*Article* **The Influences of Local Glacitectonic Disturbance on Overconsolidated Clays for Upland Slope Stability Conditions: A Case Study**

**Kamil Kiełbasi ´nski 1,\*, Paweł Dobak 1, Łukasz Kaczmarek 2 and Sebastian Kowalczyk 1**

**Featured Application: Spatial development planning, construction of high-rise buildings, construction with the use of deep excavations in areas near slopes (especially in urban areas), where the geological structure is complicated.**

**Abstract:** Reliability of equilibrium state evaluation about settlement slopes in the context of natural and human-made hazards is a complex issue. The geological structure of the vicinity of the upland slope in the urban environment of Warsaw is characterised by a significant spatial diversification of the layers. This is especially due to the glacitectonics in the Mio-Pliocene clays, which are located shallowly under the sandy tills' formations. With substantial variability in the clay roof surface, point recognition by drilling is often insufficient. The use of electrical resistivity imaging (ERI) in the quasi-3D variant provides accurate images of the real ground conditions, which is crucial in optimal geotechnical design. In forecasting the behaviour of the slope, it is necessary to quantify the impact of spatially differentiated systems of disturbed layers on changes in the safety factor (SF), which corresponds to the observed landslide activity of the Warsaw Slope. This study concerns numerous calculation model analyses of the optional clay position in the context of slope stability conditions. A wide range of soil properties variability was taken into account, resulting from both lithogenesis and subsequent processes disintegrating the original soil structure. Regarding the geological conditions of the slip surface, the use of classical computational methods and numerical modelling (FEM) was considered for comparative purposes. The results indicated that local changes in equilibrium conditions were affected by the different morphology of the clay roof surface of the slope and the alternation in strength characteristics on the slip surfaces. The findings of the study contribute to sustainable spatial planning of near-slope regions.

**Keywords:** safety factor; Neogene clay elevation; Warsaw Slope; finite element method; electrical resistivity tomography

#### **1. Introduction**

Slope stability, especially among urban areas, is a subject of extensive engineeringgeology research [1,2]. The scope of these studies includes improvement of geological structures' identification, especially glacitectonic ones, as well as optimising methods of forecasting slope stability conditions. The first aspect uses shallow geophysics, which allows more precise identification and mapping of the course of structural disturbances. The second aspect of the analysis concerns the optimisation of computational methods that are applied in forecasting the equilibrium state of the slopes. Such an approach allows the correlation of the results of the identification of shallowly located glacitectonic structures obtained with the use of different methods. It provides a possibility to apply the data

**Citation:** Kiełbasi ´nski, K.; Dobak, P.; Kaczmarek, Ł.; Kowalczyk, S. The Influences of Local Glacitectonic Disturbance on Overconsolidated Clays for Upland Slope Stability Conditions: A Case Study. *Appl. Sci.* **2021**, *11*, 10718. https://doi.org/ 10.3390/app112210718

Academic Editors: Jaroslaw Rybak, Małgorzata Jastrz ˛ebska, Krystyna Kazimierowicz-Frankowska and Gabriele Chiaro

Received: 11 October 2021 Accepted: 9 November 2021 Published: 13 November 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

acquired with the electrical resistivity imaging (ERI) method to classical slope stability model analyses and to the finite element method (FEM). Combined, the analysed issues can be proposed as a pattern of conducting slope stability research, especially in the case of the wide availability of various research and computational methods, that do not necessarily fit all conditions.

The electrical resistivity method can be helpful in determining a model of spatial variability of strata and slope stability. This method is marked by high prospection efficiency and is commonly used to characterise geological structures, e.g., course and depth of geological boundaries, including the position of clays. Vertical electrical sounding [3–5] and electrical resistivity imaging (ERI) are commonly applied techniques [6–8] to determine the position of the roof of Neogene clays in Poland. The ERI method, also known as the electrical resistivity tomography (ERT) or continuous vertical electrical sounding (CVES) method, is often used in the mapping of landslides and slope stability [9–13]. The theoretical basis of the electrical resistivity imaging method, as well as the history of its development and application, was described by [14,15]. In these studies, the results of an ERI survey were applied to determine the position of the roof of the Neogene clays.

The results of the quantitative assessment of the equilibrium state conditions are the subject of numerous analyses [16–18] and were developed in this work according to the conclusions of [19,20], among others. An important influence on the methodology development of stability analyses has the effect of studies of landslides at different scales and conditions (e.g., [16–24]). Models introduced in the analysed case study take into consideration different factors the spatial variability of the geological structure and periodic changes in soil strength properties caused by changes in moisture content and consistency on potential structural slip surfaces. Those changes can be caused by the seepage of rainwater, especially during increasingly occurring events of heavy rains and sewage system failures. The effects of such situations were analysed using multivariant, computeraided modelling. A number of classical methods of slope stability prediction, based on various assumptions, are in use, although those methods typically do not take geological conditions into account while determining the location of potential slip zones. Another group of analyses uses the modelling of the slope stability conditions based on the finite element method. The comparative approach to the slope stability issue is significant in terms of recognition of optimal slope safety conditions, but also in terms of the evaluation of various prognostic methods. These issues are addressed by the study of the assumptions of both the LEM and the determination of optimal slope slip surfaces using FEM. The obtained results indicate the necessity to further develop an outcome comparison from these two groups of calculation methods [19,25].

Another aspect that is frequently discussed in research is the adoption of simplified plane strain models for spatial issues [21,22]. The presented methodological approach allows the assessment of the influence of various spatial forms on slope stability, and it also answers the question of whether the simplification of the plane-deformation analysis model will have a significant impact on the obtained results. This task was carried out with the use of a 3D model by finite element method (FEM) calculations as well as performing calculations in 2D using two traditional limit equilibrium methods (LEMs; namely, Bishop and Janbu methods) and also once again by FEM.

The FEM calculations were carried out by the ZSoil 2016 software with the implementation of the proportional reduction in strength parameters (c/φ reduction—SRM). The SRM is commonly used for slope stability analysis [16,17,26–28]. The beginnings of SRM application can be associated with the publication of Zienkiewicz et al. (1975) [29]. Based on previous experiments [23,30], the safety factor was determined with consideration of the successively reduced values of strength parameters for iterative solving of the boundary problem of statics using the finite element method. During the calculation process, the state of equilibrium was analysed with the assumption of the geostatic distribution of the stress state in the soil medium. At the initial stage, the value of the reduction factor SF = 1 was determined for which the equilibrium state was defined for the initially adopted soil

parameters. This stage served as a reference level for subsequent iterations in which there was a discrete reduction in the strength parameters of the soil medium by increasing the SF coefficient. This process was conducted until the equilibrium state was lost, which is associated with the development of the slip zone. The last value of the reduction factor SF at which it was possible to obtain the equilibrium state corresponds to the value of the estimated safety factor. The previously mentioned method was applied to solve the problems of the stability of the soil medium in 2D and 3D deformation models.

#### **2. Analysed Area and Materials—Structural Factors of Stability Conditions**

The subject of the study presented in this paper is potential changes in the slope stability conditions in a selected survey area located on the upland in the vicinity of the Warsaw Slope. The survey area was previously investigated with the use of geophysical methods.

Warsaw Slope, which forms the border of the Vistula River Valley, was used as the study site. Warsaw Slope is located on Warsaw Upland, which is built by glacitectonically deformed clays of the Pozna ´n clay formation (Figure 1), covered by layers of glacial till and fluvioglacial sediments.

**Figure 1.** The Neogene clay roof within the Warsaw city centre (excluding soils lying over clay), modified from [31].

The spatially and genetically complex structural setting of Warsaw Slope has been carefully documented by many studies (e.g., [32,33]). Successive development of processes leading to the displacement of soils can be observed, among others, by comparison of historical iconography illustrating the panoramas of the Old Town, Krakowskie Przedmie´scie, and Zoliborz, seen from the side of Vistula River. ˙

There are also historical records mentioning difficulties in placing building foundations, e.g., in the case of St Anne's Church, located directly on the Warsaw Slope. Archival materials, especially panorama paintings and shaded-relief maps, can be used to assess the nature and directions of changes in the Warsaw Slope and correlate them with a rich collection of results of contemporary research and studies. Lithological profiles of numerous boreholes, the results of site observation, i.e., condition of existing buildings, observations from research outcrops discovering old foundations, and data from recently conducted geophysical surveys are collected [9].

Comparisons on modern morphometry indicate that in the most densely developed downtown quarter, the mean height of the Warsaw Slope ranges from 15 to over 20 m, with a typical range of inclination of the slope ranging from 10 to 20 degrees. The highest inclination exceeds 30 degrees in the area of Obo´zna Street and the Old Town. In the synthetic monograph prepared under the supervision of Wysoki ´nski [32], the following geological areas were distinguished:

In general, it can be stated that the status quo of development is maintained, which can be changed by periodically activated slope activity. However, the aforementioned classification does not apply in the areas where soil creeping processes are observed [30,32].

Due to the complexity of the spatial structure of the Warsaw Slope (Figure 2), classic methods based on locating the most favourable slip zones may not be accurate. Mechanistic optimisation related to the assumption of quasi homogeneity of the ground is difficult to accept. After all, the assumption stating that structurally conditioned slip surfaces are major factors in initiating and developing landslide processes is widely accepted. In the case of the Warsaw Slope, these circumstances can occur as a result of glacitectonic deformations of the Pozna ´n clay formation, located in close proximity to the slope. Therefore, the cause of groundmass movements observed on various sections of the slope is often difficult to determine.

**Figure 2.** The roof of the Neogene clay within the borders of Warsaw with two exemplary sections crossing the Warsaw Slope (modified from [9,34]).

