The Development of Eco-Friendly Biopolymers for Use in Tissue Engineering and Drug Delivery

Mahmud, Md. Zobair Al; Islam, Md. Didarul; Mobarak, Md Hosne

doi:https://doi.org/10.1155/2023/9270064

Journal of Nanomaterials

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Abstract Introduction Conclusion Data Availability Conflicts of Interest Authors’ Contributions References Copyright Related Articles

Review Article | Open Access

Volume 2023 | Article ID 9270064 | https://doi.org/10.1155/2023/9270064

The Development of Eco-Friendly Biopolymers for Use in Tissue Engineering and Drug Delivery

Md. Zobair Al Mahmud,¹Md. Didarul Islam,¹and Md Hosne Mobarak¹

Academic Editor: Dong Kee Yi

Received12 Jul 2023

Revised05 Aug 2023

Accepted14 Oct 2023

Published31 Oct 2023

Abstract

Tissue engineering and drug delivery have emerged as promising fields that hold the potential to revolutionize modern healthcare. The widespread use of synthetic polymers in these applications raises concerns about their environmental impact and biocompatibility. In response, researchers have shifted their focus toward the development of eco-friendly biopolymers as viable alternatives. This review paper aims to comprehensively analyze the progress made in the utilization of biopolymers for tissue engineering and drug delivery, with an emphasis on their ecological advantages and biomedical performance. The review begins by exploring the diverse sources of biopolymers, such as proteins, polysaccharides, and nucleic acids, derived from renewable resources, agricultural waste, etc. The discussion then delves into the unique properties of these biopolymers, including their biodegradability, nontoxic nature, and potential for controlled drug release. The incorporation of biopolymers in tissue engineering scaffolds is critically examined. The review also explores the role of biopolymers in the drug delivery systems, with a focus on nanoparticles, microparticles, hydrogels, and films. The capability of biopolymers to encapsulate and protect therapeutic agents, as well as their controlled release, is discussed in the context of targeted drug delivery and improved therapeutic outcomes. This paper highlights the challenges and future perspectives in the field of eco-friendly biopolymers for tissue engineering and drug delivery. Promising advancements in biofabrication techniques, nanotechnology, and personalized medicine are identified as key drivers for the rapid translation of these materials into the clinical applications. The development of eco-friendly biopolymers offers a sustainable and bio-safe alternative to the traditional synthetic polymers in tissue engineering and drug delivery. This comprehensive review underscores the crucial role of biopolymers in fostering advancements in regenerative medicine and therapeutic interventions while prioritizing environmental preservation and human health.

1. Introduction

Green biopolymers have emerged as a potential alternative in the fields of tissue engineering and medication delivery, providing ecologically friendly and sustainable solutions [1]. Because of the growing demand for biocompatible materials, the development of biopolymers generated from renewable resources has received a lot of attention. These green biopolymers are not only biocompatible, but also have favorable mechanical qualities, making them appropriate for a variety of biomedical applications [2]. Furthermore, their synthesis and processing procedures use environmentally friendly methods, reducing the environmental effect. The purpose of this paper is to investigate the synthesis of green biopolymers for tissue engineering and drug delivery applications, emphasizing their advantages over conventional synthetic polymers and emphasizing the potential of these sustainable biomaterials in advancing regenerative medicine and targeted drug delivery systems.

Tissue engineering has made considerable advances in recent years, with the goal of generating functional and biocompatible materials that can replicate the natural extracellular matrix (ECM) and assist tissue regeneration [3]. Traditional synthetic polymers, such as polyethylene glycol (PEG) and poly (lactic-co-glycolic acid) (PLGA), are widely utilized; nevertheless, their synthesis requires the use of nonrenewable resources and frequently results in the development of harmful byproducts [4]. Green biopolymers derived from natural sources, including polysaccharides like chitosan, cellulose, and alginate, as well as proteins such as collagen and silk fibroin, offer a sustainable alternative [5]. These biopolymers may be derived from plentiful and renewable sources such as plants, animals, and microbes, reducing dependency on fossil fuels and lowering carbon footprint.

