General Trends on Biomaterials Applications: Advantages and Limitations

Abstract

The field of biomaterials has witnessed significant advancements in recent years, with increasing applications in various medical disciplines. This book chapter provides an overview of the trends in biomaterials applications, highlighting their advantages and limitations. Biomaterials play a critical role in improving patient outcomes, enabling the development of innovative medical devices, and enhancing the quality of life. They find extensive use in orthopedics, esthetic surgery, ophthalmology, maxillofacial surgery, cardiology, urology, neurology, and other medical specialties. While biomaterials offer numerous benefits, their selection and design depend on specific medical applications. Biocompatibility, adequate mechanical properties, physical and chemical characteristics, wear resistance, corrosion resistance, and osseointegration are important considerations. However, the complexity of the biological environment and the lack of detailed knowledge about in vivo conditions pose challenges. The success of an implant replacement relies on the tissue-material interface, which varies based on the desired outcome. Hemocompatible behavior is necessary for implants in contact with blood, whereas osseointegrated implants require a strong interaction for high adhesion force. This chapter also discusses the limitations of biomaterials, including immune reactions, limited biocompatibility, durability issues, interactions with the surrounding environment, lack of regeneration, high costs, and design constraints. It emphasizes the importance of ongoing research and development to overcome these limitations and advance the field of biomaterials.

1. Introduction

Biomaterials are constantly used in the medical field and can be defined as “materials that present new properties that make them suitable to come into direct contact with living tissue without causing an immune rejection or an adverse reaction” [1]. It should be mentioned that the prefix “bio” of biomaterials refers to “biocompatible,” rather than “biological” or “biomedical,” as is often misinterpreted [2, 3, 4, 5].

Biomaterials have been utilized in various forms throughout antiquity, demonstrating the ingenuity and resourcefulness of ancient civilizations. Although the concept of biomaterials as we understand them today was not fully developed, ancient societies intuitively utilized natural materials with desirable properties for medical purposes. In ancient Egypt, linen and papyrus were employed as bandages and wound dressings, providing protection and aiding in healing [6, 7]. Natural resins like myrrh and frankincense, known for their antimicrobial properties, were incorporated into ointments and balms. In ancient Greece, honey was used for its antibacterial and anti-inflammatory effects, while olive oil served as a moisturizer and enhancer of medicinal herbs. Traditional Chinese medicine relied on biomaterials derived from plants, animals, and minerals. Herbal remedies with ginseng, aloe vera, and pearl powder promoted healing and rejuvenation. Natural substances like shells, bones, and stones were used for their mechanical properties in bone setting and acupuncture. These early practices laid the foundation for the development of modern biomaterials in medicine [8, 9, 10, 11].

The first generation of biomaterials emerged in the 1950s and 1960s and primarily consisted of industrial materials that were not specifically developed for medical use. These biomaterials were selected based on their physical properties relevant to the intended clinical application and their bioinert nature, meaning they elicited minimal response in host tissues and were considered biocompatible. Common materials included polymers, metals, and ceramics. The primary goal of first-generation biomaterials was to achieve an appropriate combination of functional properties that matched the replaced tissue without eliciting deleterious host responses. Examples of first-generation biomaterials include pyrolytic carbon, initially developed for coating nuclear fuel particles, and later used in modified forms to coat mechanical heart valve components [12, 13, 14].

The second generation of biomaterials evolved from the first generation and aimed to induce specific therapeutic effects by causing controlled reactions with the surrounding tissues. These bioactive materials were designed to interact with the host tissue to achieve desired outcomes [14, 15, 16]. Examples of second-generation biomaterials include bioactive glasses and ceramics used in orthopedic and dental surgeries for localized controlled drug release applications. Another example is the HeartMate® left ventricular assist device, which features a textured polyurethane surface that promotes a controlled thrombotic reaction to minimize the risk of blood clotting. Drug-eluting endovascular stents, which limit restenosis (blood vessel closure) after balloon angioplasty, are also considered second-generation biomaterials [17, 18, 19].