On this account, it is necessary to quantify the influence that clay roof deformations have on the stability of the slope. The location of the clay stratum noted in the drilling profiles varies significantly, which is documented in both cross section and map interpretations. Created images are highly dependent on the density of documented boreholes and on the methods of generalising the obtained information [30]. In earlier studies, the border of the clay formation was often captured as a mildly collapsing line parallel to the upland's slope. At the same time, the clay formation collateral to the edge of the upland is built of folds of various heights that create local elevations. The complexity of geological structure is determined by plastic, form-like deformations of clay, caused by the base of a dynamically moving ice sheet.

The denivelations of the clay roof are locally extensively documented (e.g., in the vicinity of the Swi ˛ ´ etokrzyska metro station [31,35]). Such situations may occur along the entire slope. For example, the illustrative cross section in the area of Dworkowa Street about 2 km southward of the analysed area—and Sarmacka Street [36] shows a noticeable uplift of the clay stratum, the upper part of which lies in close vicinity of the upland's slope. The insight on mechanisms of multiplicative folds, along with the growing number of boreholes drilled in the intensively developed areas of Sr´ ódmie´scie and Mokotów districts, indicate that much more local, small elevations occur in the area. Data from newly drilled boreholes are successively added to the databases, making the image of the geological structure in the area more diverse and real. In this case, it is necessary to use geophysical methods, the possibilities of which, however, are hindered in urban areas by the presence of underground infrastructure interfering with the recorded fields.

An example of implementing geophysical prospection is the electrical resistivity tomography that was used to track the disturbances of the clay roof in the area of Pi ˛ekna and Lenona streets in Warsaw.

#### **3. Local Estimation of the Clay Roof Relief Based on Electrical Resistivity Prospection**

ERI measurements were made with the Terrameter LS apparatus of the Swedish company ABEM, alongside three 70 m long measurement lines with 7 m intervals. The spacing of the electrodes on each of the lines was 1 m. Measurements were made by a gradient array with multiple current–electrode combinations, which yields solid outcomes when recognising/mapping horizontal variability [37]. Apparent resistivity data obtained from field measurements were processed with the Res2DInv software [38]. Acquired twodimensional resistivity models of the surface level of the geological medium were used to perform the 3D interpretation in the Voxler program (Figure 3).

The determination of the top surface of the Neogene clays was the primary task for the ERI measurements. The location of the relief of the Neogene clay formation roof was assumed on the basis of the iso-resistivity line of 30 Ωm. Resistivity values below 30 Ωm are the most common resistivity values for clays in Poland [39]. In the Warsaw city region, the juxtaposition of borehole profiles with the distribution of low resistivity values shows that Neogene clays are assigned to soils with electrical resistivity value below 30 Ωm [9,13,40].

The results of the resistivity distribution in the study area were related to geological data from archive boreholes. Such an approach reduced uncertainty of interpretation and increased confidence in placing borders interpreted on the basis of resistivity distribution. Over the Neogene clays (resistivity below 30 Ωm), there is a layer of glacial till, with resistivity from 30 to 80 Ωm. Just above tills, there is a near-surface layer of high resistivity, with resistivity ranging from 80 to over 5000 Ωm. It can be identified as fluvioglacial sands or human-made soils. In this case, electrical resistivity tests do not allow for the differentiation of those deposits and the placement of clear borders between them.

**Figure 3.** Workflow to select the elevation of the Neogene clay roof surface from the results of quasi 3D electrical resistivity tomography prospection.

#### **4. Stability Analysis Results, Their Interpretation, and Discussion**

The tests carried out by the ERI in the area of Pi ˛ekna Street in Warsaw showed a local disturbance of the clay complex roof surface. The relative height of the displacement was determined on the basis of the iso-resistivity line of 30 Ωm and was about 3.5 m. The width of the base of the structure in the direction perpendicular to the slope was estimated at 7.5 m. As a result, the inclination of the Warsaw Slope reached 50 degrees in some places. The interpretation of the 3D ERI in the geophysical image indicates that the considered form of the roof surface had a local character. From a broader analysis of the geological area complexity, it can be assumed that underneath the base of the slope, a dike-like form

parallel to the edge of the upland structure occurs. The obtained results were processed in the AutoCAD software and presented in the form of electrical resistivity distribution as a large-scale surface model (Figure 3).

The next stage of assessing the impact of clay roof surface deformation on the stability conditions in the slope area was the preparation of the upper-layer stratum sequence model. The architecture of the identified form was projected in the spatial model with a geometric approximation. Basic attributes such as the relative height, width, and slope gradient were maintained.

#### *4.1. Stability Analysis by 3D Modelling*

The investigated form is a disturbance with restricted spread, and therefore, the created solid model does not meet the criteria of plane strain analysis. Therefore, it proved necessary to perform a stability analysis, taking into account the three-dimensional stress analysis. In the first stage of the analysis, two generalised solid models were compared:

In the calculation model used, the following was applied:

In the stability calculations, variant values of the geotechnical parameters of clays were assumed, based on the results obtained on own research (from the analysed area adjacent to the slope) and literature data taking into account the glacitectonic disturbance of the structure [30,41,42].

As a starting point in computational iterations, the following assumptions were made:

	- Archival cohesion values were reduced by 60% [42];
	- Values of φ' and c' from TRX investigations; for soils showing the effects of structural disintegration, a reduction of 30% to 45% of the cohesion value and 10% to 30% of the angle of internal friction were applied [41,42];
	- Values of φ' and c' from creep TRX's tests [30].

Section 4.2 presents the parameter value options used in the stability calculations in the following ranges: φ' = 9.7◦–22◦; c' = 0–55 kPa.

The calculations were made with the following spatial assumptions: generally flat clay roof surface slightly inclined towards the slope (option S), which may include

Option PE3.5 refers to the results of the local geophysical investigation, while the alternative variants represent other common types of geological settings found along the Warsaw Slope (Figure 2).

The results of the SF stability factor calculations in options S and PE3.5 were similar (SF(S) = 1.80; SF(PE3.5) = 1.83), which indicates the marginal impact of the 3.5 m disturbance on the slope stability.

In order to assess the impact of the disturbance size on the slope stability, the dike relative height was increased (up to 8 m) while maintaining the previous inclination. In this configuration, 7 options (PE8\_1-PE8\_30) differing in the extent of the disturbance (Figure 4) from 1 to 30 m, with an interval of 5 m, were analysed.

**Figure 4.** Results of slope stability 3D finite element modelling in different structural condition: (1) Cl/siCl—(clay, silty clay) strength parameters on above graph; (2) saCl/clSa—silty clay/clayey sand φ —22◦; c —44 kPa; (3) MSa—(medium sand) φ —30◦; c —0 kPa. Codification explanation: S—slightly inclined, PE—point elevation, D—dike-like form (type of disturbance with the height–disturbance width).

As a result, depending on the assumed strength parameters of the soil, the presence of disturbance in the clay roof surface over 20 m wide resulted in a reduction in the stability index by 3 to 7%m in comparison with option S. The greater presence of clays in the slip zone is a possible reason. The greatest decrease in the SF was observed with φ'= 9.7◦ and c' = 10.0 kPa—the maximally reduced strength parameters of the clay. With the use of the maximum strength parameters (φ'—22◦ and c'—55 kPa), despite the presence of a disturbance in the clay roof surface, an enhancement in the stability conditions was achieved in relation to the S variant. The reason for the modelled slope strengthening was the fact that the assumed clay strength parameters were higher than those of the overlying glacial tills. The numerical simulations of the D8 option were carried out for 4 variants of the strength parameters of Neogene clays while maintaining the parameters of the remaining layers unchanged.

In further analysis, the results of stability modelling at point elevations, the width of which did not exceed 10 m (variant: PE8\_10), were compared with the dike-like elevations. The sensitivity of models with an alternative method of shaping the clay roof surface depends on the considered ranges of strength parameters. The smallest difference in SF, amounting to approx. 6%, was observed for the clay parameters specified in TRX research. On the other hand, the largest difference in the stability indexes, amounting to 14%, was

related to the variant taking into account the maximum reduced parameters of the clay (φ' = 9.7◦ and c' = 10 kPa). It should be emphasised that in each of the analysed variants, the slope stability with the dike elevation was lower than that of the slope with a point elevation of the clay roof surface in the basement. This allows the conclusion that the dike elevations provide an additional safety margin in relation to the point elevation models. Thus, it justifies simplifying the calculations for the plane strain analysis model, which provides an additional safety margin.

#### *4.2. Stability Analysis by 2D Model (Plane Strain State)*

The implementation of calculations in the plane deformation state allowed for additional comparative analyses using the limit equilibrium method (LEM), well established in engineering practice, and the 2D finite element method (FEM). Calculations made in a 2D environment require less computing power, compared with 3D systems.

The simplified Bishop method and the Janbu method were used in the LEM analysis. The simplified Bishop method is a strip method that does not take into account the vertical interaction forces between the stripes and the equilibrium condition of the horizontal forces. In the assumptions, it requires an approximation of the slip surface with a segment of a circle. Despite all these simplifications, it is very often used in practice and, in most cases, sufficient for the initial assessment of slope stability. The obtained estimation of the stability coefficient using this method does not differ from the accuracy obtained by more advanced methods such as the Morgenstern–Price method or the Spencer method [43].

The application of the circular slip surface method is possible mainly in the assessment of the stability of homogeneous structures or a horizontal arrangement of layers. In the case of soil with an inclined layer system or with a complicated course of layers, as in the analysed case, the use of this method may overestimate stability assessments. This fact is largely due to the mismatch between the idealised circular slip surface and the surface produced by the contact of inclined or folded layers. The aforementioned situation occurred in the analysed model. The wrinkled clay roof surface had the potential to initiate a slip. The complexity of the real surface relief, diverging from the cylindrical surface required in Bishop's method, resulted in a reduction in the accuracy of the safety factor estimation.

