing the biomechanical response of an artery. It is also known that the prestretch declines with age. However, a detailed description of age-related changes in prestretch is available only for the abdominal aorta and for the femoropliteal artery. Our study presents results of measurements of axial prestretch in 229 left common carotid arteries excised in autopsies. It was found that the prestretch of the carotid artery correlates significantly with age ([Formula: see text], p value < 0.001). A linear regression model was used to fit the observations. Simultaneously with the measurement of the prestretch in the carotid artery, the axial prestretch was also measured in abdominal aorta. By comparing data obtained from these locations, it was concluded that the axial prestretch in the carotid artery is greater than in the abdominal aorta, and that atherosclerosis develops more rapidly in the abdominal aorta than in the carotid artery. Histological sections obtained from 8 carotid arteries and aortas suggest that the medial layer of the left common carotid artery is significantly thinner than aortic media (median/IQR: 0.343/0.086 vs. 0.482/0.172 mm, [Formula: see text] in Wilcoxon signed-rank test) and simultaneously that carotid media contains a lower number of elastic membranes (median/IQR: 26.5/11.8 vs. 31.5/11.8, [Formula: see text] in the Wilcoxon signed-rank test). This could be a reason for the different extent of the prestretch observed in aorta and in carotid artery. Our data sample also contains 5 measurements of the axial prestretch in abdominal aortas suffering from an aneurysm. It was found that aneurysmatic aortas also exhibit axial retraction when excised from in situ position. To the best of our knowledge, this is the first time that detailed data characterizing axial prestretch of the human left common carotid artery have been presented.

The Sustainable Release of Vancomycin and Its Degradation Products From Nanostructured Collagen/Hydroxyapatite Composite Layers.

Infections of the musculoskeletal system present a serious problem with regard to the field of orthopedic and trauma medicine. The aim of the experiment described in this study was to develop a resorbable nanostructured composite layer with the controlled elution of antibiotics. The layer is composed of collagen, hydroxyapatite nanoparticles, and vancomycin hydrochloride (10 wt%). The stability of the collagen was enhanced by means of cross-linking. Four cross-linking agents were studied, namely an ethanol solution, a phosphate buffer solution of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide, genipin, and nordihydroguaiaretic acid. High performance liquid chromatography was used so as to characterize the in vitro release rates of the vancomycin and its crystalline degradation antibiotically inactive products over a 21-day period. The maximum concentration of the released active form of vancomycin (approximately 265 mg/L) exceeded the minimum inhibitory concentration up to an order of 17 times without triggering the burst releasing effect. At the end of the experiment, the minimum inhibitory concentration was exceeded by up to 6 times (approximately 100 mg/L). It was determined that the modification of collagen with hydroxyapatite nanoparticles does not negatively influence the sustainable release of vancomycin. The balance of vancomycin and its degradation products was observed after 14 days of incubation.

Limiting extensibility constitutive model with distributed fibre orientations and ageing of abdominal aorta.

The abdominal aorta is susceptible to age-related pathological changes (arteriosclerosis, atherosclerosis, aneurysm, and tortuosity). Computational biomechanics and mechanobiology provide models capable of predicting mutual interactions between a changing mechanical environment and patho-physiological processes in ageing. However, a key factor is a constitutive equation which should reflect the internal tissue architecture. Our study investigates three microstructurally-motivated invariant-based hyperelastic anisotropic models suitable for description of the passive mechanical behaviour of the human abdominal aorta at a multiaxial state of stress known from recent literature. The three adopted models have also been supplemented with a newly proposed constitutive model (limiting extensibility with fibre dispersion). All models additively decouple the mechanical response of the isotropic (elastin and smooth muscle cells represented by the neo-Hookean term) and the anisotropic (collagen) parts. Two models use exponential functions to capture large strain stiffening ascribed to the engagement of collagen fibres into the load-bearing process. The other two models are based on the concept of limiting extensibility. Perfect alignment of reinforcing fibres with two preferred directions as well as fibre dispersion are considered. Constitutive models are calibrated to the inflation-extension response adopted from the literature based on the computational model of the residually-stressed thick-walled tube. A correlation analysis of determined material parameters was performed to reveal dependence on the age. The results of the nonlinear regression suggest that limiting fibre extensibility is the concept which is suitable to be used for the constitutive description of the aorta at multiaxial stress states and is highly sensitive to ageing-induced changes in mechanical response.

