**Polymer Based Bioadhesive Biomaterials for Medical Application—A Perspective of Redefining Healthcare System Management**

**Nibedita Saha 1,\* , Nabanita Saha 2,\*, Tomas Sáha <sup>1</sup> , Ebru Toksoy Öner <sup>3</sup> , Urška Vrabiˇc Brodnjak <sup>4</sup> , Heinz Redl <sup>5</sup> , Janek von Byern <sup>5</sup> and Petr Sáha 1,2**


Received: 1 December 2020; Accepted: 13 December 2020; Published: 16 December 2020

**Abstract:** This article deliberates about the importance of polymer-based bioadhesive biomaterials' medical application in healthcare and in redefining healthcare management. Nowadays, the application of bioadhesion in the health sector is one of the great interests for various researchers, due to recent advances in their formulation development. Actually, this area of study is considered as an active multidisciplinary research approach, where engineers, scientists (including chemists, physicists, biologists, and medical experts), material producers and manufacturers combine their knowledge in order to provide better healthcare. Moreover, while discussing the implications of value-based healthcare, it is necessary to mention that health comprises three main domains, namely, physical, mental, and social health, which not only prioritize the quality healthcare, but also enable us to measure the outcomes of medical interventions. In addition, this conceptual article provides an understanding of the consequences of the natural or synthetic polymer-based bioadhesion of biomaterials, and its significance for redefining healthcare management as a novel approach. Furthermore, the research assumptions highlight that the quality healthcare concept has recently become a burning topic, wherein healthcare service providers, private research institutes, government authorities, public service boards, associations and academics have taken the initiative to restructure the healthcare system to create value for patients and increase their satisfaction, and lead ultimately to a healthier society.

**Keywords:** bioadhesion; biomaterials; biomedical application; healthcare system management; innovation; polymer based bioadhesive

**JEL Classification:** I1; I10; I11; I18; I21; I28; H51

### **1. Introduction**

Currently, in the 21st century, healthcare management plays an important role in focusing and aligning the myriad continuous improvements that optimize the application of bioadhesion as related to innovative biomaterials' medical use. This article intends to reveal the importance of bioadhesive biomaterials' application in the healthcare system. Nowadays, the application of bioadhesion is one of greatest interests for various researchers who intend to develop new biomaterials, therapies and technological possibilities, such as biomedical application. Accordingly, progressive innovation in the bioadhesion of biomaterials has trended sharply upward, and is expected to double by 2020, especially with a focus on delivering quality healthcare. Although redefining health, the World Health Organization (WHO) defined 'health' as a state of complete physical, mental and social wellbeing that not only considers the illness, but prioritizes the concept of value-based healthcare [1]. On the other hand, from the functional perspective, bioadhesives can be considered as an identical material, which is biological in nature and holds together for extended periods of time by interfacial forces. Essentially, it is an area of active multidisciplinary research approach, wherein engineers, scientists (including chemists, physicists, biologists, and medical experts (supportive medical), materials producers, and manufacturers combine their knowledge [2]. Finally, from the practical point of view, this article proposes some research assumptions, which state that the bioadhesion of biomaterials for redefining healthcare management is not a new concept. Its implementation has been used for several years for medical applications, such as dentistry and orthopedics, and it is now entering new fields, for example, tissue sealing and directed drug delivery systems. In addition, the said issues and solutions affect and involve healthcare delivery organizations, health plans and employers, i.e., healthcare service providers, private research institutes, government authorities and public service boards, research institutes, associations and academics. The outcome will be, in the long-term, to restructure the healthcare system, which will not only create value for patients and increase satisfaction, but it will also improve the health effects through enabling new efficiencies and lowering costs.