In the course of computational analyses, four models that differed in the size of the aforementioned discrepancies (caused by structural disturbances) were created. The initial relative height in the analyses of 3.5 m was increased optionally to 5, 6.5, and 8 m. This resulted in, inter alia, changes in the share of clay in the slip zone.

In the considered spatial models, the relief of the disturbed clay roof surface allowed only an approximate fit of the circular slip surface, which also intersected the underlying layers with higher parameters (Figure 5A). This situation had a direct impact on the result of the stability assessment and resulted in its overestimation. In order to assess the size of this overestimation, the results from Bishop's method were compared with the Janbu method, in which the shape of the slip line was adjusted to geological conditions. As a result, stability was analysed even with a more complex, broken slip surface, the course of which was adapted to the contact zone of soils of different genesis and properties (Figure 5B).

The FEM 2D analysis was carried out by ZSoil 2016 software. Geometric assumptions were identical as in the case of the LEM method (Figure 5C). As in the case of 3D analysis, the elastic–plastic constitutive Mohr–Coulomb model was also used to describe the behaviour of the soil medium.

In the plane strain analyses (LEM and FEM 2D), the thickness of the top layer of the clay complex was changed by1mrelative to the set of parameters previously used in the 3D analysis. Calculation models were extended by several sets of strength parameters to assess their sensitivity and possible parameter changes. In total, 8 variants with different parameters of the clay layer were analysed. Additionally, the models differentiated the strength parameters of the deeper clay layer (non-weathered/non-disturbed) using 3 sets of parameters. The first corresponded to the parameters of the clay from the area of ul. Pi ˛ekna [30], the second matched a glacitectonically disturbed clay [42], and the third matched the maximum documented strength parameters of these soils [42]. Parameter combination of the top clay and the deeper layers created 24 calculation variants. Results, in the form of a safety factor (SF), are summarised in Figure 6.

**Figure 5.** (**A**) Circular slip surface for Bishop's method; (**B**) fully specified slip surface for Janbu's method; (**C**) FEM 2D.

**Figure 6.** Results of stability modelling (plane strain analysis).

Analysis of the obtained results indicated that in the Janbu method, differentiating the parameters of the clay layer below the weakened layer did not affect the SF value. In the case of FEM 2D modelling, the influence was also marginal, but with the application of the simplified Bishop method, change was significant. The reason for this is that the slip surface in the Bishop method passed through the deeper layer, while in the Janbu and FEM 2D method, it was limited to the weakened layer only. The FEM 2D modelling indicated a loss in slope stability with the maximally reduced value of the clay strength parameters in all analysed calculation variants. Convergent results were also obtained using the Janbu method but only for the variant taking into account the maximum assumed height of the disturbance (8 m). In other computational cases, despite the disturbance, the slope was stable.

The multivariate analysis of geometric factors and optional strength characteristics allowed presenting the three-dimensional dependencies of SF on the value of the internal friction angle and cohesion (Figure 7). They were mapped in the form of several surfaces corresponding to the different calculation methods used. In addition to the 2D modelling outcome, the results of the 3D FEM are presented. Different sensitivity of individual slope stability calculation methods to changes in strength properties of soils is represented by different inclinations of these surfaces. This influence was best seen in the Janbu method and 2D FEM modelling. Thus, concerning the Janbu method, the great importance of the real relief of the slip surface structural predispositions for the results of stability prediction could be observed. At the same time, the Janbu method obtained the relatively lowest SF values, making it possible to recommend this method as the safest method for geodynamic forecasting.

**Figure 7.** The three-dimensional dependencies of SF on the value of the internal friction angle and cohesion for different calculation methods.

The SF values obtained by 3D FEM modelling deviate from the results of other methods. In the range of low clay internal friction angle (9–11◦), values of SF were comparable to the results obtained by the Bishop method. However, for φ' values above 12◦, the SF results were the highest of all the methods used. By assumption, the results of 3D modelling illustrate the natural geological situation better, especially taking into account the weaknesses in the slope [20]. Further, the 3D modelling outcomes differed from the results of 2D calculations. The SF values obtained in the 2D model were lower than the results of 3D modelling. The reason for the higher value of SF estimates may be the application of 3D models with a reduced density of the finite element mesh compared with the 2D variant. The increase in the finite element density causes a decrease in the predicted slope stability index value [26,27]. Without deciding which approach is closer to the real equilibrium state, it is worth noting that the consideration of lower estimated SF value by designers is treated as a safer procedure.

#### **5. Conclusions**

**Author Contributions:** Conceptualisation and design: K.K. and Ł.K.; literature review: Ł.K. and S.K.; methodology and validation: K.K., Ł.K. and S.K.; formal analysis: K.K., Ł.K. and S.K.; investigation and data collection: K.K., Ł.K. and S.K.; data analysis and interpretation: K.K., Ł.K., P.D. and S.K.; writing—original draft preparation: K.K., P.D., Ł.K. and S.K.; writing—review and editing: P.D., K.K. and Ł.K.; supervision: P.D. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the University of Warsaw.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


*4.5. Production of NanoESI Capillaries*

NanoESI capillaries for offline measurements were prepared in-house from borosilicate glass tubes of 1 mm outer and 0.5 mm inner diameters (BF 100-50-10, Sutter Instruments, Novato, CA, USA), using a P-1000 Flaming/BrownTM micropipette puller system (Sutter Instruments, Novato, CA, USA). Capillaries were gold-coated using a sputter coater BalTec SCD 0045 (Bal-Tech, Balzers, Liechtenstein) with the following conditions: current was set to 20 mA for 150 s, table distance was 5 cm, while vacuum was ca. 10−3 mbar and Argon gas pressure maintained at ca. 10−2 mbar [16].


**5.2 Vernacular architecture: search for identity**

During architectural modernization in the Arab World starting 1950s, many traditional buildings and heritage symbols were demolished for they were symbols of retardation and poverty. In paving the path for modernization in Arab cities, architectural heritage was abandoned and expertise of its construction lost. Many historic buildings suffered degradation and decay due to neglect and misuse by informal development and occupation by less fortunate people.

In spite of the several demands by professionals, public, and suggested policies in 1970s and 1980s on the conservation of the traditional urban fabric of the Arab city, the traditional fabric was demolished, partially or completely in favor of Western building style as a trend to modernity. This was one of the actions leading to loss of modern architecture identity in the Arab World. The new urban planning strategies were set to accommodate the modern life vibrant style where grid-iron planning, big streets, cookie-cutter plots, new construction materials, and high-rise buildings replaced traditional fabric neglecting cities' architectural heritage and society's cultural values.

#### *Sustainability and Vernacular Architecture: Rethinking What Identity Is DOI: http://dx.doi.org/10.5772/intechopen.82025*

It is a fact that when traditional city core demolished drastically, this affects people's social behavior and may affect their feeling toward their city and life style [27]. Rapid culture change enables one to identify core versus peripheral elements, those elements changing rapidly versus those remaining relatively constant.

 In an attempt to reveal identity in modern architecture in the Arab World, some architects, local and international, began to use elements, forms, and motives in particular, from vernacular architecture in the design of new buildings as a resemblance of the (glory) of the past. Some modern architectural trends in the Arab World, in efforts to "reveal" identity, have defined the local architectural identity by demonstrating distinctive characteristics of vernacular building elements to be symbols of local identity [28] without deep analysis of the real essence of how these elements originated and by what means they reflected people, place, and environment.

This approach became a (facial) mask; it was mainly evident on facades, openings, and architectural features such as arches, ornaments, and domes rather than the design concept or interior spaces (**Figure 4**). New construction materials and technology such as concrete, steel, big glass opening, and air-conditioning became essential in most new buildings with total abandonment to local materials and ambient environment.

 There were a few attempts to be inspired by the core design elements of vernacular architecture such as environmental solutions. However, there were several examples for regional architecture, designed by western and Arab architects trying to create an alternative to the prevailing international models [24] such as the work of Mohammed Makkiya, Hassan Fathy, Rasem Badran, Jafar Tukan, Rifat Chadirji, and Elie Azagury. This awareness of the importance of vernacular architecture and tradition to enhance the built environment was not merely a nostalgic approach to the past; it was about endurance of local identity.

#### **5.3 Vernacular architecture: sustainability and identity**

 Vernacular architecture is of great potentiality to modern "…as the late twentiethcentury people, though, limitations of traditional cultures in helping us to know what to do are evident" [29]. Nevertheless, vernacular architecture features offer dramatic metaphors for regional forms of shelter, as well as rational responses to the harsh climate giving modernism a subtle but telling shove in direction of regionalism [9].

The multiplicity of sustainability trends has a great impact on the architectural identity and image of the Arab city. Abdul Salam and Rihan defined three trends: the modern technology, the neotraditional, and the contemporary interpretation trend investigating reasons of their emergence, main features, and impacts on the architectural identity in Arab World [30].

 Revitalization of architectural heritage and conservation cultural values in an environmentally sensitive manner requires detailed planning. It needs knowledge of materials and their interactions; knowledge of construction, craft techniques, skilled technicians, and available resources; and an ongoing commitment to the region identity through a sustainable approach. Heritage revitalization within sustainable approach needs an in-depth interpretation of core values of this heritage that goes beyond the typical "imitation" and visual metaphors of traditional forms and architectural features and ornamentations.

Vernacular architecture has the essence of sustainability to be the link to more environment-respected buildings. To ensure society continual survival, we need to adapt sustainable solutions for growth through respecting the environmental balance of nature. The reevaluation of vernacular architecture can offer an indefinite source to develop worthwhile ecological solutions for the built environment responding to society needs [31].