Green biopolymer synthesis is a potential option for tissue engineering and drug delivery applications. Because of their long-term viability, high biocompatibility, and programable qualities, they are attractive candidates for producing functional biomaterials that stimulate tissue regeneration and allow controlled drug release. Furthermore, the environmentally friendly synthesis and processing procedures associated with green biopolymers help to reduce the ecological imprint of biomedical research and pave the way for a more sustainable future in regenerative medicine and tailored treatments [6]. Polymers should be altered to provide an acceptable amount of regeneration in order to replicate the behavior of a tissue. By utilizing synthetic polymers, various types of additives, and nanoparticles to create biocomposites, new functions may be added to the biopolymers [7, 8]. To imitate the architecture and characteristics of bone, hydroxyapatite has been introduced to biopolymer-based scaffolds [9, 10]. To induce stimulation and regulated medication release, magnetic nanoparticles have also been added to chitosan [11]. In order to create a scaffold that can imitate the behavior of the targeted tissue, it is important to understand the targeted tissue properties. Evidently, conductive substrates are favored for engineering brain tissue, but conductive elastomers would be a superior option for an engineering cardiac tissue [7]. The conductivity and mechanical characteristics of tissue are shown in Figure 1.

For example, brain is a soft tissue, whereas the bone is best known as a hard tissue. Biomaterials selection for such opposed tissues should be considered in terms of mechanical strength of biomaterials. From conductivity point of view, brain has conductivity similar to that of semiconducting materials. The chemistry of the utilized biomaterial should also be considered carefully, to make it able to resemble native extracellular matrix (ECM) needed for required level of tissue mimicking performance [12].

The primary tissue-specific regeneration processes that underlie the effectiveness of biopolymers in tissue engineering are also typically covered. To emphasize the performance window and other information related to functional biopolymers, biopolymers produced for various tissue scaffolds, such as neural, cardiac, skin, and bone, is individually examined. Biocomposites crafted from natural polymers are of particular concern, especially in the context of eco-friendly biopolymers used for tissue engineering and drug delivery.

2. Green Biopolymer Resources

Green biopolymers, which provide environmentally friendly substitutes for conventional petroleum-based plastics, are produced by a variety of plants and other natural sources [13]. Through processing, PLA and other biodegradable polymers may be made from maize [14]. To lessen dependency on fossil fuels, sugarcane is also used to produce biopolymers such poly hydroxyl alkanets (PHA) and bio-based polyethylene (PE) [15]. Chitin, a biopolymer with several uses in the domains of packaging and biomedicine, may be produced from the exoskeletons of crustaceans such as shrimp and crab, which is another noteworthy source [16]. A plentiful and renewable source of biopolymers is cellulose, an essential component of plant cell walls. It may be produced from materials like cellulose acetate and cellulose-based polymers as well as sources including wood pulp, cotton, hemp, and bamboo [17]. Due to their quick growth and low-resource needs, algae, and seaweed are gaining popularity as sustainable biopolymer sources. These marine creatures may be processed to produce biopolymers like agar, carrageenan, and alginate that are used in food packaging, medications, and biomedical equipment [18, 19]. In addition, some bacteria, such the strain Escherichia coli, may be genetically altered to make biopolymers like poly-3-hydroxybutyrate (PHB), which aids in the creation of bio-based plastics.

Figure 2 shows proteins, neutral polysaccharides, cationic polysaccharides, microbes, and plants are just a few of the many sources from which natural renewable biopolymers are produced. Proteins can be obtained from a variety of sources, including plant seeds, microbes, and animal byproducts [20]. Cell walls of plants and arthropod exoskeletons are both rich in neutral polysaccharides like cellulose and chitin [21]. These polysaccharides can be isolated and used in a variety of ways. On the other hand, cationic polysaccharides have positive charges because they include amino or ammonium groups [22]. They are derived from plants, microbes, and marine creatures and employed in the food, pharmaceutical, and cosmetic sectors [23]. Biopolymers with distinct characteristics can also be produced by microorganisms like bacteria and fungus [24]. For instance, several bacterial species generate bacterial cellulose, which is used in tissue engineering and wound treatments [25]. Table 1 indicates that biopolymers are formed from renewable sources, such as chitin, which is present in the exoskeletons of insects and crustaceans and is a precursor to chitosan. Plants have a lot of cellulose, which serves as structural support. Alginate is derived from seaweed and has gelling characteristics [26]. Plants use the starch they acquire from grains and tubers as a kind of energy storage and due to their biodegradability, biocompatibility, and nontoxicity, these biopolymers are suitable for a wide range of applications [27]. They are being used more often in a variety of industries, from biomedical gadgets to sustainable packaging, helping to create a greener and more ecologically friendly future.

