**3. Classification of vascular access**

Aubaniac [18], in 1952, described the puncture of subclavian vein as a VA, while, in the 1960s, Dillard, Quinton, and Scribner [19], based on Alwall's experience, developed arteriovenous Teflon shunt inserted into radial artery and cephalic vein. Flexible silicon rubber replaced later Teflon. Based on Seldinger's technique, Shaldon inserted catheters into femoral artery and vein for dialysis sessions in 1961 [20, 21]. Vessels in different sites were used, over time, including

Cimino and Brescia [22] described, in 1962, a "simple venipuncture for hemodialysis." Fogarty et al. [23] invented, in 1963, a special designed catheter for thrombectomy and embolectomy with an inflatable balloon at its distal tip. In 1965, the first AVF was created, and 14 more in 1966 when Brescia, Cimino, Appel, and Hurwich published their paper [24]. Sperling [25], in 1967, created an end-to-end anastomosis in the forearm, between radial artery and cephalic vein, in 15 patients, whereas Appell did side-to-side anastomosis. End-to-end anastomosis usually is not the first choice of AVF due to high risk of steal syndrome in aging, diabetic patients of dialysis, but it remains a useful option in revision procedures, although it is

Nowadays, artery side-to-vein anastomosis seems to be a standard procedure [27], which began from Rohl et al. [28] in 1968. Girardet et al. [29] and Brittinger et al. [30] in 1970 described their experience with AVG between femoral vein and artery and subcutaneously fixed superficial femoral artery for chronic HD. Brittinger et al. [31] were the first to implant a plastic valve as a vascular access in an animal model, but unfortunately, their efforts did not proceed to a human one. In the early 1970s, Buselmeier et al. [32] developed a U-shaped silastic prosthetic AV shunt with either one or two Teflon plugged outlets, which communicated to the outside of the body. The U-shaped portion could be totally or partially implanted subcu‐ taneously. Subsequently, pediatric hemodialysis patients were extremely favored by this procedure. In 1976, Baker [33] presented expanded PTFE grafts in 72 hemodialysis patients. In the subsequent years, several publications indicated the benefits and the shortcomings of the prosthetic material in question, remaining the primary choice of graft for hemodialysis VA to date. The same year, two authors, Mindich and Dardik, had worked with a new graft material: the human umbilical cord vein [34, 35]. Regrettably so, this material did not succeed in becoming a revolutionary graft material due to its inadequate resistance against the trauma of repeated cannulations and their complications (aneurysm and infection). After the subcla‐ vian route for hemodialysis access was firstly introduced by Shaldon in 1961, it was further processed in 1969 by Josef Erben, using the intraclavicular route [36]. In the next 20 years or so, the subclavian vein was the preferred access for temporary vascular access by central venous catheterization. Today, due to phlebographic studies revealing a 50% stenosis or occlusion rate at the cannulation site, subclavian route has been discarded. Subclavian stenosis and occlusion predispose to edema of the arm, especially after creation of an AV fistula [37]. The first angioplasty described by Dotter et al. [38], who introduced a type of balloon, was immensely conducive to the resolution of one of the most significant predicaments in vascular

In 1977, Gracz et al. [39] created the "proximal forearm fistula for maintenance hemodialysis," a variant of an AV anastomosis. An adjustment of this AVF became quite significant in the old,

the subclavian, jugular, and femoral vein.

246 Updates in Hemodialysis

surgery and vascular access surgery.

correlated with higher mortality risk from infections [26].

Nowadays, and thanks to all above efforts, nephrologists have the ability to choose the most suitable VA for their patients depending on special needs of each one. Based on expected halflife, the first demarcation is of permanent and temporary VAs [43]. Long-term or permanent VAs are called the ones with an expected half-life of more than 3 years, and mainly include AVF [13] and PTFE AVG. VAs with expected half-life of less than 90 days are called temporary VAs and basically are noncuffed double lumen catheters and arteriovenous shunts. The VAs with half-life between the above categories (90 days to 3 years) are the mid-term VA containing tunneled cuffed catheters, port devices and external and internal shunts.

#### **3.1. Acute hemodialysis vascular access**

Acute hemodialysis is a lifesaving treatment, which needs a VA in order to be carried out. When a permanent VA is not available, the preferred and currently available VA for acute hemodialysis is cuffed tunneled and noncuffed nontunneled hemodialysis catheters (Figures 1–5). The reason is that they can be used immediately and placed relatively easily. For catheter insertion, a modified Seldinger guide wire technique is used, preferably with ultrasound guided assistance for minimizing acute placement complications [44, 45].

**Figure 1.** Noncuffed in jugular double lumen catheter.

**Figure 2.** Cuffed tunneled in jugular double lumen catheter.

**Figure 3.** Permanent cuffed jugular catheter.

**Figure 4.** Acute noncuffed jugular catheter.

**Figure 5.** Femoral noncuffed catheter.

**Figure 2.** Cuffed tunneled in jugular double lumen catheter.

248 Updates in Hemodialysis

**Figure 3.** Permanent cuffed jugular catheter.

**Figure 4.** Acute noncuffed jugular catheter.

The most used and feasible are the noncuffed nontunneled catheters with easy insertion and availability for immediate use. They have some specific technical characteristics; they are made of polymers inelastic at room temperature, facilitating the insertion, but unstiffening at inner body temperature in order to be atraumatic for the vessels. The distance between the inflow and the outflow tip of the catheter must be at least 2 cm to lessen recirculation [46].

Central veins such as jugular or femoral can be used as insertion routes of these catheters [47]. Subclavian typically is an option, but due to its higher incidence of complications, such us lung injury, it is used when the others insertion sites are not feasible.