It is not just nostalgia that draws people to vernacular architecture. Much of what is valued in this architecture is its sustainability and response to the climate, natural setting, and locally available building materials. Their usefulness as model for new buildings only adds to their value.


**4. Parental approach to chronic disease and the hospitalisation of the child**

Chronic disease in children and adolescents, besides bringing new variables into the lives of the patients, imposes on the parents the need for developing new routines and acquiring new knowledge about the conduct and the care of children.

According to Alves (2009), mothers who live often with the hospitalisation process of children learn to provide care and are able to supervise the work of providing assistance, judging if they are "right or wrong" in accordance with what they have learnt.

By exercising their role of providing care to the child, mothers have a function which permeates meanings in the universe of nursing, whilst the nurse is, in these cases, in a place which does not have clearly demarcated boundaries in the delivery of healthcare. This confusing and ambiguous situation can create conflicts and disagreements with regards to knowledge and information. However, the disposition of mothers to provide care should not be taken as a rule in the same way that it is not specialised care (Alves, 2009).

The development of care by carers, in general, does not form part of the same option. The experience of chronic disease, gradually, inserts them into the hospital routine where they learn and act. The permanent presence of companions imprints another dynamic in the assistance process, because it provides the opportunity to learn some new technical abilities and to amplify other knowledge about the functioning of the hospital and of therapeutic techniques (Lima, Rocha e Scochi, 1999).

The presence of the family within the context of the hospitalisation of children and adolescents represented an advance in the relationship between the users and the hospital space, but as an isolated initiative it didn't recognise or take into account the need to understand the dynamics involved in the process of chronic disease in children and adolescents. The presence of the carer needs to be tracked by a therapeutic project which integrates patient care because the carer is attached to assistance and meaning is related to the patient's disease.

As a vehicle for providing access to the knowledge of patients and carers, dialogue and guidelines are indispensable resources. The construction of a therapeutic project, which integrates knowledge and establishes performance guidelines within each stage of patient care, can be a great resource for structuring and organising more harmonious and coresponsible relationships.

At this point the ability and capacity for communication, dialogue and a host of other demands and opportunities for the autonomous expressions of the family, comes into play. Sharing the provision of care with carers requires the exercise of co-participation. A space for dialogue is needed which enables the different actors to express their doubts and feelings. This space can not be attached to the duration of time in hospital, but rather instituted as a means for the management of daily services.

The investment in the relationships between healthcare professionals, patients, and their carers, founded and guided by such factors as the initial contact and dialogue between patients and doctors, may empower the role and autonomy of children and their carers.

The appreciation of knowledge of paediatric patients about the process of chronic disease and the relationships which they experience within the context of hospitalisation are as

**4. Parental approach to chronic disease and the hospitalisation of the child**  Chronic disease in children and adolescents, besides bringing new variables into the lives of the patients, imposes on the parents the need for developing new routines and acquiring

According to Alves (2009), mothers who live often with the hospitalisation process of children learn to provide care and are able to supervise the work of providing assistance,

By exercising their role of providing care to the child, mothers have a function which permeates meanings in the universe of nursing, whilst the nurse is, in these cases, in a place which does not have clearly demarcated boundaries in the delivery of healthcare. This confusing and ambiguous situation can create conflicts and disagreements with regards to knowledge and information. However, the disposition of mothers to provide care should

The development of care by carers, in general, does not form part of the same option. The experience of chronic disease, gradually, inserts them into the hospital routine where they learn and act. The permanent presence of companions imprints another dynamic in the assistance process, because it provides the opportunity to learn some new technical abilities and to amplify other knowledge about the functioning of the hospital and of therapeutic

The presence of the family within the context of the hospitalisation of children and adolescents represented an advance in the relationship between the users and the hospital space, but as an isolated initiative it didn't recognise or take into account the need to understand the dynamics involved in the process of chronic disease in children and adolescents. The presence of the carer needs to be tracked by a therapeutic project which integrates patient care because the carer is attached to assistance and meaning is related to

As a vehicle for providing access to the knowledge of patients and carers, dialogue and guidelines are indispensable resources. The construction of a therapeutic project, which integrates knowledge and establishes performance guidelines within each stage of patient care, can be a great resource for structuring and organising more harmonious and co-

At this point the ability and capacity for communication, dialogue and a host of other demands and opportunities for the autonomous expressions of the family, comes into play. Sharing the provision of care with carers requires the exercise of co-participation. A space for dialogue is needed which enables the different actors to express their doubts and feelings. This space can not be attached to the duration of time in hospital, but rather

The investment in the relationships between healthcare professionals, patients, and their carers, founded and guided by such factors as the initial contact and dialogue between patients and doctors, may empower the role and autonomy of children and their carers.

The appreciation of knowledge of paediatric patients about the process of chronic disease and the relationships which they experience within the context of hospitalisation are as

instituted as a means for the management of daily services.

judging if they are "right or wrong" in accordance with what they have learnt.

not be taken as a rule in the same way that it is not specialised care (Alves, 2009).

new knowledge about the conduct and the care of children.

techniques (Lima, Rocha e Scochi, 1999).

the patient's disease.

responsible relationships.

important as the experiences of carers. The right of children to express themselves can provide valuable information for healthcare practices which may be reconsidered in favour of a more comprehensive and friendly service.

Beginning with this understanding, it is possible to construct relationships within healthcare which will not be guided by the subjection and control of the patient, but where you can affirm the capacity of the paediatric patient to express, create and reinvent standards which make possible for autonomously administering the margin of risk to life, amplifying capacities for coping with the disease together with the most important relationships.

The recognition, on the part of healthcare teams, of the conditions in which the body is encountered, the subjectivity of the patient, is the first step towards incorporating a new understanding of the patient, taking into consideration the factors involved in the patient's life.

Taken as a proposal to consider care as a value (Pinheiro, 2007), understanding it as an integral action which has meanings related to the understanding of healthcare such as the right to medical and other specialised treatments, allows the patient to actively participate in the decisions taken in regard to the conduct of their own case.

Healthcare begins when a dialogical relationship between the patient and healthcare professionals is initiated, which transcends the simple game of the active questions of healthcare professionals and the passive responses of patients towards the construction of a space of exchanges, where the medical knowledge of the doctor incorporates itself into the lived experiences of the individual. With this, it is possible to establish relationships which are guided by partnership between people which have the objective of finding the shortest route to the restoration of health.

Caprara e Franco (1999) emphasise the need to overcome both the informative model that relays information and the paternalistic model which protects the patient from their own disease, towards a model of communication which includes other important actors in the life of the patient. It is an overcoming which requires a change in attitude and understanding about the healthcare process and the place of the other within this relationship.

For Deslandes (2004a), the possibilities of communication are related to the social position which individuals occupy. In the relationship between doctors and patients there exists, historically, a differentiation between the place and value of their speech.

However, the construction of an active communication begins by recognising the place of the patient as that of a subject in the relationship. According to Deslandes (2004b), the necessary movement in order to change this logic of attention within healthcare not only incorporates a new understanding of patients and their lived experiences, but also a change which observes the organisational culture in which are concentrated the relationships of knowledge-power, gender and social status. These are these factors present in the organisational culture which are able to feed certain types of relationships between the actors in institutions.

Healthcare taken as a value, (Pinheiro, 2007) proposes that we recognise the ethos of the cared for and of the provider of care, which requires including in the relationship the

Infantile Hospitalisation and Chronic Disease 249

Finally, to highlight the contribution of Ayres (2005), in relation to the concept which he calls Projects for human happiness. For the author, this concept refers to the idea of lived experiences, positively valued, which are not dependent on a state of complete well-being in the life of the subjects. In cases of disease, these projects can be constructed from the various values and guidelines which orientate healthcare. He makes the salient point that happiness materialises in the lives of individuals through the construction of everyday life projects, a concept which can't be defined universally or as an external entity. Projects for human happiness are associated with the capacity to overcome obstacles and move in the direction

The way to construct, in healthcare, Projects for human happiness involves the evaluation of values which orientate the processes of chronic disease and healthcare, as much as in regards to the integration of care by the different actors who participate, as well as the closer cultural, economic and social ties between healthcare professionals, patients and relatives. Above all, the view of the child should be complete, going beyond the supposed organic

There exist many different ways for the child to access the contents of pain and happiness. Nevertheless, a leading Projects for human happiness agent for carriers of chronic disease requires going beyond the implementation of technical methods and procedures or structural knowledge of disciplines, in order that new meanings and new ways of listening

Adam, P. & Herlizch, C. (2001). *Sociologia da doença e da medicina*. 1a. Edição EDUCS: ISBN 85-

Alves, C. A. (2009). Desafios da humanização no contexto do cuidado da enfermagem

Antunes, J. L.F. (1989). Por uma geografia hospitalar. *Tempo social, Revista Sociologia*. Vol. 1,

Ariès, P. (2009) Por uma história da vida privada. In: *História da vida privada: da Renascença ao*

Baszanger, I. (1991). Déchiffrer la douleur chronique: deux figures de la pratique médicale. *Sciences Sociales et Santé*, Vol. 9, No. 2, pp. 31-78. ISSN 10.3406/sosan.1991.1190 BRASIL. Constituição (1988). Constituição da República Federativa do Brasil: promulgada

BRASIL. (1990) Estatuto da Criança e do Adolescente. Lei nº 8.069 de 13 de julho de 1990.

Bowlby, J. (1984) *Apego*. 1a. Edição, Martins Fontes, ISBN 0-465-00543-8, Rio de janeiro.