3. Biopolymers Characterization Process

These characterization procedures are critical in understanding and optimizing the characteristics of biopolymers for use in a variety of sectors, including packaging, textiles, biomedical, and others. The process of determining the physical, chemical, and structural characteristics of biopolymers comprises a variety of methodologies and approaches. Fourier Transform Infrared Spectroscopy (FTIR) is a regularly used method that examines the molecular vibrations and functional groups present in the biopolymer, providing information on its chemical makeup [35]. The crystalline structure of biopolymers is studied using X-ray diffraction (XRD), which provides information on their molecular order and packing [36]. Scanning electron microscopy (SEM) and Rheology are used to examine the physical and structural properties of the biopolymers further [37]. Mechanical testing is important in the characterization of biopolymers which entails submitting biopolymer samples to various stresses and evaluating their responses in order to determine their mechanical characteristics [38]. Tensile testing, compression testing, bending testing, and shear testing are some popular mechanical testing methodologies for biopolymers. Tensile testing assesses the material’s response to stretching pressures, whereas compression testing assesses its response to the compressive forces. Bending testing evaluates the biopolymer’s resistance to flexural stress, whereas shear testing evaluates its resistance to forces applied parallel to its surface. These mechanical tests give useful information on the biopolymer’s strength, stiffness, elasticity, and other mechanical characteristics, which aids in characterization and understanding of its possible uses.

Table 2 clearly illustrates the origin of various polysaccharide sources by listing their structural characteristics. Polysaccharides have been extensively utilized in the production of nano and microparticles due to their unique properties. Chitosan, a derivative of chitin, is a widely studied polysaccharide known for its biocompatibility and biodegradability. It has been employed in the formulation of nanoparticles for drug delivery systems, gene therapy, and wound healing applications. Table 3 presents biocomposite films and their properties, alongside corresponding analytical methods employed for the characterization.

Analytical techniques are essential for identifying the properties of biocomposite. Mechanical characteristics are evaluated using tensile and flexural testing, and their thermal stability and degradation behavior are better understood through thermal analysis (DSC and TGA). The morphology and fiber-polymer interfacial bonding can be better understood by SEM. Using FTIR, chemical interactions inside the biocomposite are investigated. Tests for biodegradability determine how they affect the environment. Life cycle assessment (LCA), makes it possible to measure the ecological footprint.

4. Application

Biopolymers play a vital role in tissue engineering and drug delivery due to their biocompatibility, biodegradability, and versatility as shown in Figure 3. Biopolymers can be utilized as scaffolds in tissue engineering to facilitate cell development and tissue regeneration. In order to encourage cell adhesion, proliferation, and differentiation, they offer a three-dimensional framework that resembles the natural extracellular matrix. In controlled drug delivery systems, biopolymers also act as drug carriers, allowing therapeutic substances to release slowly over time. Their capacity to enclose and safeguard medications while enabling their focused distribution improves therapeutic effectiveness and reduces negative effects. Biopolymers have transformed medication delivery and tissue engineering, providing innovative approaches to personalized and regenerative healthcare. Figure 3 depicts the various applications of biopolymers.

4.1. Tissue Engineering

An interdisciplinary field of study called tissue engineering uses chemistry, material science, engineering, and medicine to replace and repair organs and tissues [71]. The three major components of tissue engineering methodologies are scaffold, differentiated, or undifferentiated cells, and biological signaling molecules like growth factors (GFs) [72]. Recent developments in a variety of biodegradable natural polymer hydrogels, such as those made of chitosan, hyaluronic acid, alginate, and agarose, as well as proteins (collagen, gelatin, fibroin, and fibrin), and polysaccharides (chitosan, fibroin, and fibrin), are detailed here. These natural biopolymers exhibit distinctive physicochemical characteristics that are rooted in their chemical structures. These characteristics specify the advantages and limitations of each hydrogel material for applications in cartilage tissue engineering, such as cell adhesion, scaffold degradation kinetics, and mechanical strength [73]. Alginate hydrogels are frequently utilized as scaffolds for neural tissue engineering, drug, protein/enzyme, and cell delivery, protein immobilization, bone, and cartilage tissue engineering, and protein immobilization [74–77]. A variety of alginate materials have been created to satisfy distinct application-specific criteria. Alginate and its derivatives’ chemistry, characteristics, and biological uses have recently been thoroughly reviewed in reviews [78].