The National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) 2006 guidelines recommend the radiographical identification of tip placement and any potential complications before catheter use or anticoagulation treatment [48]. Subclavian vein should be avoided for catheter insertion due to high frequency of stenosis and thrombosis.

There are restrictions concerning the use of these catheters such as the blood flow with a maximum pump speed of 300 ml/min, although actual blood flow tops at 250 ml/min, catheters for insertion in femoral vein should be no less of 18 to 25 cm long to minimize recirculation [49, 50]. Their insertion site determines their life use, with the ones in internal jugular vein be suitable for use for about 2 to 3 weeks, while in femoral vein are used for 3 to 7 days in bedridden patients and for a single treatment in ambulatory patients [51]. Nevertheless, according to KDOQI guidelines, the life use of noncuffed, nontunneled catheters must be of a week or less; when hemodialysis treatment will be required for a longer period, the placement of cuffed, tunneled catheters is suggested [48]. Especially in hospitalized patients, triple lumen catheters are placed, using the third lumen for intravenous drugs and fluid administration and for blood drawing. It seems that two and three lumen catheters have similar blood flow and inflections incidence [52]. The leader cause for catheter removal is infectious complications.

#### **3.2. Permanent vascular access**

Taking patient-dependent factors into consideration, such as life expectancy, comorbidities, the status of the venous and arterial vascular system, is very important in order to prescribe the appropriate access. Each type of access, such as arteriovenous fistula (AVF), arteriovenous graft (AVG) or TC, has a different effect on circulatory system, and this should be taken into consideration. Also, the duration of their functionality and the risk for infection and thrombosis are important factors to consider. Each type of surgical anastomosis has advantages and disadvantages [53]. Also, it seems that the advantages of an AVF attempt strategy lessened considerably among older patients, particularly women with diabetes, reflecting the effect of lower AVF success rate and lower life expectancy, suggesting that vascular access-related outcomes may be optimized by considering individual patient characteristics [54]. The American Association for Vascular Surgery and the Society for Vascular Surgery, in 2002, for better consultation and understanding between physicians and registration of VA set VA reporting standards in which three components should be listed, structure (autogenous, prosthetic), position and alignment (loop, direct, etc.) [55]. Risk factors such as female gender, age, diabetic nephropathy, dialysis initiation via CVC and inability of VA maturation before HD initiation are responsible for the majority of VA failure. Repetitive VA failures are risk factor for mortality [56]. It seems that early referral to nephrologist and patient's education leads to initiation of dialysis with permanent VA, better metabolic and clinical situation, lower long-term morbidity and higher 2-year survival [57–61]. It is of benefit to the patient to begin hemodialysis treatment via a functional AVF than with a TC [62–64]; however, grafts are a better alternative to TCs, when AVF is not feasible [65]. Patients with bilateral central vein stenosis often require more than one vascular access modality to achieve a "personal access solution." Native long saphenous vein loops provided the best long-term patency. Expedited renal transplantation with priority local allocation of cadaveric organs to patients with precarious vascular access provides a potential solution [66]. Patients who received either femoral AVG or HeRO VA device experience poor access patency. ESRD patients who receive either of these procedures appear to be at the end stage of available access options [67].

#### *3.2.1. Arteriovenous fistula*

The first choice of VA is AVF, for its longevity and low morbidity and mortality rates [68, 69], low complication incidence for infection (one-tenth of AVGs) and thrombosis (one-sixth of AVGs) [70, 71]. AVFs' primary patency rates at 1 year vary considerably between USA and Europe, with reports from the USA that include diabetic patients be as low as 40–43% [72, 73]. From the study of 748 AVFs in diabetic patients over 5 years, Konner et al. showed a primary patency rate of 69–81% [74], while Chemla et al. had a rate of 80% at 22 months in 552 radio‐ cephalic AVFs in 153 patients over a 4-year period [75]. Hemodialysis patients with AVF have lower mortality and that seems to be attributed not only to decreased incidence of infections and VA dysfunctions but also to other factors, such as LVEF increase and blood pressure and arterial stiffness reduction, as Korsheed et al. [76] showed.

Based on the way of their creation, three types of AVFs can be identified. The first type belongs to the AVFs where an artery and a vein are connected in their natural position, with a side-toside or side-artery-to-vein-end anastomosis. In the second type, a vein is connected to an artery in end-to-side form, after its metathesis, to connect a further distance or surface the vein to facilitate cannulation; a tunnel creation is required for vein's new positioning. When a vein is connected to an artery end-to-end after it is removed from its anatomical location, we have the third type of AVF [77] (Figures 6–9). The end-to-end technique is abandoned nowadays since it leads to advanced risk for ischemia and thrombosis. Vein end to artery side anastomosis is the most common technique. The first option for the primary AVF is the radial-cephalic. Distal forearm ulnar-basilic has similar secondary patency rate to it and is the best alternative when the first one is not feasible [78]. Stenosis due to technical problems like false surgical cut of vein leads to dysfunctional VA. Complications such as heart failure or steal syndrome may result from a more proximal, big arterial anastomosis [77]. Local anesthesia is usually effective for AVF creation, and the morbidity of the procedure is low. AVF requires time after its creation for maturation before cannulation for at least 14 days according to DOPPS (Data from the Dialysis Outcomes and Practice Patterns Study). During the period of maturation, the blood flow and the vessel size increase over time in 8–12 weeks, and the initial blood flow is in a range of 200–300 ml/min [64].