Criança e da Mulher. Instituto Fernandes Figueira. Rio de Janeiro.

pediátrica de média e alta complexidade. Dissertacão de Mestrado em Saúde da

*Século das Luzes*. Ariès, P. & Chartier, R. (orgs), pp. 7-19. 1a. Edição, Companhia das

em 5 de outubro de 1988. Contém as emendas constitucionais posteriores. Brasília,

Dispõe sobre o Estatuto da Criança e do Adolescente e dá outras providências.

of values held by both the individual and collective.

7460-100-4, Bauru, São Paulo.

No. 1: pp. 227-234. ISSN 0103 2070

DF: Senado.

Brasília, DF.

Letras, ISBN<PHONE_NUMBER>351, São Paulo.

**6. References**

limitations and inability to express feelings and experiences.

and new points of view can be expressed in spaces of care and attention.

dimensions of individual life with its habits and customs and communitarian life, both being originating dimensions in the character and identity of the subjects. It is to be able to incorporate the ethos of the other in a process which extends itself making that therapeutic moment a unique moment of contact and dialogue.


*3.5. Ionotropic Cross-Linking*

Ionotropic gelation exploits the capability of polysaccharide-based polyelectrolytes to crosslink in the presence of counter ions under specific ranges of concentration and/or pH [107]. The ionic cross-linking of polysaccharide droplets in aqueous solution gives rise to hydrogel particles (or beads) characterized by a microstructure with interconnected nanofibrillar network [108–111]. Hydrogel physicochemical properties depend upon chemical composition of the selected polysaccharide, its concentration as well as the size (i.e., ionic radius) and the valence (i.e., coordination number) of counter ions and eventually, the presence of water of hydration surrounding cross-linking ions [2,112].

Biocompatible and biodegradable alginate, pectin, chitosan are polyelectrolytes having active functional groups, such as carboxylate, sulphate and amine that can be involved in the ionotropic gelation mechanism [113]. Obviously, the type of counter ion and the gelling conditions must be chosen in relation to the specific polysaccharide used for droplet formation. Alginate and pectin, being polyanionic polysaccharides, tend to cross-link in presence of polyvalent cations. In this case, the gelation is induced by the electrostatic interactions establishing between cations and the polymer anion blocks [114]. On the contrary, chitosan with its amine functional group can undergo ionotropic gelation in presence of anionic counter ions such as tripolyphosphate (TPP), sulphate and citrate. The gel network formation is due to the electrostatic interactions established between anionic counter ions and the chitosan cationic blocks [115–117].

### 3.5.1. Alginate Ionic Cross-Linking

Alginate is certainly the most well-known and studied example of polysaccharide that can be cross-linked via a ionotropic mechanism [118]. It is a linear polysaccharide copolymer consisting of α-l-guluronic acid ( **G**) and β-d-mannuronic acid ( **M**) repeating units forming regions of **M**- and **G**-blocks and alternating structure (MG-blocks) [65,119,120] (Figure 7).

**Figure 7.** Chemical structure of alginate monomers: l-guluronic acid and d-mannuronic acid.

Alginate can be obtained from different brown seaweed species or from certain bacterial strains (e.g., *Pseudomonas aeruginosa*) [121]. The alginate source defines the **G**-to-**M** ratio and the molecular weight of the polysaccharide leading to significant differences in the physicochemical and mechanical properties of the resulting gels [119]. Commercially, alginates are available as alginic acid or in the form of sodium, potassium, or ammonium salts. Generally, most of divalent cations (Ca2+, Sr2+, Cd2+, Co2+, Cu2+, Mn2+, Ni2+, Pb2+ and Zn2+) and some trivalent cations (Fe3+, Cr3+, Al3+, Ga3+, Sc3+ and La3+) can interact with **G**-blocks regions of alginate in a highly cooperative manner, generating a 3D network according to the so-called "egg-box" model [122]. Alginate affinity towards such polyvalent cations is directly dependent on the amount of G-blocks present in the alginate structure [123,124]. As demonstrated in [125] by numerous competitive inhibition studies, the main involved gelation mechanism is the dimerization of **G** residues. In detail, the addition of polyvalent cations (often Ca2+ ions) to the alginate solution determines the binding of two **G**-blocks on opposite sides; the result is a diamond shaped hole consisting of a hydrophilic cavity that binds the cations by multicoordination using the oxygen atoms from the carboxyl functional groups. This arrangement causes the formation of a junction zone shaped like an "egg-box" (Figure 8).

**Figure 8.** Egg-box model representing the interactions between alginate **G**-blocks and calcium ions. Reprinted from [113]. Copyright (2019) Martău, Mihai, Vodnar.

Each cation binds with four **G** residues in the egg-box formation to form a 3D hydrogel network of these interconnected regions [15,126]. It has been reported that in the case of Ca2+, the formation of a stable junction requires eight to twenty adjacent **G** unites [65].

Generally, the greater the atomic radius of the cation, the stronger is the cross-linked polymeric matrix. In fact, as reported by [123,127–129], divalent ions of larger ionic radii such as Ba2+ and Sr2+ are able to produce stronger alginate gel particles than the Ca2+-based ones (Figure 8). By contrast, having a smaller atomic radius, Mg2+ is not able to cross-link alginate [112,130]. Overall, alginate affinity to cations increases in the following order: Mn2+ < Zn2+, Ni2+, Co2+ < Fe3+ < Ca2+ < Sr2+ < Ba2+ < Cd2+ < Cu2+ < Pb2+ [123]. For practical applications, the use of highly toxic cations such as Pb2+, Cu2+, and Cd2+ is limited. The use of Sr2+ and Ba2+, which are mildly toxic, has been reported in cell immobilization applications although only at low concentrations [131]. Ca2+ is certainly the divalent cation most used to form ionic alginate gels for its good binding affinity to alginate and lack of toxicity under normal conditions of use [15]. Although it is generally recognized that most divalent and trivalent cations are able to form alginate gels according to the pioneering "egg-box" model (valid mainly for **GG** sequences), it is important to consider that the chemical composition of such polymers and hence the **M**/**G** ratio can significantly vary [132]. This means that binding affinity with cations as well as polymeric conformation can vary too. Some binding studies have shown that Sr2+ is able to bind to G-blocks only, Ca2+ to both **G**- as well as **MG**-blocks, and Ba2+ to both **G**- and **M**-blocks [65,123]. In general, binding affinity with cations is lower for both **MM** and alternating **MG** blocks, requiring a rather high polyvalent ion concentration to be more efficiently complexed. Compared to **GG** blocks, both **MM** and **MG** ones present a more open geometry that make them more available for interchain aggregations along polymer (self-assembly of alginate chains) causing significant irregularities in the arrangement of uronic units in alginate chains; this happens for the gels cross-linked by relatively low ion radius cations [125]. Since in the pharmaceutical field the ionotropic gelation is commonly used to entrap an API between the polymer chains, this arrangement can affect the drug release in a controlled manner.

### 3.5.2. Pectin Ionic Cross-Linking

Pectin is a linear polysaccharide mainly consisting of galacturonic acid units which are connected via α-(1–4) bonds and with a certain degree of methyl esterification of carboxyl groups (Figure 9) (DE, degree of esterification) depending on the polysaccharide quality and source [133]. It is commonly extracted from apple pomace and citrus peels under slightly acidic conditions. There are currently three commercially types of pectins: (1) low methoxyl (LM) pectin, where less than 50% of galacturonic acid groups are esterified with methyl groups; (2) high methoxyl (HM) pectin, where more than 50% of existing galacturonic acid groups are esterified with methyl groups; and (3) amidated pectin (A), where acid groups are partly amidated. Gelling properties highly depend on the ratio of esterified and amidated acid groups [134].

**Figure 9.** Pectin structure.

As reported by Braccini and Perez [114], despite the structural analogy between polyguluronate and polygalacturonate chains, the egg box model valid for alginates (guluronate system) cannot be directly transposed to the pectate gels. In this case, the most favorable antiparallel associations of galacturonate chains may, at best, be considered as "shifted egg boxes". The observed "shift" seems to lead to an efficient association with several van der Waals contacts; it reduces the original large cavity and provides two symmetrical sub-cavities of appropriate size for binding a cation and it creates an efficient periodic intermolecular hydrogen bonding network. Generally, the methyl esterification of carboxyl groups weakens the crosslinker-pectate interaction and might hamper subsequent dimer-dimer. Therefore, ionotropic gelation is more pronounced for lower-methylated pectins and at pH around 3–3.5; increasing the pH leads to deprotonation of acidic groups which prevents aggregation of chains and eventually gelation. Pectin has been also mixed with alginate to form in presence of cross-linking ions an interpenetrated network made up by heterogeneous interactions [135–137].

### 3.5.3. Chitosan Ionic Cross-Linking

Among several polysaccharides amenable to ionotropic cross-linking, chitosan is another noteworthy example even if by far less investigated than negatively charged polysaccharides such as alginate and pectin [138]. Chitosan is typically obtained from the alkaline deacetylation of the highly abundant, naturally occurring polymer chitin, but other sources can directly provide it as such (e.g., yeasts) [113]. Chitosan is composed of β-1,4-linked glucosamine and *N*-acetylglucosamine residues [139]. Both the degree of acetylation (DA) and the degree of polymerisation (DP) of chitosan are crucial factors determining the structural and functional properties of this family of polymers and their resulting engineered materials [140]. Commercially available chitosans vary in their DA, usually between 5 and 20%, and in their DP or molecular weight, typically ranging between 10 and 500 kDa. Unlike chitin, chitosan is soluble in water under mild acidic conditions thanks to the protonation of its amino groups (pKa = 6.2–7) able to promote the solvation of polymer chains. In these conditions, chitosan behaves as a polycation and, consequently, can form a gel by ionic interaction in presence of multivalent anions. Tripolyphosphate (TPP) is by far the most employed cross-linker to ionically reticulate chitosan due to its high net negative charges (ranging from one to five depending on pH) per monomeric unit and nontoxicity [116,141,142]. TPP has been widely exploited in pharmaceutical field to obtain chitosan microparticles [143–145], nanoparticles [143,146] and nano/micro-gels [147,148] intended for controlled drug delivery [149].