Additionally, the second generation saw the development of resorbable biomaterials that could be degraded over time. These biomaterials had tailored degradation rates, allowing them to be absorbed by the host tissue and eliminating the need for long-term foreign materials. A well-known example is the use of biodegradable sutures composed of polyglycolic acid (PGA) since the 1960s. Ongoing research focuses on finding biodegradable polymers with properties such as strength, flexibility, tissue-friendly composition, and degradation rates suitable for specific applications. Novel properties like shape memory and programmable and interactive surfaces controlling the cellular microenvironment are also being investigated within the realm of second-generation biomaterials [20].

Biomaterials play an essential role in the human body by serving as artificial substitutes or implants that interact with living tissues, organs, and bodily fluids. They contribute to various medical treatments, therapies, and interventions, improving patient health and quality of life. In Table 1. are the essential roles of biomaterials in the human body [21, 22, 23].

Application	Description	Example
Medical Implants	Biomaterials are used as implants to replace or support damaged or dysfunctional body parts	joint replacements, heart valves, pacemakers, and vascular stents, restoring cardiovascular functionality
Tissue Engineering and Regenerative Medicine	Play an important role in tissue engineering and regenerative medicine. They provide scaffolds or matrices to support the growth and regeneration of tissues and organs. These biomaterial scaffolds mimic the extracellular environment and guide cell growth, leading to the formation of new tissue	skin grafts, bone grafts, and artificial organs
Drug Delivery Systems	Are used as carriers or vehicles for controlled drug delivery. They can be engineered to release drugs or therapeutic agents in a controlled manner, targeting specific tissues or cells. This approach improves drug efficacy, reduces side effects, and enhances patient compliance	Implants, nanoparticles, hydrogels, or microparticles
Diagnostic and Therapeutic Devices	Are integral to the development of diagnostic and therapeutic devices. Biosensors and biochips utilize biomaterials to detect and analyze biological samples for diagnostic purposes	Catheters, prosthetics, and surgical instruments to ensure compatibility and minimize adverse reactions
Wound Healing and Dressings	Are employed in wound healing and dressings. They can create a conducive environment for wound healing by controlling moisture levels, promoting tissue regeneration, and preventing infection	wound healing and dressings
Dental Materials	Are extensively used in dentistry for various applications. Tooth-colored composites and ceramics restore damaged teeth, mimicking natural tooth structure and appearance. Dental adhesives and cements facilitate the bonding of restorative materials to tooth structures	Orthodontic braces and aligners to correct dental misalignments
Surgical Tools and Equipment	Play a role in surgical tools and equipment. Instruments made from biocompatible materials ensure compatibility with the human body during surgical procedures	Implants or sutures that eventually degrade and are absorbed by the body
Research and Development	Are vital in research and development of new medical technologies and treatments. They enable in vitro studies and preclinical testing of medical devices, drug delivery systems, and tissue engineering approaches	New medical technologies and treatments

Table 1.

Biomaterials roles in the human body [21, 22, 23, 24].

Overall, biomaterials contribute significantly to modern medicine and healthcare. They enable the repair, replacement, and regeneration of damaged tissues and organs, facilitate drug delivery, improve diagnostic capabilities, and support surgical interventions. By harnessing the unique properties of biomaterials, researchers and medical professionals continue to advance treatments and interventions, ultimately improving patient outcomes and well-being.

The growth and success of the field of biomaterials are evident, as proven by multiple statistics. Researchers are continuously contributing to this field to continue its growth and strengthen its significance for medicine and biology. They address several impediments that appear from patient to patient, contributing significantly to their improvement [8].

2. Classification of materials used for medical applications

The role of biomaterials in the medical field has undergone substantial transformations in response to advances in science and technology. The ever-evolving healthcare landscape and the growing demands of medical practice have been pivotal drivers behind the continuous developments in the field of biomaterials and their diverse applications.

Biomaterials are typically categorized based on their functionality within the human body and their unique material properties [6]. To begin with, one approach to classification is based on their application at various levels of the human body. At the systemic level, biomaterials are used to restore and repair vital systems, such as the skeletal system, where joint replacements and bone plates have become indispensable. On the organ level, we witness remarkable advancements, with artificial heart valves, total valve replacements, and cardiac pacemakers offering life-changing solutions for heart-related ailments. Additionally, the treatment of specific body parts sees biomaterials like artificial hip joints and kidney dialysis machines replacing or aiding damaged or diseased organs, while materials such as screws, sutures, and bone plates play an important role in wound healing.