**Figure 6.** Forearm AVF.

**3.2. Permanent vascular access**

250 Updates in Hemodialysis

*3.2.1. Arteriovenous fistula*

Taking patient-dependent factors into consideration, such as life expectancy, comorbidities, the status of the venous and arterial vascular system, is very important in order to prescribe the appropriate access. Each type of access, such as arteriovenous fistula (AVF), arteriovenous graft (AVG) or TC, has a different effect on circulatory system, and this should be taken into consideration. Also, the duration of their functionality and the risk for infection and thrombosis are important factors to consider. Each type of surgical anastomosis has advantages and disadvantages [53]. Also, it seems that the advantages of an AVF attempt strategy lessened considerably among older patients, particularly women with diabetes, reflecting the effect of lower AVF success rate and lower life expectancy, suggesting that vascular access-related outcomes may be optimized by considering individual patient characteristics [54]. The American Association for Vascular Surgery and the Society for Vascular Surgery, in 2002, for better consultation and understanding between physicians and registration of VA set VA reporting standards in which three components should be listed, structure (autogenous, prosthetic), position and alignment (loop, direct, etc.) [55]. Risk factors such as female gender, age, diabetic nephropathy, dialysis initiation via CVC and inability of VA maturation before HD initiation are responsible for the majority of VA failure. Repetitive VA failures are risk factor for mortality [56]. It seems that early referral to nephrologist and patient's education leads to initiation of dialysis with permanent VA, better metabolic and clinical situation, lower long-term morbidity and higher 2-year survival [57–61]. It is of benefit to the patient to begin hemodialysis treatment via a functional AVF than with a TC [62–64]; however, grafts are a better alternative to TCs, when AVF is not feasible [65]. Patients with bilateral central vein stenosis often require more than one vascular access modality to achieve a "personal access solution." Native long saphenous vein loops provided the best long-term patency. Expedited renal transplantation with priority local allocation of cadaveric organs to patients with precarious vascular access provides a potential solution [66]. Patients who received either femoral AVG or HeRO VA device experience poor access patency. ESRD patients who receive either of these procedures appear to be at the end stage of available access options [67].

The first choice of VA is AVF, for its longevity and low morbidity and mortality rates [68, 69], low complication incidence for infection (one-tenth of AVGs) and thrombosis (one-sixth of AVGs) [70, 71]. AVFs' primary patency rates at 1 year vary considerably between USA and Europe, with reports from the USA that include diabetic patients be as low as 40–43% [72, 73]. From the study of 748 AVFs in diabetic patients over 5 years, Konner et al. showed a primary patency rate of 69–81% [74], while Chemla et al. had a rate of 80% at 22 months in 552 radio‐ cephalic AVFs in 153 patients over a 4-year period [75]. Hemodialysis patients with AVF have lower mortality and that seems to be attributed not only to decreased incidence of infections and VA dysfunctions but also to other factors, such as LVEF increase and blood pressure and

Based on the way of their creation, three types of AVFs can be identified. The first type belongs to the AVFs where an artery and a vein are connected in their natural position, with a side-to-

arterial stiffness reduction, as Korsheed et al. [76] showed.

**Figure 7.** Side-to-side forearm AVF.

The placement of AVFs should be initiated when the patient reaches CKD stage 4, or within 1 year of the anticipated start of dialysis. In their recent study, Hod et al. [79] suggested that

**Figure 8.** End-to-end forearm AVF.

**Figure 9.** Side-to-end forearm AVF.

creating AVF more than 6 to 9 months before initiating dialysis in elderly may not associate with better AVF success rate. In order to increase the possibilities of a well-functioning AVF's creation and to minimize the complication, a physical examination must be done prior to procedure to identify any differences in blood pressure between the upper extremities [80] and the presence or lack of a well-developed palmar arch to avoid steal syndrome in case of using the dominant artery for AVF creation [81].

Additional information before the creation of AVF can be given with ultrasound of the vessels; their diameter is closely correlated with surgery success with a size of 2 mm and more leads with fruitful maturation [80], in contrast of a size of 1.6 mm and less, which predispose to failure [82]. The upper extremity AVF is the preferred access for hemodialysis, the duplex ultrasound identifies suitable arteries and veins for its successful creation, while early detection and intervention can save the fistula when complications occur [83]. Uzun et al. [84] showed that autologous saphenous vein can be preferably chosen as a prosthetic hemodialysis access graft due to its higher primary and secondary patency and lower complication rate and cost when compared with PTFE grafts. According to the vascular access guidelines of KDOQI, a well-functioning AVF has blood flow over 600 ml/min, with a diameter greater than 6 mm, and is lying less than 6 mm from the surface in a depth between 5 and 10 mm. When an AVF's maturation progresses successfully, then rapidly after surgery blood flow increases from baseline values of 30 to 50 ml/min, reaching 200 to 800 ml/min within 1 week; after 8 weeks, blood flow is over 480 ml/min [85, 86]. The AVFs must be evaluated 4–6 weeks after placement; experienced examiners (e.g., dialysis nurses) can identify nonmaturing fistulas with 80% accuracy [87]. Patients with newly placed AVF are advised for hand squeezing exercises to increase the rate of fistula maturation, such as squeezing a ball, bicep curls, and finger tips touches resulting to fistulae dilation [88, 89]. Far Infrared therapy, which is a form of heat therapy, has been implicated in improvement of endothelial function and hemodynamics in coronary arteries, probably through up-regulating endothelial nitric oxide synthase (eNOS) expression in arterial endothelium, leading to improved cardiac function in patients with chronic heart diseases. Repeated leg hyperthermia using FIR has been shown to reduce oxidative stress in bed-ridden type II diabetics and may positively influence the complex process of AVF maturation, improving both primary and secondary patency rates [90, 91]. Jennings et al. [92] published a trial, which showed that Venous Window Needle Guide, a subcutaneously placed hemodialysis cannulation device, is safe and effective in facilitating AVF cannulation for patients with an otherwise mature but noncannulatable access. Strozecki et al. described a case report of a 65-year-old female patient who had several hemodialysis sessions by cannulation of dilated collateral abdominal veins with dialysis needles, as an unconventional vascular access for HD in case of central vein occlusion [93]. Humerobasilic and radiocephalic AVF are the two VA types with the most functioning longevity, although in radiocephalic AVF, there is high initial failure rate [94]. It is the preferable VA due to its longevity, low incidence of complications, and easy cannulation [95–97]. In case of failure of radiocephalic AVF creation, the second most preferable VA is brachiocephalic AVF, which comes first in diabetic patients, in whom the inadequacy of vessels for radiocephalic AVF is usually found [98] with a reported 4-year patency of 80% [99]. According to a study of Rondriguez et al., brachiocephalic AVF has a lower survival than radiocephalic. Four years after its creation, just over 50% of the patients have patent AVF and about 30% after 8 years. Failure at first VA increases the risk for following failure, while successful development of the first VA, at about 60% of patients, does not lead to subsequent failure. Diabetes and female gender seem to be risk factors to VA failure [94].