Analysis of axial prestretch in the abdominal aorta with reference to post mortem interval and degree of atherosclerosis.

It is a well-known fact that the length of an artery in situ and the length of an excised artery differs. Retraction of blood vessels is usually observed. This prestretch plays an important role in arterial physiology. We have recently determined that the decrease of axial prestretch in the human abdominal aorta is so closely correlated with age that it is suitable for forensic applications (estimation of the age at time of death for cadavers of unknown identity). Since post mortem autolysis may affect the reliability of an estimate based on axial prestretch, the present study aims to detail analysis of the effect of post mortem time. The abdominal aorta is a prominent site of atherosclerotic changes (ATH), which may potentially affect longitudinal prestretch. Thus ATH was also involved in the analysis. Axial prestretch in the human abdominal aorta, post mortem interval (PMI), and the degree of ATH were documented in 365 regular autopsies. The data was first age adjusted to remove any supposed correlation with age. After the age adjustment of the sample, the correlation analysis showed no significant PMI effects on the prestretch in non-putrefied bodies. Analysis of the prestretch variance with respect to ATH suggested that ATH is not a suitable factor to explain the prestretch variability remaining after the age adjustment. It was concluded that, although atherosclerotic plaques may certainly change the biomechanics of arteries, they do not significantly affect the longitudinal prestretch in the human abdominal aorta.

Axial prestretch and circumferential distensibility in biomechanics of abdominal aorta.

Elastic arteries are significantly prestretched in an axial direction. This property minimises axial deformations during pressure cycle. Ageing-induced changes in arterial biomechanics, among others, are manifested via a marked decrease in the prestretch. Although this fact is well known, little attention has been paid to the effect of decreased prestretch on mechanical response. Our study presents the results of an analytical simulation of the inflation-extension behaviour of the human abdominal aorta treated as nonlinear, anisotropic, prestrained thin-walled as well as thick-walled tube with closed ends. The constitutive parameters and geometries for 17 aortas adopted from the literature were supplemented with initial axial prestretches obtained from the statistics of 365 autopsy measurements. For each aorta, the inflation-extension response was calculated three times, with the expected value of the initial prestretch and with the upper and lower confidence limit of the initial prestretch derived from the statistics. This approach enabled age-related trends to be evaluated bearing in mind the uncertainty in the prestretch. Despite significantly decreased longitudinal prestretch with age, the biomechanical response of human abdominal aorta changes substantially depending on the initial axial stretch was used. In particular, substituting the upper limit of initial prestretch gave mechanical responses which can be characterised by (1) low variation in axial stretch and (2) high circumferential distensibility during pressurisation, in contrast to the responses obtained for their weakly prestretched counterparts. The simulation also suggested the significant effect of the axial prestretch on the variation of axial stress in the pressure cycle. Finally, the obtained results are in accordance with the hypothesis that circumferential-to-axial stiffness ratio is the quantity relatively constant within this cycle.

Age-related distribution of longitudinal pre-strain in abdominal aorta with emphasis on forensic application.

It is a well-known fact that the length of an artery in situ and the length of an excised artery differs. Retraction of blood vessels is usually observed. This pre-tension plays crucial role in arterial biomechanics. It augments an artery wall load-bearing capacity. This paper presents the longitudinal pre-strain of the human aorta as an index of human age. The length of abdominal aortas was measured during autopsies before and after segment resection. The longitudinal pre-strain was calculated in 130 donors; 100 male and 30 female bodies. The pre-strain was defined as the ratio between in situ length and the length after the excision. The mean pre-strain was found to be 1.18±0.10 for male and 1.14±0.10 for female sample (mean±standard deviation). The age in the male group was 41.6±15.9 years; and 47.7±17.7 years in the female group. Statistical analysis revealed the correlation coefficient between age and pre-strain r=-0.821 and r=-0.839 in male and female group, respectively. The analysis also confirmed close correlation between aortic circumference and age; and between circumference and pre-strain. Linear and power law regression equations were employed and prediction intervals were computed. The power law estimates the age more accurately than linear one model. Nevertheless, especially for small values of the pre-strain (aged individuals) the linear model can be advantageous.