### *3.6. Di*ff*erent Approaches to Hydrogel Formation by Ionotropic Cross-Linking*

Hydrogels can be generated using ionotropic gelation technique by three main methods that differ in the way crosslinking ions are introduced to the polymer, realizing the so-called external, internal or inverse gelation [18,150].

In the external gelation or diffusion controlled method, polysaccharide solution is added dropwise into the gelling bath. The hydrogel matrix is formed through the diffusion of the cross-linking agents from the external continuous phase into the inner structure of polymeric droplets [151]. As expected, at the outermost layer of the hydrogel, gelling kinetics is rapid and gel formation is instantaneous. Then, counter-ions start to diffuse towards the center of the particle creating an inhomogeneous gelation profile in which the interaction between ions and polymer functional groups is maximum at the surface and zero at the core [152,153].

The internal gelation also called in situ gelation is an approach widely used to produce calcium alginate particles [154]. In this case, an insoluble calcium salt (e.g., CaCO3 and CaSO4) is mixed with the polysaccharide solution, and the obtained mixture is then extruded into an acidic gelling bath [155–157]. The acidic environment increases the solubility of calcium salt, allowing its release that leads to the formation of the polysaccharide gel network. This mechanism guarantees a controlled and homogeneous alginate exposure to cations and hence a uniform gel network formation [120]. Despite the good homogeneity, the internal cross-linked matrices results less dense, with larger pore sizes and thus more permeable than those obtained for external gelation, with lower encapsulation efficiencies and faster release rates [157,158]. This happens because matrix permeability is affected by competition between Ca2+ and H+ ions due to the acid added. It seems that while the acid in the gelling bath liberates Ca2+ from the insoluble salt, it also competes with Ca2+ for interaction with the alginate/polymer. This drawback can be overcome by manipulating the pH of the medium and the amount of calcium salt employed [150].

Another approach is the inverse gelation, based on the dripping of the medium containing the cross-linking agents into the polysaccharide solution. This method is usually applied to emulsions for producing alginate microcapsules with an oily content and soft shell [5,159,160]. In comparison to other cross-linking methods, it exploits low amounts of biopolymer leading to the formation of a soft particle shell. Clearly, as highlighted by Martins at al. [161] in a recent published paper, the properties of the obtained microcapsules (e.g., mechanical resistance and release of bioactive substances) can vary based on the type of emulsion used (W/O or O/W) for the inverse gelation

### **4. Influence of Drying Process on Gel Particle Characteristics**

As discussed above, polysaccharide-based hydrogel particles can be used in the hydrated form for di fferent applications [119,162–166]. However, to avoid their chemical or microbiological degradation a drying step is often required [167,168]. Hydrogel particles can be dried using several techniques such as conventional, dielectric, freeze or supercritical drying, each one with a significant impact on the physicochemical and textural properties of the final dried beads [169]. Phenomena such as modifications of the highly interconnected hydrogel network, solute migration, polymorphism, damages by overheating and many other e ffects can occur [170]. Therefore, the choice of the drying method represents one of the critical step on the pathway to the production of PbHPs. As illustrated in Figure 10, each drying process leads to polymeric material with di fferent inner structure; conventional or dielectric methods allow to obtain "xerogels" whereas freeze and supercritical drying generally allow to achieve "cryogels" and "aerogels", respectively [171–175].

**Figure 10.** Pathway for the production of xerogels, cryogels and aerogels from polysaccharide based hydrogels via several steps including: (**a**) gelation (SOL →GEL), (**b**) solvent exchange pre-treatment, if required (e.g., the replacement of the water contained in the pores of the hydrogel with a suitable organic solvent), (**c**) drying final step with a specific technology. The images of xerogel, cryogel and aerogel beads were here reprinted (with some modifications) from [176] with permission from Elsevier. Copyright (2016).

Each drying method presents specific advantages and disadvantages (Table 1), and the choice must be done based on the desired performances for the final product, system cost-e ffectiveness and realizable scale-up.

In the following paragraphs, production and properties of xerogel, cryogel and aerogel particles are discussed.

**Table 1.** Main characteristics of the drying methods for polysaccharide hydrogels.

### *4.1. Conventional and Dielectric Drying to Produce Xerogels*

Conventional drying (e.g., using ambient air and an oven) as well as dielectric treatments generally cause the collapse of the nanoporous structure of the parent hydrogel due to the high capillary pressure gradient established during the solvent removal. The collapsing of the polymer structure produces a massive volume shrinkage leading to the formation of a highly aggregated and densely packed material without pores; the formed compact structure is known as "xerogel". However, as discussed in a large number of papers [175,177–179], porous texture of the dried material can be tuned by a proper selection of solvent, temperature, carrier gas used during evaporation and, specifically for microwave heating, the irradiating regimen. These parameters alone or in combination can allow to obtain either microporous, micro-mesoporous or micro-macroporous textures of the dried beads. For instance, as reported by [176] the porous structure of cellulose-based wet gels may resist to collapse to a certain limit when alcohol, having low surface tension and low vapor pressure, is used as organic solvent. In addition, an interesting study of [180] showed that degree of substitution (DS) of cellulose can play an important role for the production, via ambient drying, of low density, open porous and hydrophobic cellulose material defined "Xerocellulose". During this research, tritylcellulose with di fferent DS was synthesized in homogeneous conditions and then subjected to dissolution-coagulation-drying producing "Xerocellulose". Results showed that, depending on DS, the chemical modification leads to the development of unusual microstructure due to the di fferent manner of self-assembly of cellulose molecules and lack of hydrogen bonding.

Xerogel porosity may be specifically tuned, as demonstrated by studies of our research group aimed to verify the feasibility of the tandem technique Prilling/Microwave assisted drying for the production of alginate-based beads loaded with non-steroidal anti-inflammatory drugs (NSAIDs) [181,182]. Microwaves at di fferent regimens of irradiation a ffected matrix porosity, solid state of the loaded drug (i.e., ketoprofen or piroxicam) and drug-polymer interaction, leading to beads with significant di fferences in drug release profiles. Interestingly, high MW irradiation level led to dried beads with highly porous and swellable inner matrix able to rapidly release the encapsulated drug in the simulated gastrointestinal fluids. By contrast, low MW irradiation levels produced beads with few pores in the inner matrix acting as NSAID delayed delivery systems.

### *4.2. Freeze-Drying to Produce Cryogels*

During the freeze drying, the liquid entrapped into the hydrogel body is frozen and sublimed under regulated vacuum [118,183] reducing the volume shrinkage of the beads to 40%–50%. Unless special precautions are often taken to prevent the growth of ice crystals, freezing may destroy the pore structure and damage the nanostructured gel matrix as freezing always implies the growth of crystals [184]. The increase of the solvent volume upon crystallization induces the formation of a dendritic network of the crystalline solvent phase. The dendrites are, depending on the cooling rate, typically in the range of few up to a few tens of micrometers' size; they push the walls of the network at the crystal boundaries destroying the morphology/inner structure [185–189]. The resulting material is open porous product with a pore size in the range of several micrometers termed "cryogels".

In certain cases, modifying the freeze-drying conditions it is possible to modulate the ultrastructure of the porous matrix, moving from nanofibrillar to sheet-like skeletons with hierarchical micro- and nanoscale morphology. For instance, by increasing the cooling rate of the hydrogel precursors with e.g., liquid propane, or by using the spraying freeze drying approach, it is possible to avoid the macroporous 2D-sheet morphology of cellulose cryogels, producing aerogel-like dried systems with intermediate textural properties (BET-specific surface areas of 70–100 m2/g) [190]. Interestingly, the freeze drying of alcogels from resorcinol-formaldehyde using t-butanol as solvent resulted in a significant improvement of the mesoporosity of the resulting dried gels if compared to the freeze drying of hydrogel counterparts [187].

### *4.3. Supercritical Assisted Drying to Produce Aerogels*

Supercritical drying is the best method to preserve the porous texture and structural properties of the wet gel network in a dry form without cracks as well as without substantial volume reduction or packed network structure due to the intrinsic absence of surface tension in the pores of the gel. Supercritical drying produces nanostructured materials with low-density (typically <0.2 g cm−3), high-porosity (>96% *v*/*v*) in the mesoporous range, with full pore interconnectivity and large surface area (>250 m2/g), commonly called "aerogels".

During supercritical drying, the organic solvent in the hydrogel pores (deriving from the pre-treatment named solvent exchange procedure, see Figure 10), is removed under supercritical conditions. As well known, a fluid reaches its supercritical state when it is compressed and heated above its critical point. Supercritical fluids have liquid-like densities and gas-like viscosities [195]. Supercritical carbon dioxide is the most commonly used fluid for supercritical drying due to its mild critical point conditions (304 K, 7.4 MPa), nontoxicity (it is considered to be Generally Recognized as Safe or GRAS), environmental friendliness, widely availability and cheapness/cost-e ffectiveness [191,196,197]. Generally, prior to the supercritical drying, the solvent exchange (that is the replacement of the water contained in the pores of the hydrogel with a suitable organic solvent) is needed due to the low a ffinity of water to supercritical carbon dioxide (SC-CO2) [196,198]. The presence of even small amounts of water in the pores of the wet gel can cause a dramatic change in the initially highly porous polysaccharide network upon supercritical drying. The usual approach in SC-CO2 drying procedure is the displacement of the water using a solvent with high solubility in CO2, commonly alcohol or acetone [191] and then the immersion of the gel in SC-CO2. The extraction time depends mainly on the thickness of the gel samples. Therefore, it can be still reduced from the several hours needed for thick monoliths to only few minutes for polysaccharide particles of millimeter size.