Another significant classification of biomaterials revolves around their material properties, primarily dividing them into four broad categories: metals, composites, ceramics, and polymers (Figure 1). The extensive range of biomaterial options offers practitioners a diverse selection to match specific treatment requirements. For instance, chemically inert metals are chosen for their high electroconductivity and durability, making them suitable for use as electrodes in artificial organs and for long-term restoration of bodily functions. Conversely, biodegradable materials like sutures serve as temporary frameworks, facilitating tissue regeneration in patients who require it.

1. Metals are a class of materials characterized by their high electrical conductivity, malleability, ductility, and typically high strength. They consist of metallic elements and often exhibit metallic bonding, where electrons are delocalized and shared among atoms. Metals are commonly used in engineering and biomaterial applications due to their mechanical properties and biocompatibility. Some examples of metals used in biomaterials include titanium, stainless steel, cobalt-chromium alloys, and tantalum. Metals are often utilized for load-bearing applications such as orthopedic implants, dental implants, and cardiovascular stents [25, 26, 27].

2. Composites are materials composed of two or more distinct components, such as fibers, particles, or flakes, embedded in a matrix material. The combination of different materials in a composite allows for synergistic properties that are superior to those of the individual components alone. Composites can be engineered to have specific mechanical, electrical, or thermal properties. In biomaterials, composite structures are commonly formed by reinforcing a polymer matrix with fibers or particles made of materials such as carbon fiber, glass fiber, or ceramic particles. The matrix material holds the reinforcement together and transfers loads. Composites find applications in various fields, including aerospace, automotive, and biomedical engineering [28].

3. Ceramics are inorganic, non-metallic materials that are typically composed of metallic and non-metallic elements. They are known for their high melting points, hardness, stiffness, and excellent thermal and chemical stability. Ceramics can be crystalline or amorphous in structure. In the context of biomaterials, ceramics such as alumina, zirconia, and hydroxyapatite are used for their biocompatibility, wear resistance, and ability to bond with bone. Ceramic biomaterials are commonly employed in orthopedic implants, dental implants, and coatings for medical devices [29].

4. Polymers are large molecules composed of repeating subunits called monomers. They have long chains or networks of interconnected monomers, which give them unique properties. Polymers can be natural or synthetic. Natural polymers, such as collagen and elastin, are found in living organisms. Synthetic polymers, like polyethylene, polyurethane, and silicone, are widely used in biomedical applications. Polymers are known for their versatility, ease of processing, lightweight nature, and tunable properties. They can be tailored to have different mechanical, chemical, and biological characteristics, making them suitable for a wide range of biomaterial applications, including tissue engineering scaffolds, drug delivery systems, and medical device coatings [30].

Figure 1.

Classification of biomaterials.

It is important to note that the advantages and disadvantages mentioned above are general and can vary depending on the specific composition, processing techniques, and intended application of the biomaterials. The selection of biomaterials for a particular application should consider the specific requirements, such as mechanical properties, biocompatibility, degradation rate, and the desired interaction with host tissues [31].

The different classes of biomaterials exhibit distinct advantages and disadvantages, which play a defining role in their selection. Figure 2 provides an overview of the classification of biomaterials in medical applications, organized according to organs, systems, and other body parts. When choosing a biomaterial for a specific application, it is crucial to consider the material’s inherent properties, including corrosion resistance, biocompatibility, mechanical and metallurgical properties, as well as its performance during processing and use, cost, and availability. These factors directly influence the suitability of a material for a given application [32, 33, 34, 35, 36, 37, 38, 39].

Figure 2.

Few advantages and disadvantages of using different classes of biomaterials.

3. Biomaterials advantages and limitations

For medical applications, the design and material choice are vital and are based on the unique requirements of the application. It is important to take into account a few key factors when it comes to metal implants in order to guarantee their security and continued use without rejection. These characteristics include, but are not limited to:

1. Excellent biocompatibility: Biocompatibility is a fundamental requirement for any implant material. It refers to the ability of the material to interact with the biological system without causing adverse reactions or toxicity. A metal implant should be non-toxic and well-tolerated by the body to minimize the risk of inflammation, rejection, or other complications.