#### *3.2.2. Arteriovenous graft*

creating AVF more than 6 to 9 months before initiating dialysis in elderly may not associate with better AVF success rate. In order to increase the possibilities of a well-functioning AVF's creation and to minimize the complication, a physical examination must be done prior to procedure to identify any differences in blood pressure between the upper extremities [80] and the presence or lack of a well-developed palmar arch to avoid steal syndrome in case of using

Additional information before the creation of AVF can be given with ultrasound of the vessels; their diameter is closely correlated with surgery success with a size of 2 mm and more leads with fruitful maturation [80], in contrast of a size of 1.6 mm and less, which predispose to failure [82]. The upper extremity AVF is the preferred access for hemodialysis, the duplex ultrasound identifies suitable arteries and veins for its successful creation, while early detection and intervention can save the fistula when complications occur [83]. Uzun et al. [84] showed that autologous saphenous vein can be preferably chosen as a prosthetic hemodialysis access graft due to its higher primary and secondary patency and lower complication rate and cost when compared with PTFE grafts. According to the vascular access guidelines of KDOQI, a well-functioning AVF has blood flow over 600 ml/min, with a diameter greater than 6 mm, and is lying less than 6 mm from the surface in a depth between 5 and 10 mm. When an AVF's maturation progresses successfully, then rapidly after surgery blood flow increases from baseline values of 30 to 50 ml/min, reaching 200 to 800 ml/min within 1 week; after 8 weeks, blood flow is over 480 ml/min [85, 86]. The AVFs must be evaluated 4–6 weeks after placement; experienced examiners (e.g., dialysis nurses) can identify nonmaturing fistulas with 80% accuracy [87]. Patients with newly placed AVF are advised for hand squeezing exercises to increase the rate of fistula maturation, such as squeezing a ball, bicep curls, and finger tips

the dominant artery for AVF creation [81].

**Figure 8.** End-to-end forearm AVF.

252 Updates in Hemodialysis

**Figure 9.** Side-to-end forearm AVF.

In the USA, AVGs (Figures 10–12) are the most common type of VA that is used for hemo‐ dialysis [100]. However, they last less than AVFs and have more complications such as infections and thromboses [70]. Recent technological advances using tissue-engineered AVGs have shown promise for patients receiving hemodialysis and their potential to provide an attractive, viable option for vascular access [101]. Grafts present a second choice of VA when AVF is not possible to be performed because of vascular problems [102]. AVGs have lower risk of nonmaturation in lower time [103]. They can be placed in the forearm, the upper arm and the thigh, when upper-extremity options are exhausted [104] and they can have a straight, curved or loop configuration. Axillary loop arm graft yields acceptable early patency rates in specific patients with vascular problems [105]. Another advantage is that AVGs may offer a large surface for cannulation. Some types of AVGs such as PTFE AVGs can be cannulated immediately after their placement, according to some studies, although it is preferable to wait for about 2 to 3 weeks for the first cannulation [106, 107]. However, the usual time for a functional graft is 2 to 3 weeks in order to reduce the post surgical edema and the perigraft hematoma and seroma [108]. Karatepe et al. [109] presented a novel polycarbonate urethane nanofabric graft, produced by electrospinning technology, which had self-healing features that avoid seroma formation and allow puncturing within 48 hours. It had good 12-month primary and secondary patency rates and substantially lowers infection rates. Early experience with GORE Acuseal is encouraging with patency and bacteremia rates at least comparable to standard polytetrafluoroethylene grafts, permitting cannulation within 24 hours of insertions and line avoidance in the majority of patients [110].

**Figure 10.** Upper arm AVG.

**Figure 11.** Looped forearm AVG.

**Figure 12.** Straight femoral AVG.

### *3.2.3. Tunneled hemodialysis catheter*

and secondary patency rates and substantially lowers infection rates. Early experience with GORE Acuseal is encouraging with patency and bacteremia rates at least comparable to standard polytetrafluoroethylene grafts, permitting cannulation within 24 hours of insertions

and line avoidance in the majority of patients [110].

**Figure 10.** Upper arm AVG.

254 Updates in Hemodialysis

**Figure 11.** Looped forearm AVG.

**Figure 12.** Straight femoral AVG.

TCs (Figures 2 and 3) have higher mortality risk than AVFs or AVGs; thus, they are used when the creation of the latter is not feasible [111]. There are several reasons that lead to the inability for AVF or AVG creation, such as multiple vascular surgeries, which lead to vascular thrombosis, or when patients have severe peripheral vascular disease or very low cardiac output. TCs are more frequently encountered in pediatric and very old patients. They can also be used as a bridge until AVF or AVG maturation [111]. Their use remains very high during the first year of HD care and is associated with high mechanical and infection rates [112]. The incidence of AVFs has been effectively increased since the "fistula first" has been developed [113], although it is accompanied with an increase in TCs, especially those used as a bridge until the maturation of an AVF [100]. Nonetheless, DOPPS shows an increasing use of TCs for the period 1996 to 2006 in many countries [114], which is in accordance with our data of 2011, which showed increased prevalence of TCs in female hemodialysis patients [115]. It is also signified that it is more likely for a patient to have permanent VA (AVF or AVG) than TC if he is at a center with experienced vascular surgery department successfully creating permanent VA in diabetic, older women and early AVF cannulation practice (within 4 weeks from its formation) [114].