Tissue engineering employs top–down methods, manipulating existing tissues, and bottom–up techniques, creating tissues from cells and biomaterials, to develop innovative regenerative therapies, addressing diverse medical challenges [79]. Top–down tissue engineering entails creating new tissue constructions by dissecting an existing tissue into smaller pieces first. These elements are altered and arranged into desired structures using biomaterials. Building tissues from single cells or cell aggregates that are seeded onto biomaterial scaffolds to promote tissue development and organization is the focus of bottom–up tissue engineering [80]. Figure 4 depicts the methods used to solve diverse tissue engineering difficulties and produce viable tissue constructions for regenerative medicine and organ replacement.

Here is a list of some important biopolymers used in tissue engineering:(1)Collagen: collagen is the most abundant protein in the ECM and is a critical component of various tissues, such as skin, bones, and cartilage. It provides structural support and promotes cell adhesion and migration. Collagen-based scaffolds are widely used in tissue engineering applications due to their excellent biocompatibility and biodegradability [82].(2)Hyaluronic acid (HA): HA is a natural polysaccharide found in the ECM of many tissues, including skin and cartilage. It possesses excellent water retention properties and contributes to tissue hydration and lubrication. HA-based hydrogels are used to create scaffolds for tissue engineering applications, especially in cartilage repair and wound healing [83].(3)Chitosan: chitosan is derived from chitin, a polysaccharide found in the exoskeletons of crustaceans. It has antimicrobial properties and promotes cell attachment and proliferation. Chitosan-based scaffolds are used in tissue engineering for applications like bone regeneration and wound healing [84].(4)Fibrin: fibrin is a protein involved in the blood clotting process and is commonly used as a scaffold material in tissue engineering. It can be easily cross-linked to form hydrogels, providing a three-dimensional environment for cell growth and tissue regeneration [85].(5)Silk fibroin: silk fibroin is derived from silk, a natural protein produced by silkworms. It has good mechanical properties and biocompatibility. Silk-based scaffolds are utilized in tissue engineering for various applications, including nerve regeneration and bone tissue engineering [86].(6)Alginate: alginate is a polysaccharide extracted from brown algae. It forms hydrogels in the presence of divalent cations, making it suitable for encapsulating cells and promoting tissue growth in various tissue engineering applications [87].

Table 4 list biopolymers that may be combined or used singly to make scaffolds, hydrogels, and other structures that offer the right conditions for cells to develop, differentiate, and regenerate tissues. Due to their biological relevance and capacity to direct tissue formation and repair, they have a great deal of potential for use in tissue engineering and regenerative medicine. However, to improve tissue engineering outcomes and solve the unique difficulties related to different tissue types, researchers are still investigating novel techniques and biopolymer combinations.

Bio-inks play a vital role in tissue engineering, serving as printable materials for 3D bio-printing. Alginate-based bio-inks offer biocompatibility and structural support. Gelatin-based bio-inks promote cell adhesion and proliferation. Fibrin-based bio-inks facilitate tissue regeneration with the natural extracellular matrix components. Chitosan-based bio-inks possess antimicrobial properties and promote tissue integration. Each bio-ink’s unique properties cater to diverse tissue engineering applications, from cartilage and bone to skin and vascular constructs.

4.2. Drug Delivery

Due to their distinctive qualities and possible uses, biopolymers have become recognized as promising materials in the field of medication delivery [99]. In terms of biocompatibility, biodegradability, and low immunogenicity, these naturally produced polymers—such as proteins, polysaccharides, and nucleic acids—offer significant benefits over synthetic polymers [100]. The pharmaceutical industry is very interested in their capacity to encapsulate and distribute therapeutic substances to specified target locations in a regulated manner.