2. High corrosion resistance: Metal implants are exposed to physiological environments within the body, which can be corrosive. Therefore, it is crucial for the selected metal to possess high corrosion resistance. This ensures that the implant remains structurally stable and maintains its mechanical integrity over time, avoiding the release of potentially harmful metal ions or degradation products.

3. Adequate mechanical properties: Metal implants must possess adequate mechanical properties to withstand the physiological loads and stresses they will experience. These properties include strength, toughness, and fatigue resistance. Sufficient mechanical strength is essential to prevent implant failure or deformation under normal physiological conditions.

4. Wear resistance: Metal implants, particularly those involved in articulating joints, should exhibit good wear resistance. This helps to minimize the generation of wear particles and the associated inflammatory response, ensuring long-term performance and reducing the risk of complications.

5. Osseointegration: In the case of bone prostheses, such as hip or knee implants, osseointegration is a critical characteristic. It refers to the ability of the implant to integrate and form a stable bond with the surrounding bone tissue. This promotes long-term fixation and stability of the implant, allowing for efficient load transfer and improved patient mobility.

In addition to these characteristics, other factors, such as the material’s fabrication process, surface properties, and sterilization methods, also play a significant role in the design and selection of metal implants for specific medical applications. Each of these factors should be carefully evaluated and optimized to ensure the safety, efficacy, and long-term success of the implant in the intended patient population [40, 41, 42, 43, 44, 45].

By considering these essential characteristics and incorporating them into the design and selection process, engineers and medical professionals can ensure that metal implants meet the specific requirements of the medical application and contribute to improved patient outcomes and quality of life.

Each of the material classes has its own distinct properties and characteristics, making them suitable for specific applications in the field of biomaterials. The choice of material depends on factors such as mechanical requirements, biocompatibility, degradation properties, and the desired interaction with host tissues. Table 2 highlights some advantages and disadvantages of all classes [3, 17].

Class	Advantages	Disadvantages
Metals and alloys	High strength and mechanical properties, suitable for load-bearing applications. Good corrosion resistance. Compatible with imaging techniques like X-rays.	May cause stress shielding, where the implant absorbs stress instead of the surrounding bone, leading to bone loss. Limited ability to promote tissue regeneration.
Composites	Tailorable mechanical properties, combining the strengths of different materials. Can mimic the properties of natural tissues. Improved biocompatibility and ability to promote tissue regeneration compared to metals.	Complex fabrication processes. Potential for delamination or interface failure between the matrix and reinforcement. Limited availability of biocompatible composite materials.
Ceramics	Excellent biocompatibility. High strength and hardness. Chemical stability and resistance to wear. Capable of promoting bone regeneration.	Brittle nature, making them susceptible to fracture. Poor toughness and low tensile strength. Difficulty in achieving strong bonding with surrounding tissues.
Polymers	Versatility and ease of fabrication. Can be tailored to mimic the properties of natural tissues. Generally lightweight and flexible. Some polymers exhibit good biocompatibility and promote tissue integration.	Lower mechanical strength compared to metals and ceramics. Limited resistance to wear and degradation. Potential for leaching of chemicals or degradation byproducts. May cause inflammation or immune reactions in some cases.

Table 2.

Biomaterials roles in the human body.

There are numerous benefits to using metals and alloys as biomaterials. They are ideal for load-bearing applications such as orthopedic devices and implants because they have outstanding mechanical qualities such as high strength, toughness, and ductility. Many metals and alloys also have a natural resistance to corrosion, which helps them tolerate extreme physiological conditions and ensures their longevity and long-lasting performance in biomedical applications. Certain metals and alloys, including titanium and stainless steel, exhibit strong biocompatibility and are well-tolerated by the body, making it easier for implants used in orthopedics and dentistry to integrate with surrounding tissues and promote osseointegration. Additionally, the properties of metals and alloys can be precisely engineered through careful alterations to their chemical makeup and heat treatment processes, enabling customization to satisfy particular application needs.