They do not last as much as the others types of VA, and they have higher complication rates such as infections. There are studies revealing that CVCs are colonized within the first 10 days of placement; however, the catheter's lumen colonization does not equal to positive blood cultures or clinical signs of bacteremia [116]. The guide-wire change or the complete removal of catheter does not affect the outcome of the infection treatment [117]. Power et al. [118] with their study of 759 TCs showed that the appropriate management of catheters can give functional and complication results similar to AVGs. In their study, survival rates were 85%, 72%, and 48% at 1, 2, and 5 years, respectively, while the infection rate was 0.34 per 1000 catheter-days. Although earlier studies showed a lower risk of catheter-related bloodstream infections with internal jugular TCs compared to femoral, recent studies show no difference between the three sites [119, 120].

Transhepatic hemodialysis catheters seem to be a viable alternative option with low morbidity rates [121]. Another safe and effective long-term access is translumbar inferior vena cava [122]. Retrograde femoral vein catheter insertion is a newly applied lifesaving HD vascular access approach for selected ESRD patients with no available HD vascular access at the ordinary sites with accepted HD adequacy, but it needs more evaluation and studies [123].


**Author details**

Zdravko Podlesek and Darja Žgur Bertok\* Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia

\*Address all correspondence to<EMAIL_ADDRESS>
© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*The* Escherichia coli *SOS Response: Much More than DNA Damage Repair DOI: http://dx.doi.org/10.5772/intechopen.100353*


3.3.2. Tensile Properties of Specimens

To compare the tensile properties of the samples with different carbon contents after laser bionic treatment, the bionic units with the same volume proportions were processed on the surface of the base material. The effect of carbon content on the tensile properties of the biomimetic samples was investigated. Figure 10a–e shows the stress—strain curves of the different carbon-containing untreated samples and laser bionic samples; the corresponding yield strength (YS), tensile strength (TS), and elongation (EL) are shown Table 4.To compare the tensile properties of each biomimetic sample, the tensile property improvement ratio [28] is used to analyze the strengthening effect of different biomimetic samples. The tensile property change ratio refers to the percentage of yield strength, tensile strength, and elongation change of the biomimetic sample compared to the untreated sample, which are represented by *YSC*, *TSC*, and *ELC*, respectively.

**Figure 10.** Tensile curves of bionic samples and untreated samples with different carbon contents: (**a**) A1, (**b**) A2, (**c**) A3, (**d**) A4, and (**e**) A5.

**Table 4.** Tensile test results of the bionic treatment samples and untreated samples.

From Figure 10 and Table 4, it can be concluded that when the carbon content is in the range of 0.15–0.37%, the bionic sample shows a ductile fracture, and when the carbon content is in the range of 0.45–0.58%, the bionic sample shows a brittle fracture. When the carbon content is in the range of 0.15–0.37%, the tensile strength and yield strength of the samples after laser biomimetic treatment are better improved compared to the untreated sample. However, the tensile strength of the bionic samples with carbon content in the range of 0.45–0.58% decreased, especially the tensile strength of the bionic sample with a carbon content of 0.58%, which is even lower than that of the untreated sample.

Figure 11 shows a comparison of the tensile curve of bionic samples with different carbon contents. It can be seen that when the carbon content is between 0.15% and 0.37%, the strength of the biomimetic sample increases, and when the carbon content increases to 0.45%, the tensile strength begins to decline. The elongation of the biomimetic samples decreases continuously with increasing carbon content.

**Figure 11.** Comparative tensile curves of different bionic samples.


5.5.1. Load-Bearing Structure Carrying the Ablative TPS

The dynamic pressure load acts on the component mainly via bending. Thus, the most promising lightweight design concept is that of a sandwich structure. To maximize the load bearing capability to mass ratio, the sandwich is designed with an aluminium honeycomb core between CFRP face sheets. As schematised in Figure 7, the bending load due to pressure acts bi-directionally on the component, i.e., bending it around the longitudinal (*x*-)axis and the circumferential (*y*-)axis. While an increase of the aluminium core thickness increases the stiffness of the structure, stresses in the face sheets are increased as well. Therefore, X-shaped aluminium reinforcements are introduced on the inner face sheet of the ADD against bending deformations, as shown in Figure 16.

**Figure 16.** Structural design of the load-bearing composite sandwich structure carrying the ablative TPS with reinforcements in form of an X-shaped frame and beams along the outer edges.

The layup and dimensions of the structure were determined in an iterative design process using geometrically non-linear static analyses in Abaqus® 2020 on a mesh consisting of a linear shell and beam elements. Typical material data for unidirectional (UD) T700 prepreg material and aluminium honeycomb are used (see Appendix B). Due to the optimised ablative TPS, virtually no thermal loads act on the load-bearing structure

underneath. Therefore, only dynamic pressure loads (see Figure 8b) are considered. In the laminate, the number and orientation of the UD layers was iterated, as well as the cross-section of the X-shaped reinforcements and the frame along the ADD's perimeter.