A variety of medications, including small molecules, peptides, and proteins, can be encapsulated in biodegradable and biocompatible biopolymers that can be formed into nanoparticles or microparticles [101]. These particles can strengthen the drug’s stability and solubility while also preventing it from degrading, which will increase the drug’s therapeutic potency. Additionally, biopolymer-based nanoparticles’ surface characteristics can be changed to provide precise targeting to sick tissues or cells, increasing medication delivery effectiveness while minimizing side effects [102]. Biopolymers can be used to improve the stability and delivery of pharmaceuticals made from nucleic acids like DNA or RNA [103]. These biomacromolecules have a low-cellular uptake and are extremely susceptible to enzymatic breakdown. Nucleic acids can be better protected from enzymatic degradation and given to target cells more easily by complexing with biopolymers. Gene therapy and vaccines based on nucleic acids may be made possible by biopolymer-based formulations that preserve nucleic acids and enhance their intracellular delivery [100].

According to Tables 5–7 biopolymers are great candidates for the creation of efficient and targeted drug delivery systems because of their biocompatibility, biodegradability, and ability to encapsulate and release therapeutic compounds in a controlled manner. The topic of medication delivery has great potential for the biopolymers. Further research and development in this field will enable the use of biopolymers in improving medicine delivery and revolutionizing the pharmaceutical business, ultimately benefiting patients throughout the world. Current research on the use of cellulose and its derivatives in medication administration is summarized in Table 5.

By modifying cellulose through chemical derivatization, its properties can be tailored to achieve controlled drug release, improved stability, and targeted delivery, making it a promising candidate for efficient and safe drug delivery systems in the pharmaceutical industry [113]. Table 6 outlines current research on chitosan’s potential in drug delivery applications.

Chitosan, a natural biopolymer derived from chitin, exhibits biocompatibility, biodegradability, and low toxicity, making it an ideal candidate for encapsulating drugs and targeting specific sites in the body. Its unique properties offer potential advancements in targeted therapies and sustained drug release systems [122]. Table 7 summarizes current studies on gelatin’s usage in drug delivery applications.

Gelatin finds versatile applications in drug delivery, serving as a biocompatible and biodegradable material. Its encapsulation properties aid in controlled release of pharmaceuticals, enhancing drug stability and targeting specific sites. Additionally, it enables the creation of various drug carriers like nanoparticles, microparticles, and hydrogels, fostering advancements in personalized medicine [131].

5. Future Prospects and Challenges

Biopolymers have bright futures since they provide a sustainable and eco-friendly alternative to synthetic polymers that are often used in the industry [113]. Biopolymers, which are made from renewable resources including plants, microorganisms, and algae, provide a solution to the difficulties of plastic pollution and the depletion of fossil fuels. Applications for biopolymers include the packaging, textiles, and automotive, building, and biomedical sectors [114]. They are a desirable alternative for lowering waste and carbon impact because of their biodegradability and compatibility with the current manufacturing techniques. Additionally, biopolymers have the ability to display distinctive qualities and functions, enabling the creation of novel materials with improved performance. For biopolymers to be widely used, a number of issues must be resolved. These include enhancing its cost-effectiveness, scalability of production, mechanical strength, and thermal stability. This review paper has highlighted the significant progress made in this field, showcasing the potential of biopolymers as a promising alternative to conventional synthetic materials. Looking ahead, several future prospects can be envisioned to drive this research area toward greater success. The ability to tailor the biodegradability of biopolymers opens up exciting possibilities for tissue engineering and drug delivery. By controlling the degradation rates, researchers can develop biopolymer-based scaffolds that provide mechanical support during tissue regeneration and gradually degrade as new tissue forms, eliminating the need for invasive removal procedures. The incorporation of bioactive molecules, such as growth factors and cytokines, into biopolymer matrices can enhance tissue regeneration and drug delivery applications. Future prospects include optimizing the release kinetics of these bioactive molecules to mimic the natural healing process, thereby accelerating tissue repair and reducing the need for repeated administrations. The primary challenges lies in establishing standardized production processes for biopolymer-based materials. Large-scale manufacturing with consistent quality is essential for their widespread adoption in tissue engineering and drug delivery, and this requires addressing variability in source materials, extraction techniques, and processing methods. While biopolymers offer inherent biocompatibility, some variations may still trigger immune responses in certain individuals. Understanding and minimizing immunogenicity is critical to ensure successful clinical translation. Additionally, achieving optimal biodegradation kinetics remains challenging, as it varies with tissue type and environmental conditions. As with any emerging technology, the cost-effectiveness of biopolymer-based solutions will influence their widespread adoption. Developing efficient and economical production methods and scaling up manufacturing processes are vital to make these materials accessible to a broader population. Despite the positive outlook for biopolymers, these issues must be resolved if they are to reach their full potential as a sustainable alternative to synthetic polymers [115]. The development of eco-friendly biopolymers for tissue engineering and drug delivery is an exciting area of research with enormous potential for transforming biomedical applications. With continued innovation and concerted efforts to overcome existing challenges, these biopolymers can pave the way for sustainable, personalized, and highly effective medical treatments in the future. Embracing these prospects and addressing the challenges will drive this field toward a greener and healthier future.