### *1.1. Notion of Biomaterials*

Regarding the notion of "biomaterials", it is necessary to mention that there are two significant topics that are inter-related with the concept of the word biomaterial. The first conceptual meaning of biomaterial deals with the term 'bio', which exemplifies, as a way of filling in the gaps where the question arises, whether we are discussing the process of taking out of life or putting into life. The second term, "material", has a broader sense, which indicates a substance. Now the question arises of how this material can enable us to keep our life more flexible. Research shows that from the healthcare benefit point of view, several scholars have made an effort to define the term "biomaterials" and its application as well as utility in our day-to-day life. In medical science, research has shown that it has ample potential to keep our life more flexible, in that it will easily enable us to respond to altered circumstances. Although, biomaterials' presentation in medical science did not get that recognition until the Consensus Conference on Definitions in Biomaterials Science, held in 1987. According to the European Society for Biomaterials, earlier, the term biomaterials and its medical application were not so profoundly known in the medical science, though its application was already existing [3], as the definition is a result of considered debate, which definitely has some reliability from a healthcare point of view. On the other hand, this conceptualization of biomaterials concludes that a biomaterial is "a non-viable material and its application in a medical device, is envisioned to interrelate with the biological systems" [4].

### *1.2. Overview of Bioadhesion*

Bioadhesion may be defined as the binding of a natural or synthetic polymer or biological-origin adhesive to a biological substrate. When the substrate is a mucus layer, the term is known as mucoadhesion [5]. On the other hand, while referring to the application of bioadhesion in broad terms, it is necessary to mention that the terminology "bioadhesion" itself represents an extensively differentiated phenomena, as it covers the adhesive properties of both the synthetic components as well as the natural surfaces (such as cells). Furthermore, research shows that bioadhesion could also refer to the usage of bioadhesives in order to link the two surfaces together, especially in drug delivery, dental and surgical applications [6]. As such, the significance of bioadhesive biomaterial application has emerged and been recognized due to its consequences for the specific development of new biomaterials, therapies and technological products for redefining the healthcare sector. *Polymers* **2020**, *12*, 3015 3 of 19 differentiated phenomena, as it covers the adhesive properties of both the synthetic components as well as the natural surfaces (such as cells). Furthermore, research shows that bioadhesion could also refer to the usage of bioadhesives in order to link the two surfaces together, especially in drug delivery, dental and surgical applications [6]. As such, the significance of bioadhesive biomaterial application has emerged and been recognized due to its consequences for the specific development of new biomaterials, therapies and technological products for redefining the healthcare sector.

#### **2. Bioadhesion of Biomaterials 2. Bioadhesion of Biomaterials**

Medical Devices, Springer Book [7]).

While discussing the significance of the bioadhesion of biomaterials, it is mandatory to highlight that in the contemporary world, healthcare is a fundamental issue in translational research, especially when it is innovative, as well as the fact that the bioadhesion of biomaterials application is being used in healthcare in order to fight against life-threatening diseases. In addition, over the past two decades, innovative biomaterials applications have been viewed as a significant issue in translational research in the field of regenerative medicine, where biomaterials have been extensively applied in numerous medical devices for the benefit of healthcare. In this regard, it is necessary to state that the study of biomaterials is essentially associated with the study of biocompatible materials, especially for biomedical applications, which encompasses not only the synthetic materials, such as metals, polymers, ceramics and composites, but also includes biological materials, for example proteins, cells and tissues. The below-mentioned Figure 1 shows examples of the bioadhesion of biomaterials. While discussing the significance of the bioadhesion of biomaterials, it is mandatory to highlight that in the contemporary world, healthcare is a fundamental issue in translational research, especially when it is innovative, as well as the fact that the bioadhesion of biomaterials application is being used in healthcare in order to fight against life-threatening diseases. In addition, over the past two decades, innovative biomaterials applications have been viewed as a significant issue in translational research in the field of regenerative medicine, where biomaterials have been extensively applied in numerous medical devices for the benefit of healthcare. In this regard, it is necessary to state that the study of biomaterials is essentially associated with the study of biocompatible materials, especially for biomedical applications, which encompasses not only the synthetic materials, such as metals, polymers, ceramics and composites, but also includes biological materials, for example proteins, cells and tissues. The below-mentioned Figure 1 shows examples of the bioadhesion of biomaterials.

**Figure 1.** Bioadhesion of biomaterials (based on the idea from the *Bioadhesion of Biomaterials*, and **Figure 1.** Bioadhesion of biomaterials (based on the idea from the *Bioadhesion of Biomaterials*, and Medical Devices, Springer Book [7]).