The obtained design has face sheet laminates with a thickness of 1.75 mm each and a core thickness of 50 mm, resulting in a mass of the structure of 35 kg. For the evaluation of stresses in the composite material, the Tsai–Wu failure criterion [41] is utilised with the goal of maintaining the criterion in all layers below 1.0. For sake of brevity, only the failure criterion values in the most critical composite layer with the highest failure criterion overall are reported (see Figure 17). As the maximum value of 0.92 occurs at border of the ideally stiff boundary condition, stresses in the real component are assumed to be lower than calculated here.

This preliminary structural design study was performed to obtain a benchmark design whose mass can then be compared to the lattice core and corrugated core ITPS solutions. It can be concluded that it was feasible to find a lightweight design for the load-bearing structure when subjected to dynamic pressure loads. The reported mass of 35 kg is that of the load-bearing structure only. The mass of the PICA TPS layer amounts to 32 kg per ADD, thus resulting in an overall mass of 67 kg (neglecting bonding, attachment points, inserts, etc.).

**Figure 17.** Tsai–Wu failure criterion in the critical composite layer of the load-bearing structure.


**EARTH AND ENVIRONMENTAL SCIENCES**

Edited by **Imran Ahmad Dar** and **Mithas Ahmad Dar**

**INTECHOPEN.COM**

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#### **Contributors**

Linchong Huang, Cuiying Zhou, Fereshte Haghighi, Mirmasoud Kheirkhah Zarkesh, Bahram Saghafian, Mohamed Soua, Dalila Zaghbib-Turki, Mohsen Layeb, Hela Fakhfakh-Ben Jemia, Jalel Smaoui, Moncef Saidi, Mohamed Moncef Turki, Jiri Chlachula, Monika Zovko, Marija Romic, Morten Smelror, Nickolay Ivanovich Akulov, Fred Kamona, Carlos Alberto Ríos Reyes, Luz Yolanda Vargas Fiallo, Stephen Imre, Alireza Somarin, Moises Davila, Oscar Jimenez, Vicente Arevalo, Reyna Castro, Erik Medina, Miki Meiler, Moshe Reshef, Haim Shulman, Antonia Longobardi, Mohammad Ali Zare Chahouki, Fresia Ricardi-Branco, Sueli Yoshinaga-Pereira, Fabio Branco, Paulo Ricardo Pereira, Magnus Uzoma Igboekwe, Chukwunenyoke Amos-Uhegbu, Akindele Oyinloye, Massimo Bernardi, Marco Avanzini, Umberto Nicosia, Weijia Sun, Li-Yun Fu, Wei Wei, Binzhong Zhou, Gabriela Olmedo-Alvarez, Luis David Alcaraz, Varinia López-Ramírez, Alejandra Moreno-Letelier, Luis Rafael Herrera-Estrella, Valeria Souza, Andreas Laake, Marco Massa, Sara Lovati, Paolo Augliera, Simone Marzorati, Mahmoud Ahmed, Galal Ibrahim, Hassan Mohamed, Tosheva, Harald Hofmann, Antoine Kies, Vladislav Rapprich, Veronika Kopačková, Kateřina Zelenková, Jiří Šebesta

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*2.8. Determination of Malondialdehyde (MDA)*

A kit (A003-1-1) was used to quantify MDA following the thiobarbituric acid (TBA) method. A glass homogenizer was used to properly homogenize 100 mg of fresh leaves in 900 μL of extraction buffer provided by the company. The homogenate was centrifuged at 5000× *g* for 15 min, followed by three centrifugations of 15 s each at 4000× *g*, with a 30 s interval between each centrifugation, with the final centrifugation of 3500× *g* for 10 min. After that, the supernatant was collected and mixed with the working fluid (combination of R1: clarifying agent, R2: buffering agent, and R3: color developer in the ratio of 0.1:3:1) provided by the company, then the mixture was boiled at 95 ◦C for 20 min. After cooling, the absorbance at 530 nm was determined using a full-wavelength microplate reader (Infinite M200 PRO, TECAN, Männedorf, Swiss) [32].

#### *2.9. Determination of Hydrogen Peroxide, Proteins, GSH, and Antioxidant Enzymes*

A homogenized sample of 500 mg of fresh leaves was centrifuged at 10,000× *g* for 15 min with 4.5 mL of 0.1 M PBS. The hydrogen peroxide (H2O2), total proteins, reduced glutathione (GSH), and antioxidant enzymes, catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX) activities were measured using commercially available test kits purchased from Nanjing Jiancheng Bioengineering Institute, Nanjing, China and their absorbance were determined using a full-wavelength microplate reader (Infinite M200 PRO, TECAN, Männedorf, Swiss) [17,32,33].


*5.3. CEP290*

This cat model, *rdAc* (retinal degeneration, Abyssinian cat) has been studied in detail for many years. Compared to most *CEP290* (centrosomal protein 290) mutations in other species, the cat model has a mild phenotype. The onset and rate of photoreceptor degeneration in the cat with the sparing of the area centralis makes it a model for RP [96,97]. In humans, *CEP290* mutations can result in a spectrum of phenotypes including lethality, severe syndromic disease (e.g., Joubert syndrome) and most commonly LCA; see [98] for a review. Milder phenotypes such as RP are less common. In the cat, an intronic mutation (c.6966+9T>G) leads to the introduction of a stronger splice acceptor site (the wildtype splice acceptor is a GC rather than the much more commonly used GT). The mutation strengthens an adjacent GT, which, when used, adds 4 bps to the exon 50 sequence, the resulting frameshift introduces a premature stop codon [99]. The truncated protein escapes nonsense mediated decay and is expressed. In addition, the wildtype acceptor site is still used for a percentage of the transcripts (unpublished data). The combination of a truncated protein with some remaining function combined with a low-level production of full-length transcripts explains the mild phenotype. *CEP290* is too large to be packaged in an adeno-associated virus vector and one therapeutic approach being investigated is the use of a truncated transcript so that a miniprotein may have partial function and convert a severe phenotype into a milder phenotype similar to that of the cat.