Age estimation based on a combined arteriosclerotic index.

This study introduces a new quantity, the combined arteriosclerotic index (CAI), which is defined as the ratio between the diameter and the longitudinal prestrain of an artery. The longitudinal prestrain has been adopted as the ratio between the in situ length and the excised length of the abdominal aorta, and is a measure of arterial elasticity. During ageing, arteriosclerosis is manifested by the loss of pretension and by enlargement of the diameter of the artery. CAI combines these two effects. A sample of 61 female and 194 male autopsy measurements of human abdominal aortas shows that CAI correlates significantly with chronological age (R = 0.916/0.921; female/male). The sample had the following parameters: age 53 ± 19/48 ± 16 years; diameter of the abdominal aorta 12.4 ± 2.2/13.4 ± 2.1 mm; and longitudinal prestrain 1.13 ± 0.10/1.15 ± 0.10 (mean ± sample standard deviation; female/male). The resulting CAI was 11.2 ± 2.7/11.9 ± 2.6 mm. The classical linear regression model was employed for age estimation by CAI. The model gave a residual standard deviation of 7.6/6.3 years and a 95% prediction interval range of ± 15.4/12.5 years (female/male). A two-sample t-test confirmed that there are significant differences between the female and male population during ageing, reflected by CAI, unlike longitudinal prestrain. It was concluded that CAI is a suitable predictor of age at time of death and is easily obtainable in the autopsy room.

Correlations between age, prestrain, diameter and atherosclerosis in the male abdominal aorta.

The longitudinal prestrain of arteries facilitates their physiological function. Remodeling, adaptation and aging result in an age-dependent magnitude of the pretension. Although the phenomenon is known, detailed statistics, especially for human arteries, are lacking. This study was designed to propose the regression model capable of estimating the prestrain of the human abdominal aorta. The length of the abdominal aorta before, l, and after excision from the body, L, the diameter, heart weight, thickness of left ventricle and degree of atherosclerosis were collected in autopsies of 156 male cadavers of known age. Longitudinal prestrain was quantified by means of the stretch ratio λ=l/L. Statistical analysis revealed significant dependence between age, prestrain, diameter and atherosclerosis, which were best fitted to the power law equation. Longitudinal prestretch reduced with age significantly; λmean=1.30±0.07 for age<30 (n=29), whereas λmean=1.06±0.03 for age>59 (n=31) with p-value<0.0001. Raw data gave linear correlation coefficients as follows: λ-age (R=-0.842); l-age (R=0.023); L-age (R=0.476); (l-L)-age (R=-0.811). It was concluded that longitudinal prestrain decreases nonlinearly with age and both age and diameter are suitable predictors of the prestrain. Data suggests that unloaded length elongates with age in contrast to the elastic retraction.

Age related constitutive laws and stress distribution in human main coronary arteries with reference to residual strain.

An analytical model has been used to simulate the effects of tissue aging on residual strain, constitutive relations and stiffness parameter in the main right and left (ramus circumflexus) human coronary arteries, based on experimental data. The experimental opening angle theta scatters considerably with age. The optimum angle theta(op) approximately equals 70 degrees, which makes the circumferential stress uniform in the arterial wall at a normal blood pressure, is approximately constant throughout aging. Above age of the 15 years the estimated and experimental values of theta are greater than theta(op) and therefore the mechanical load of the inner layers of the media and the intima decreases and the adventitia is overloaded. On the basis of nonlinear regression analysis, age-related constitutive laws of arterial wall circumferential stiffness have been determined. Above the age of 30, arterial wall hardening increases rapidly. The left coronary artery is stiffer than the right artery for groups from 35 to 45 years of age. Hyperelasticity theory has been used to identify age-related multiaxial stress through wall thickness. A theoretical model based on the reduced Green strain provides a very good representation of the coronary artery circumferential mechanical response and predicts its nearly isotropic behavior. Bio-composite material forms non-homogeneous stresses and, in the course of aging, it increases the adventitia loading. In groups aged from 10 to 15 years, whose coronary artery residual strains are low, the circumferential stress distribution has a classic form. Stiffness parameter beta gradually increases with age and this increase is significant above the age of 60. Parameter beta tends to decrease when the opening angle theta increases.