6. Conclusion

The development of eco-friendly biopolymers for use in tissue engineering and drug delivery holds tremendous promise as a sustainable and innovative approach to revolutionize the biomedical field. This comprehensive review highlights the remarkable progress achieved in recent years, emphasizing the significant advantages that biopolymers offer over traditional synthetic polymers. The utilization of natural, renewable resources for biopolymer production not only reduces the dependence on fossil fuels but also mitigates the environmental impact associated with nonbiodegradable materials. The biocompatibility and biodegradability of these biopolymers make them ideal candidates for a wide range of applications, including tissue engineering, drug delivery, and regenerative medicine. One of the key takeaways from this review is the vast array of sources available for biopolymer extraction, such as polysaccharides (e.g., chitosan, cellulose, and starch), proteins (e.g., collagen, gelatin, and silk fibroin), and nucleic acids (e.g., DNA and RNA). These diverse sources present researchers with an ever-expanding toolkit, allowing for tailoring biopolymers with specific properties to meet the unique requirements of different applications. Furthermore, advances in the processing techniques, such as electrospinning, 3D bioprinting, and microfluidics, have facilitated the fabrication of intricate structures, mimicking native tissues and organs more accurately. This has paved the way for the development of patient-specific implants and drug delivery systems that enhance the therapeutic efficacy while minimizing adverse effects.

However, despite these remarkable achievements, several challenges still lie ahead in the field of eco-friendly biopolymers. Standardization of production methods and quality control protocols remains a priority to ensure consistency and reproducibility across different biopolymer types. Additionally, the long-term stability and degradation rates of these materials need further investigation to optimize their performance in various biomedical applications. Addressing these challenges will not only enhance the reliability of biopolymer-based products but also facilitate their regulatory approval and widespread clinical adoption. The integration of biopolymers with advanced biomaterials, such as nanoparticles and hydrogels, presents an exciting avenue for the next generation of tissue engineering and drug delivery systems. These hybrid approaches could potentially offer enhanced therapeutic capabilities, targeted drug release, and better control over cellular responses. Furthermore, combining biopolymers with bioactive molecules, growth factors, or stem cells can unlock new possibilities in tissue regeneration, organ transplantation, and personalized medicine. As the field continues to evolve, collaboration between researchers, clinicians, and industry stakeholders will be crucial to propel eco-friendly biopolymer technologies into the mainstream. Government support, funding initiatives, and public awareness campaigns will also play pivotal roles in driving the adoption of sustainable biomaterials in the healthcare sector. By capitalizing on interdisciplinary expertise and embracing innovative approaches, we can accelerate the translation of biopolymer-based advancements from the laboratory to the clinical practice. In summary, this review highlights the immense potential of eco-friendly biopolymers in tissue engineering and drug delivery, emphasizing their sustainable nature, biocompatibility, and versatility. The strides made in biopolymer research have paved the way for a greener, more ethical approach to biomedical applications, shaping the future of regenerative medicine and patient care. With continued dedication, research, and collaborative efforts, eco-friendly biopolymers are poised to revolutionize the biomedical landscape and usher in a new era of therapeutic solutions that are not only effective but also environmentally responsible.

Data Availability

The data used in this review article are derived from publicly available scientific literature and research papers obtained from reputable databases such as PubMed, Scopus, and Web of Science. The specific references for the data used in this review are cited appropriately in the reference list. No primary data or experimental results were generated for this study.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Md. Zobair Al Mahmud specializes in writing, while Md. Didarul Islam is proficient in data management and revision. Meanwhile, Md Hosne Mobarak excels in conceptualization and revision.

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Copyright © 2023 Md. Zobair Al Mahmud et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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