### **5. Case-Studies: Polysaccharide-Based Hydrogel Particles Produced by Prilling**/**Ionotropic Gelation and Their Application as Drug Delivery Systems (DDS)**

Polysaccharide-based hydrogel particles can be used as drug carriers, which application in pharmaceutics depends on the characteristics of the polysaccharides and the drugs, the particle configuration, as well as on the inner structure, namely xerogels, cryogels and aerogels. Table 2 summarizes the di fferent kinds of PbHPs produced via prilling/ionotropic gelation, particle configuration (only core or core-shell), their main physico-chemical and technological properties, and the potential pharmaceutical applications.

As shown in Table 2, hydrogels can be obtained as simple monolayered (only core) or multi-layered (core-shell) systems, in the hydrated or in the dried form. Based on the specific drying treatment, hydrogel beads can be transformed into xerogel, cryogel or aerogel form. The choice of a specific polysaccharide and particle system must be driven by the final desired application and performance requirements. Prior to any process design, it is necessary to study physico-chemical characteristics of the polymeric materials, like viscosities, densities, gelation and, physico-chemical and biopharmaceutical properties of the carried drug.

*Molecules*

 **2020**, *25*, 3156

### *5.1. Design of PbHPs in Form of Xerogels*

As reported in Table 2, successful outcomes have been achieved through a formulation design based on prilling in tandem with conventional drying that provide e fficient drug delivery of both steroidal (e.g., prednisolone and betamethasone) and non-steroidal (e.g., ketoprofen, ketoprofen lysine salt and piroxicam) anti-inflammatory drugs, targeting chronic inflammation and early morning pathologies.

The accurate selection of biopolymer, the opportune set-up of process parameters and gelling conditions allowed to produce interesting delivery systems in the xerogel form with controlled drug release both for low soluble and highly soluble NSAIDs. Zn2+ as external cross-linking agent for alginate/ketoprofen (K) solutions gave PbHPs with good technological properties such as drug loading, particle size, morphology, hardness of cross-linked matrix [202]. In vitro and in vivo release behavior resulted to be strongly influenced by the amount of NSAID loaded inside the polymer; the loading of high amount of drug into feed solutions promotes, during the gelling phase, the formation of a compact gel polymeric network via intermolecular interactions, as hydrophobic or hydrogen bonding, which stabilize the well-known alginate "egg-box" structure. This phenomenon leads to tough polymer beads (Figure 11a), reducing the leaching of the drug from the drops into the gelling medium. Accordingly, the formulation obtained with the highest drug content (F20, K/alginate ratio 1:5) showed the highest entrapment of the drug within the matrix (encapsulation e fficiency, 53%) and a delayed release of the drug in simulated intestinal fluid (see Figure 11b). This in vitro release pattern was clearly reflected in the in vivo prolonged anti-inflammatory e ffect evaluated using a modified carrageenan-induced acute edema assay in rat paw. F20, administered 3 h before edema induction, showed a significant anti-inflammatory activity, reducing maximum paw volume in response to carrageenan injection, whereas no response was observed for pure ketoprofen (see Figure 11c).

**Figure 11.** Main in vitro and in vivo results obtained for Zn-alginate-based xerogel beads loaded with ketoprofen: (**a**) SEM microphotographs showing the compact inner matrix; (**b**) relese profile performed by USP Apparatus 4 and, (**c**) edema volume reduction in rats (\*\* *p*-value ≤ 0.01, \*\*\* *p*-value ≤ 0.001 compared with control). These images were here reprinted (with some modifications) from [202] with permission from Elsevier. Copyright (2015).

Zn2+ as external cross-linking agent for pectin solutions was able to produce PbHPs containing ketoprofen lysine salt (KL), a highly soluble NSAID [204]. In this case, the best results were obtained using amidated low methoxyl pectin (esterification degree 24% and amidation degree 23%) producing beads with good morphological properties and size, high drug content and encapsulation e fficiency (93.5%), and interesting KL sustained release profiles.

−−

−−

−S−

### *5.2. Investigation on the E*ff*ect of Di*ff*erent Cations on Gelation Process*

Many researchers evaluated the influence of di fferent divalent cations on PbHP properties. For instance, Chan et al. [210] studied the ability of calcium chloride and zinc sulphate to cross-link alginate microspheres prepared by emulsification.

In this study, the aqueous phase, consisting of 2.5% *w*/*w* sodium alginate and 1% *w*/*w* sulphaguanidine was dispersed in isooctane with the aid of surfactants and a mechanical stirrer. The fine globules of sodium alginate produced were gelified by addition of calcium chloride and zinc sulphate, alone or in combination. The microspheres formed were collected by filtration, washed and oven dried at 40 ◦C. The results of characterization studies showed that the simultaneous use of these two salts led to di fferent particle morphology and slower drug release compared to particles cross-linked by the calcium salt alone. These e ffects were attributed to a greater extent of interaction between zinc cations and the alginate molecules able to produce a less permeable alginate matrix. Cerciello et al. also investigated the specific e ffect of these two divalent cations, i.e., Ca2+ and Zn2+, used alone or blended in di fferent ratios (Ca2+:Zn2+, ratio 1:1, 1:4 or 4:1), on the properties of alginate beads obtained via prilling/external gelation [201]. The synergistic e ffect of the two cations, when used in the gelling bath in the ratio Ca2+:Zn2+ 1:4; positively a ffected particle morphology, size, inner structure, ability to encapsulate the model drug (SAID, prednisolone, P) and to control its release from the polymer matrix. Figure 12 shows SEM and SEM-EDS microphotographs of cryofractured blank beads obtained using the di fferent ratios Ca2+/Zn2+ in the gelling solution. As showed, formulations gelified using Ca2+:Zn2+ in the ratios 1:1 and 4:1 exhibited an internal structure enriched in Ca2+, due to the higher di ffusivity of this cation, compared to Zn2+. Only with a ratio Ca2+/Zn2+ 1:4 was possible to observe an equilibrium between the two cations quantities into the polymeric matrix. This specific ratio, in fact, exploited the Ca2+ ability to establish quicker electrostatic interactions with **G** groups of alginate and the Zn2+ ability to establish covalent-like bonds with both **M** and **G** blocks of alginate. Drug release profiles clearly reflected the advantages deriving from the simultaneous use of both cations. Their proper mixing allowed to produce a polymeric matrix tougher and more resistant compared to those obtained with a single cation (zinc or calcium) and with an interesting P prolonged release.

**Figure 12.** SEM and SEM-EDS microphotographs of cryofractured blank xerogel beads produced with di fferent Ca2+/Zn2+ ratios: (**a**) 1:1, (**b**) 1:4 and (**c**) 4:1. Reprinted from [201] with permission from Elsevier. Copyright (2017).

### *5.3. Prilling to Obtain Floating PbHPs*

A significant number of studies was conducted to develop floating PbHPs, mainly alginate based particles, using gas-forming agents such as CaCO3 or NaHCO3. In the most of them, calcium has been used as external cross-linker for the gelation phase [157,211,212]. More recently, an important milestone was achieved with the simultaneous use of two different divalent cations to produce floating and prolonged release alginate PbHPs for the oral administration of prednisolone, P [207]. Critical parameters were established: prilling/ionotropic gelation was used as microencapsulation technique, zinc acetate in the gelling solution as the alginate external crosslinker, and calcium carbonate in the feed acting as the internal crosslinking agent able to generate gas when in contact with the acidic zinc acetate solution. The double gelation process (internal- and external) promoted by Ca2+ and Zn2+ ions gave alginate beads with extremely high encapsulation efficiency values (up to 94%) and a very porous inner matrix conferring buoyancy in vitro in simulated gastric fluid up to 5 h. Particularly, the best formulation F4 (P/Alginate ratio 1:5; Alg/CaCO3 ratio 1:0.50) was able to control the drug release in acidic medium for the entire time corresponding to the floating period. Although porous, the tougher matrix obtained thanks to the double gelation process is able to reduce swelling and erosion processes in simulated gastric fluid (SGF). F4 was also able to prolong the in vivo anti-inflammatory effect up to 15 h compared with raw prednisolone. Therefore, this alginate-based system has been proposed as a new technological platform able to extend the anti-inflammatory efficacy of SAID such as prednisolone (characterized by high efficacy and high tolerability, but short half-life) for many hours and successfully treat patient suffering from chronic inflammatory diseases, also reducing the frequency of the oral administration.

An interesting production innovation was obtained designing floating PbHPs with controlled release properties without using any gas-generating agent. Our research group designed a hollow multipolymer matrix made up of alginate, ALM-pectin and HPMC. Results showed that particle shape and sphericity can be correlated to nozzle viscosity of the feed solutions; the higher the nozzle viscosity, the slower the break-up of the polymeric laminar-jet and, thus, droplet formation. The high entanglement existing between the chains of three different polymers makes the polymeric jet highly cohesive (viscoelastic stresses dominate) delaying drops detachment from the nozzle. At the lowest feed concentration (4.75 *w*/*w*), corresponding to a nozzle viscosity of 24.4 mPa·s, polymer chains are relaxed and surface tension dominates, allowing the formation of droplets that, falling in the gelation bath, give rise to spherical particles. Optimized formulation F4 (Drug/Polymers ratio 1:15; Pol1/Pol2/Pol3 ratio 1.25:3:0.5) showed beads spherical in shape with a sphericity coefficient mean value of 0.94 and a mean diameter around 2200 μm. This formulation acts as a floating-system able to release the encapsulated model drug (piroxicam, PRX) in a controlled and delayed manner.