**3.3. Grain boundary migration-theoretical model**

Although the mechanical grain growth has been experimentally observed under various mechanical conditions, the underlying microstructural and atomic scale mechanisms are still open for debate. As mentioned in the introduction section, in an NC material, the fraction of atom residing at the GBs increases as the grain size decreases. Thus, GBs in NC materials promote the total free energy of the system. The reduction of this excess free energy through the removal of grain boundary area represents a large driving force for the grain growth. Grain growth in NC materials can be due to the rotation and coalescence of adjacent grains, as well as normal grain boundary movements. There are several theoretical models that have been proposed to describe the mechanically driven grain growth behavior, for example, stresscoupled GB migration [51–56] and grain rotation-induced grain coalescence [57].

The stress-coupled GB migration model is based on the argument that shear stress causes tangential movement of grains along GBs (GB sliding), and this produces a coupling with the normal motion of GBs (GB migration) [51]. Gutkin and Ovid'ko proposed a continuum disclination model for describing the stress-induced cooperative migration of an arbitrary tile GB [53–55]. The migrating GB was approximated by partial wedge disclination that can move under the applied shear stress, as shown in **Figure 6**. In the initial state, these GBs form two triple junctions. Under an applied shear stress, migration of GB3 from their initial position AB to a new position A′B′ occurs. Stress-induced migration of low-angle tilt GB3 results in the formation of two new triple junctions, A′ and B′. Straight-line defects (junctions) A, B, B′, and A′ are characterized by the disclination strength ±*ω*. The motion of the disclination produces rotational plastic deformation. The same is true for migration of two high-angle tile GBs with large angle gaps. It was shown that there is two critical stress, *τ*c1 and *τ*c2, that controls the GB migration behavior. When the applied stress *τ* reaches *τ*c1, the GB can migrate in the stable mode and their equilibrium position is determined by the level of *τ*. When *τ* > *τ*c2, the GB migration becomes unstable when the GB propagation does not depend on the level of *τ*. In all cases, GB migration leads to the unstable growth of a grain at the expense of its neighbors. Energy methods calculation indicates that critical shear stresses strongly depend on the elastic modulus of the material, as well as on the strength of disclination-like defects appearing at the GB junctions in the process of GB migration.

For the case where the translational mode is mainly represented by GB sliding, Wang et al. suggested a theoretical model which describes the cooperative action of GB sliding and grain rotational deformation in mechanically loaded NC materials, as shown in **Figure 7** [25]. The grain rotation-induced grain coalescence model can be understood as follows [57]: with the applied force, GB dislocations glide results in the relative translational motion of GBs. However, the triple junctions impede the motion of GB dislocation. The blocked GB

Grain Boundary Effects on Microstructural Stability of Nanocrystalline Metallic Materials http://dx.doi.org/10.5772/66426 151

the mean grain size of both the as-deposited and annealed Cu samples increase after the fatigue test, as shown in **Figure 5**. However, the grain growth is greatly suppressed in the annealed NC Cu film, which leads to the enhanced resistance to the fatigue cracking as compared with that of the as-deposited one. The enhanced fatigue strength of Cu film after annealing may be

Although the mechanical grain growth has been experimentally observed under various mechanical conditions, the underlying microstructural and atomic scale mechanisms are still open for debate. As mentioned in the introduction section, in an NC material, the fraction of atom residing at the GBs increases as the grain size decreases. Thus, GBs in NC materials promote the total free energy of the system. The reduction of this excess free energy through the removal of grain boundary area represents a large driving force for the grain growth. Grain growth in NC materials can be due to the rotation and coalescence of adjacent grains, as well as normal grain boundary movements. There are several theoretical models that have been proposed to describe the mechanically driven grain growth behavior, for example, stress-

The stress-coupled GB migration model is based on the argument that shear stress causes tangential movement of grains along GBs (GB sliding), and this produces a coupling with the normal motion of GBs (GB migration) [51]. Gutkin and Ovid'ko proposed a continuum disclination model for describing the stress-induced cooperative migration of an arbitrary tile GB [53–55]. The migrating GB was approximated by partial wedge disclination that can move under the applied shear stress, as shown in **Figure 6**. In the initial state, these GBs form two triple junctions. Under an applied shear stress, migration of GB3 from their initial position AB to a new position A′B′ occurs. Stress-induced migration of low-angle tilt GB3 results in the formation of two new triple junctions, A′ and B′. Straight-line defects (junctions) A, B, B′, and A′ are characterized by the disclination strength ±*ω*. The motion of the disclination produces rotational plastic deformation. The same is true for migration of two high-angle tile GBs with large angle gaps. It was shown that there is two critical stress, *τ*c1 and *τ*c2, that controls the GB migration behavior. When the applied stress *τ* reaches *τ*c1, the GB can migrate in the stable mode and their equilibrium position is determined by the level of *τ*. When *τ* > *τ*c2, the GB migration becomes unstable when the GB propagation does not depend on the level of *τ*. In all cases, GB migration leads to the unstable growth of a grain at the expense of its neighbors. Energy methods calculation indicates that critical shear stresses strongly depend on the elastic modulus of the material, as well as on the strength of disclination-like defects appearing at

For the case where the translational mode is mainly represented by GB sliding, Wang et al. suggested a theoretical model which describes the cooperative action of GB sliding and grain rotational deformation in mechanically loaded NC materials, as shown in **Figure 7** [25]. The grain rotation-induced grain coalescence model can be understood as follows [57]: with the applied force, GB dislocations glide results in the relative translational motion of GBs. However, the triple junctions impede the motion of GB dislocation. The blocked GB

coupled GB migration [51–56] and grain rotation-induced grain coalescence [57].

related to the GB structure readjustment during the annealing process.