Metals and alloys, while offering numerous advantages as biomaterials, also have certain limitations. One limitation is their relatively high density compared to other biomaterials, which can pose challenges in weight-sensitive applications like implants and prosthetics. Additionally, despite their inherent corrosion resistance, metals are still susceptible to wear and corrosion, especially in load-bearing scenarios, necessitating the use of protective coatings or regular monitoring for optimal long-term performance. Another limitation is the potential for allergenic reactions or hypersensitivity to specific metals or alloy components, such as nickel or cobalt, which may restrict their use in certain individuals with sensitivities [46, 47, 48, 49].

Composites possess several advantages as biomaterials:

• Tailored Properties: Composites allow for the combination of different materials, such as fibers or particles embedded in a matrix, enabling the attainment of specific mechanical, electrical, or thermal properties. This customization facilitates optimization for diverse applications.

• High Strength-to-Weight Ratio: Composites offer the advantage of high strength combined with low weight. This characteristic is particularly valuable in applications that require lightweight yet robust materials, including aerospace engineering or orthopedic implants.

• Improved Fatigue Resistance: Composites exhibit superior fatigue resistance compared to conventional materials. This attribute renders them well-suited for dynamic load-bearing applications, such as bone fracture fixation or sports equipment.

However, it is important to note that composites also have some limitations, including potential delamination between different material layers, difficulty in recycling due to material heterogeneity, and complexity in fabrication and processing. These limitations need to be carefully considered and addressed in order to fully harness the benefits of composite biomaterials [50, 51, 52, 53].

Ceramics are a class of biomaterials that offer numerous advantages for medical applications:

• Biocompatibility: Ceramics such as alumina, zirconia, and bioactive glasses exhibit excellent biocompatibility, meaning they are well-tolerated by the body and do not cause adverse reactions. This makes them suitable for various medical applications.

• High strength and hardness: Ceramics possess exceptional mechanical properties, including high strength and hardness. They can withstand substantial loads and provide structural support in applications such as dental implants and load-bearing joint replacements.

• Wear resistance: Ceramics exhibit low wear rates, making them suitable for articulating surfaces in joints. Their wear resistance helps to minimize the generation of wear debris, reducing the risk of inflammation and implant failure.

• Corrosion resistance: Many ceramics are highly resistant to corrosion, making them suitable for implantation in corrosive physiological environments. They can maintain their structural integrity and prevent the release of potentially harmful ions.

• Tailorable surface properties: Ceramics can be engineered with specific surface characteristics to enhance tissue integration and osseointegration. Surface modifications, such as coatings or roughening, can promote cell adhesion and accelerate the healing process.

Limitations/drawbacks of Ceramics:

• Brittle behavior: Ceramics are inherently brittle materials, meaning they have low fracture toughness and are prone to cracking under tension or impact. This limits their use in applications where high tensile or impact forces are expected.

• Difficulty in processing and shaping: Ceramics often require complex and specialized processing techniques such as sintering, which can be time-consuming and expensive. Additionally, their brittleness makes shaping and machining challenging.

• Lack of resorbability: Unlike certain biomaterials, such as biodegradable polymers, most ceramics are not resorbable by the body. They are intended for long-term use and may require surgical removal if replacement is necessary.

• Poor electrical conductivity: Ceramics have low electrical conductivity, which can be a limitation in certain applications where electrical stimulation or conductivity is required.

• Variability in properties: The properties of ceramics can vary based on factors such as composition, processing, and manufacturing techniques. This variability requires careful quality control and testing to ensure consistent and reliable performance [53, 54].

Polymers offer a wide range of advantages as biomaterials:

• Their versatility allows for a wide range of chemical compositions and the ability to engineer polymers with specific mechanical properties, such as flexibility or stiffness. This makes them highly adaptable for various medical applications, including drug delivery systems, wound dressings, and tissue scaffolds.

• Biocompatibility: Many polymers have excellent biocompatibility, meaning they are well-tolerated by the body and have minimal adverse reactions. They can be designed to closely mimic natural tissues, promoting cell adhesion, proliferation, and tissue regeneration.

• Ease of processing: Polymers are generally easier to process than other biomaterials. They can be molded, extruded, or fabricated into complex shapes using techniques like injection molding or 3D printing. This allows for efficient and cost-effective manufacturing of medical devices and implants.