Floating properties of F4 are due both to the swelling of the hydrocolloid particles and to hollow inner structure (Figure 13). The hydration of the hydrocolloid particle surface in SGF results in an increased bulk volume and, at the same time, the presence of internal pores make beads able to entrap air. As a result beads had bulk density <1, and, therefore, remained buoyant on the acidic medium. In addition, the inner cross-linked multi-polysaccharide matrix acts as reservoir for slow and sustained PRX. Drug release was controlled by a diffusion mechanism process through the swollen polymers gel layer, as shown by in vitro release assay. Figure 14 shows the presence of pores and air bubbles entrapped within the gel barrier after 60 min of floating in acidic medium.

**Figure 13.** SEM microphotographs showing the hollow inner matrix of polysaccharide-based floating beads produced with different Pol1/Pol2/Pol3 ratios: (**a**,**b**) 1.75:4:1, (**c**,**d**) 1.75:3:0.5 and (**e**,**f**) 1.25:3:0.5. Reprinted from [206] with permission from Elsevier. Copyright (2018).

**Figure 14.** Microphotographs obtained using bright-field (**a**,**b**) and fluorescent microscopy (**c**,**d**) showing the presence of pores and air bubbles entrapped within the gel matrix of hydrated beads, able to confer their floating ability in SGF. Reprinted from [206] with permission from Elsevier. Copyright (2018).

As expected by morphology and results from in vitro assays, a promising application of floating PbHPs is the treatment of chronic inflammatory-diseases in elderly patients needing a rapid onset of drug action followed by a maintenance dose. In this regard, the in vivo anti-inflammatory activity of this type of new floating PbHPs, evaluated using the modified protocol of carrageenan-induced acute edema in rat paw previously developed [202], showed an incredible extension, up to 48 h, of the anti-inflammatory e ffect compared to standard PRX, as e ffect of both floating and sustaining release abilities.


# **Preventing the Adverse Effects of SARS-CoV-2 Infection and COVID-19 through Diet, Supplements and Lifestyle**

Edited by William B. Grant and Ronan Lordan

Printed Edition of the Special Issue Published in *Nutrients*

www.mdpi.com/journal/nutrients


**9. References**

138 Polycrystalline Materials – Theoretical and Practical Aspects

iPP - 29.9 1171 31.7 NA40 - 32.9 1616 27.1 NABW - 25.4 1031 98.2 NA40/NABW 1:3 31.1 1443 58.0 H-Ba - 26.9 1018 93.6 NA40/H-Ba 1:9 30.8 1309 79.0 PA-03 - 27.1 1022 103.7 NA40/PA-03 3:7 31.0 1344 64.0

Table 5. Mechanical Properties of iPP Nucleated with different NAs (addition amount 0.2 wt

Nowadays α/β compounded NAs for polypropylene have attracted more and more attention. This short review summarized the research on α/β compounded NAs in recent years. Three kinds of well studied α/β compounded nucleating agents (NAs), Phosphate/Amide, Sorbitol/Amide, and Phosphate/Carboxylate were selected to review their influence on the crystallization kinetics, crystallization morphologies, and mechanical proprieties of isotactic polypropylene (iPP). The results showed that α/β compounded NAs could not only increase the crystallization temperature of iPP but also shorten the crystallization half-time, consequently reduce molding cycle time of iPP more obviously. The obtained Avrami exponent indicated that the type of nucleation of iPP could be changed while the geometry of crystal growth of iPP remains. The size of spherulites in nucleated iPP appeared much smaller than that in pure iPP. However, iPP nucleated by different α/β compounded NAs showed different morphologies. The same result was obtained by the investigation of the mechanical properties of iPP. Some α/β compounded NAs were able to enhance stiffness and toughness of iPP simultaneously while the other α/β compounded NAs could only devote to one aspect. It was summarized that the key factor of affecting the α/β compounded NAs is the crystallization temperature of iPP nucleated with NA individually (TC). The NA with higher Tc plays a leading role in the crystallization process. Consequently the mechanical properties, crystallization properties and crystalline microstructure of iPP appear close to it. Competitive nucleation will occur when the difference of Tc between two NAs is not pronounced. According to this rule, the optimization method for compounding α and β NAs was developed. That is to find out the ratio of α and β NAs with TC α = TC β so as to let competitive nucleation occur during crystallization. Then the method was applied to an example of adjusting the stiffness and toughness of iPP based on different of α/β compound NAs. Rely on it the optimal ratios of α/β compounded NAs can be easily determined by calculation TC at different ratios instead of testing them on mechanical properties. Sequentially it makes more effective to enhance

stiffness and toughness of iPP based on α/β compounded NAs.

Flexural modulus (MPa)

Impact strength (J/m)

Tensile strength (MPa)

Nucleating agents

%) (Shi & Xin, 2011)

**7. Conclusions**

Compound ratio

**7**

*Russia*

**Influence of Irradiation on**

V.V. Krasil'nikov1 and S.E. Savotchenko2

*and Professional Retraining of Specialists*

*2Belgorod Regional Institute of Postgraduate Education*

*1Belgorod State University*

**Mechanical Properties of Materials**

The one of actual problems of radiation material science is to reveal plastic deformation laws, hardening and fracture ones of materials under intense external action, particularly irradiation. Herein we imply different kinds of irradiation, for instance, such a (*e*, ) beam irradiation, ion or neutron irradiation and so on. Evolution of a construction material microstructure at a high temperature trial operation is substantially conditioned by free migrating defects [1]. The processes of interaction of point defects with each other, with dislocations and interface underlie all of metal radiation hardening mechanisms [2]. In the section 1, the nonlinear model of dose dependence saturation of the yield strength is proposed on the base of the vacancy and interstitial barrier interaction. Processes of mutual recombination of vacancy and interstitial barriers and formation of vacancy and interstitial

A series of different radiation defects (retardation barriers of dislocations), and their sizes, and a form of their volume distribution contribute into a yield strength increment for all of sorts of irradiation. The contribution of a barrier type is determined by conditions of irradiation and tests. At the low temperature irradiation (at the test temperatures up to 0.3 Tm, Tm is melting temperature), interstitial atoms, and vacancies, and their clusters contribute mainly into the hardening. In the section 2, evolution of radiation barrier (vacancies and interstitials) clusters is analyzed under low temperature radiation in the presence of the most important secondary effectes: recombination and formation of divacancy complexes. It is proposed a barrier hardening model in that mechanisms of mutual annihilation of the vacancy

In the section 3 unlike two preceding sections where the dose dependences are considered, the phenomenological model is formulated to describe a yield strength temperature dependence of polycrystalline materials that have undergone irradiation and mechanical experiences in a wide temperature interval including structure levels of plastic deformation. In this section, a new phenomenological model is proposed to give a suitable description of yield strength temperature dependence of some of irradiated materials in a temperature

**1. Introduction**

clusters are taken into consideration.

and interstitial barriers and their clusterization play a main role.

interval including plastic deformation structure levels.


**4. Conclusions**

In this study, a bifunctional epoxy precursor was functionalized with a rubber phase. Then, self-healing molecules were added to the rubber-toughened bifunctional epoxy resin to confer it auto-repair function. The functionalization process allows obtaining elastomeric domains not exceeding 500–600 nanometers. After the curing cycle of the formulated selfhealing samples, the effect of the temperature of epoxy precursor functionalization on the properties of the samples was evaluated in terms of self-healing efficiency, DMA, and TGA. It was found that the higher functionalization temperature of 160 ◦C can better promote the reaction between the rubber phase and the epoxy precursor during the functionalization process. The more efficient interactions affect the resin structure and its thermal and mechanical properties. Self-healing efficiency analysis highlights the crucial role of functionalization temperature in increasing self-healing ability. Samples functionalized at 160 ◦C manifest healing efficiency higher than 69%. The highest value (88%) was detected for the sample with DBA filler. The healing efficiency of the same sample functionalized at 120 ◦C decreases to 52%. Results from DMA evidence that a lower value of Tg (observed for the sample functionalized at the higher temperature of 160 ◦C) allows for obtaining the highest healing efficiency. Thermal stability in air higher than 250 ◦C was observed for all formulated samples.

**Supplementary Materials:** The following supporting information can be downloaded at https:// www.mdpi.com/article/10.3390/aerospace10050476/s1: Figure S1: Dimensions of the TDCB geometry specimen (on the left); EP-R-160 sample located in the INSTRON instrument (on the right). Numerical values of the lengths are expressed in mm; Figure S2: DSC curves of the samples EP-R-160, EP-R-160- DBA, EP-R-160-T, EP-R-160-M, before the curing process (after the functionalization reaction) and after the curing process; Figure S3-1: Photos of the self-healing fillers after incorporation into the Gurit precursor ECC at room temperature; Figure S3-2: Photos of the self-healing fillers before incorporation into the Gurit hardener MHHPA; Figure S3-3: Photos of the self-healing fillers after incorporation into the Gurit hardener MHHPA; Figure S3-4: Visualization of the complete solubilization of the self-healing fillers in the Gurit hardener MHHPA; Figure S4: (a) Load-Displacement curves for the sample Ep-R-120-DBA; and (b) histogram illustrating the healing efficiency values for the samples Ep-R-120-DBA and EP-R-160-DBA.

**Author Contributions:** Conceptualization, methodology, supervision, project administration, writing—original draft, writing–review and editing L.G.; Formal analysis; investigation M.R., C.N., R.L. and A.S.; Resources M.C.; Conceptualization, formal analysis, data curation, writing–original draft, investigation, writing–review and editing E.C. and L.V. All authors have read and agreed to the published version of the manuscript.

**Funding:** The research leading to these results was funded by the European Union's Seventh Framework Programme for Research, Technological Development and Demonstration, under Grant Agreement N 313978.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.