**3.3. Grain boundary migration-theoretical model**

150 Study of Grain Boundary Character

the GB junctions in the process of GB migration.

**Figure 6.** Schematic of stress-induced grain boundary (GB) migration (a and b) low-angle and (c and d) high-angle GB (GB3) by grain rotation through the glide of lattice dislocations (b) or motion of a dipole of wedge disclinations (d), respectively [54].

dislocation dissociates from the two climbing GB dislocation at the triple junction. With further plastic deformation, the dislocation split process happens repeatedly and the climbing GB dislocations form two dislocation walls along the GBs, which results in the rotation of the central NC grain. Multiple rotations bring the orientation of abutting grains closer together and reduce the GB misorientation angles, and even eliminate the GBs, leading to coalescence of smaller grains into larger ones.

**Figure 7.** Combined grain boundary (GB) sliding and rotational deformation mode. (a) The GB of the nanocrystalline (NC) Ni dominated by high-angle GBs. (b) dislocations motion along GB impeded by the triple junction resulted in climbing GB dislocations, which caused the rotation of grain 3. (c) Repeated grain rotations leading to grain coalescence. (d) The formation of a larger grain with subGBs (highlighted by dotted line) [25].

#### **3.4. Grain boundary migration-atomic scale mechanisms**

Although theoretical models give some clues about the grain growth processes during mechanical deformation of NC materials, the exact microstructural scale and atomic scale mechanisms of the GB migration is still unclear. Quantitative information aimed to identify atomic scale mechanisms that reveal the influences of GB structure on the GB migration can be obtained by using in situ HRTEM and molecular dynamics (MD) simulation methods. Haslam et al. explored how grain rotation can induce grain coarsening [58]. They found that grain rotation decomposes a GB into multiple but distinct dislocations, which can then move by dislocation slip; these dislocations can annihilate at GBs or remain embedded within grains if the applied stress is relieved. The grain rotation mechanism purports that only some grains are able to rotate and thus coarsened grains can maintain their outer boundaries. This is consistent with the experimental result that GB of coarsened grain is characterized by low-angle boundaries [43, 44]. MD simulation of nanoindentation of NC Al films with a mean grain size of 7 nm showed that the grain rotation may be competing with the GB migration and the GB migration is likely dominant, as shown in **Figure 8** [59]. During cyclic deformation of 20-nm-thick Au thin film, Luo et al. found that grain growth of NC Au is closely correlated with twin formation [60]. Based on the atomic scale observations, as shown in **Figure 9**, they revealed that the formation of nanotwins is an effective way to assist grain coarsening. The grain coarsening process can be described as follows: the mutual nucleation of nanotwins near the GB changes the local Grain Boundary Effects on Microstructural Stability of Nanocrystalline Metallic Materials http://dx.doi.org/10.5772/66426 153

**3.4. Grain boundary migration-atomic scale mechanisms**

152 Study of Grain Boundary Character

(d) The formation of a larger grain with subGBs (highlighted by dotted line) [25].

Although theoretical models give some clues about the grain growth processes during mechanical deformation of NC materials, the exact microstructural scale and atomic scale mechanisms of the GB migration is still unclear. Quantitative information aimed to identify atomic scale mechanisms that reveal the influences of GB structure on the GB migration can be obtained by using in situ HRTEM and molecular dynamics (MD) simulation methods. Haslam et al. explored how grain rotation can induce grain coarsening [58]. They found that grain rotation decomposes a GB into multiple but distinct dislocations, which can then move by dislocation slip; these dislocations can annihilate at GBs or remain embedded within grains if the applied stress is relieved. The grain rotation mechanism purports that only some grains are able to rotate and thus coarsened grains can maintain their outer boundaries. This is consistent with the experimental result that GB of coarsened grain is characterized by low-angle boundaries [43, 44]. MD simulation of nanoindentation of NC Al films with a mean grain size of 7 nm showed that the grain rotation may be competing with the GB migration and the GB migration is likely dominant, as shown in **Figure 8** [59]. During cyclic deformation of 20-nm-thick Au thin film, Luo et al. found that grain growth of NC Au is closely correlated with twin formation [60]. Based on the atomic scale observations, as shown in **Figure 9**, they revealed that the formation of nanotwins is an effective way to assist grain coarsening. The grain coarsening process can be described as follows: the mutual nucleation of nanotwins near the GB changes the local

**Figure 7.** Combined grain boundary (GB) sliding and rotational deformation mode. (a) The GB of the nanocrystalline (NC) Ni dominated by high-angle GBs. (b) dislocations motion along GB impeded by the triple junction resulted in climbing GB dislocations, which caused the rotation of grain 3. (c) Repeated grain rotations leading to grain coalescence.

**Figure 8.** Atomic-level detail of the coalescence of grains. Deformation of Al film with grain size of 7 nm. (a) Contact zone before indentation simulation. (b–d) Rotation of grain 1 due to grain boundary (GB) sliding and transformation of the structure of the GBs. (e) Dissociation and migration of the GB between grains 1 and 2 [59].

grain misorientation and results in the GB dissociated into smaller segments, which is more mobile than their parent one.

Recently, by using in situ HRTEM, Luo et al. have reported the adjustment of GB structures of Cu film during a self-driven GB migration, which involves GB dissociation, partial dislocation emission from GB, and faceting/defaceting [61]. Furthermore, they revealed that GB migration ability is closely related to the local GB segment consisting of "hybrid" structural units.

**Figure 9.** GB dissociation induced by twin formation. (a and d) TEM images of two typical examples of large grains with parallel multi-twins in the fatigued samples. (b and c) and (e and f) The corresponding details of the microstructures, respectively. Scale bars: (a and d–f) 5 nm, (b and c) 1 nm [60].