On the other hand, the term bioadhesion refers to the situation wherein natural and synthetic materials stick to each other, and especially to biological surfaces. Henceforth, the application of bioadhesive polymers in healthcare emerges, specifically with the use of medical devices for the effects on the biological exterior and crossing point. In this review article, the authors attempt to prove that, from the healthcare point of view, bioadhesion's presentation is advantageous. Considering the grafting of medical devices in the human body, it is necessary to remember that though this embedding procedure is a very useful and important aspect of healthcare, we cannot On the other hand, the term bioadhesion refers to the situation wherein natural and synthetic materials stick to each other, and especially to biological surfaces. Henceforth, the application of bioadhesive polymers in healthcare emerges, specifically with the use of medical devices for the effects on the biological exterior and crossing point. In this review article, the authors attempt to prove that, from the healthcare point of view, bioadhesion's presentation is advantageous. Considering the grafting of medical devices in the human body, it is necessary to remember that though this embedding procedure is a very useful and important aspect of healthcare, we cannot ignore the probability of high risks due to the interface for microorganisms. As implantable medical devices

ignore the probability of high risks due to the interface for microorganisms. As implantable medical devices are the idyllic location for the growth of microbes, infections are triggered quickly by bacteria are the idyllic location for the growth of microbes, infections are triggered quickly by bacteria that mainly originate in the body itself. Consequently, some phases effect the bioadhesion of implantable medical devices, including surface topography, chemical interaction, mechanical interaction and physiological interactions.

Research shows that, considering these aspects, medical practitioners will likely try their best to control the medical devices through bioadhesion processes by enhancing the desirable interaction of bioadhesion and eliminating the adverse interactions. Therefore, to comprehend the debate on the bioadhesion of biomaterials in order to redefine healthcare management, it is necessary to mention some methods of the bioadhesion testing, which includes the evaluation of (a) surface roughness/surface morphology/surface topography, (b) chemical interactions, (c) physiological factors, (d) physical and mechanical effects, and (e) the contact angle and testing of biofilm formation [7,8]. In this conceptual article, focus has been placed on natural polymer-based bioadhesive biomaterials, i.e., polysaccharide/carbohydrate-based adhesives and protein-based adhesives. Carbohydrates in the form of polysaccharides are mostly available from plants (available in three different forms: cellulose, starch and natural gum), the exoskeleton of various marine animals, and/or are synthesized by some microorganisms. Cellulose is the principal structural material of the cell walls of plants. It is a homopolymer of β-d-hydroglucopyranose monomeric units that are linked via a linkage between the C-1 of the monomeric unit and the C-4 of the adjacent monomeric unit [8]. Due to the presence of the large number of hydroxyl groups, cellulose molecules readily form hydrogen bonds with other cellulose molecules so as to give highly crystalline structures, as the bonds are generally sensitive to water. These unique structural properties of cellulose are hindering its use as an adhesive itself.

As such, the future applications of these adhesives demand the modification of natural polymers so as to give components that can undergo further cross-linking to form water-insensitive bonds [8]. For example, cellulose converted to various cellulose derivatives in the form of ester and ether (e.g., cellulose acetate, carboxymethyl cellulose, hydroxyethyl cellulose, etc.) can be used in the formation of carbohydrate polymer as an adhesive. Instead, it is important to address the fact that cellulose adhesion performs at its best when connected through hydrogen bonds ranging from the macro level to the nano level. Regarding this matter, it is obligatory to mention that for knowledge about the application of these bioadhesive materials, in terms of composition, structural design and interactions with surfaces, it is crucial to expose the basic information about the biochemical and mechanical principles that are associated with the process of biological adhesion.

Similarly, protein-based bioadhesives are also recognized as one of the most significant and prolific categories of macromoecules in cells that facilitate the creation of bonding among microorganisms. In another way, it can be said that correspondingly, each protein molecule can be imagined as a polymer composed of amino acids, which are known as tiny macromolecules that contain an amine group, a carboxylic acid group and a variable side chain [9].