• Tailorable degradation: Polymers can be designed to degrade at specific rates, allowing for controlled release of drugs or gradual integration with surrounding tissues. This enables precise modulation of the healing process and avoids the need for additional implant removal surgeries.

However, polymers also have certain limitations to consider:

• Mechanical strength: While polymers offer flexibility, they may have lower mechanical strength compared to metals or ceramics. This can limit their use in load-bearing applications or require reinforcement strategies.

• Degradation products: Some polymers may release degradation byproducts during breakdown, which can cause inflammation or tissue response. Careful selection of biocompatible polymers and a thorough understanding of their degradation mechanisms are crucial to minimize these effects [55, 56, 57, 58].

Despite these limitations, polymers remain an important class of biomaterials due to their versatility, biocompatibility, ease of processing, and tailorable degradation properties. Ongoing research and development efforts aim to address the limitations and further enhance the performance and applicability of polymer-based biomaterials in various medical fields.

It is important to address these limitations through advanced manufacturing techniques, process optimization, and thorough design analysis to fully exploit the potential of composites in various biomedical applications.

4. Applications of biomaterials in medicine

Biomaterials play a significant and multifaceted role in numerous fields, spanning orthopedics, esthetic surgery, ophthalmology, maxillofacial surgery, cardiology, urology, neurology, and practically all medical specialties encompassing over 400 distinct products. In the realm of medical sciences, biomaterials hold significant importance in the fabrication of dental devices, implants, prostheses, and tissue scaffolds [59, 60, 61]. These materials enable advancements in healthcare by providing solutions for various clinical needs, such as restoring mobility, improving esthetics, enhancing vision, repairing facial structures, treating cardiovascular conditions, addressing urological disorders, and facilitating neurological interventions. The broad utilization of biomaterials across diverse medical specialties underscores their indispensable role in enhancing patient care, promoting medical innovation, and improving overall quality of life.

Biomaterials have a vital role in diverse medical applications spanning across various classes:

4.1 Metals and alloys

• Orthopedics: The use of titanium alloys in the manufacturing of hip and knee replacements has significantly improved the outcomes of these surgeries by providing durable and biocompatible solutions for joint replacement. A notable example is the development of the Ti-6Al-4 V alloy, widely used in orthopedic implants due to its excellent mechanical properties and good biocompatibility [62, 63].

• Cardiology: Cobalt-chromium alloys have been pivotal in the advancement of coronary stents, enhancing the treatment of coronary artery disease. The L605 alloy, for example, is utilized for its superior strength and corrosion resistance, which are critical for maintaining blood vessel patency post-angioplasty [64].

4.2 Composites

• Dental: Dental composite materials have revolutionized esthetic dentistry, providing tooth-colored fillings that blend seamlessly with the natural tooth structure. A study by Maran et al. [65] highlights the use of nano-composite resins for fillings, which offer improved esthetics and strength compared to traditional materials.

• Sports medicine: Carbon fiber-reinforced polymers are utilized in the fabrication of custom orthotic devices for athletes, combining lightweight properties with high strength. The application of these composites in sports medicine allows for enhanced performance and injury prevention [66].

4.3 Ceramics

• Dental implants: Zirconia has become a material of choice for dental implants due to its excellent esthetic properties and biocompatibility. The use of zirconia implants in anterior tooth replacement has been documented for its superior esthetic outcomes and long-term success [53].

• Bone tissue engineering: Porous bioceramics, such as hydroxyapatite and tricalcium phosphate, are used in bone grafting procedures to support bone regeneration and healing. These materials provide a scaffold for bone ingrowth, as evidenced by their application in the repair of critical-size bone defects [67].

4.4 Polymers

• Drug delivery: Biodegradable polymers like PLGA (poly(lactic-co-glycolic acid)) are used in the development of controlled drug delivery systems, enabling targeted therapy with minimal side effects. The use of PLGA nanoparticles for the delivery of cancer therapeutics has shown promising results in reducing tumor growth [68].

• Tissue engineering: Polyethylene glycol (PEG)-based hydrogels are widely used in tissue engineering as scaffolds for cell culture and tissue regeneration. Their application in the development of engineered skin tissue for burn victims has demonstrated significant advances in wound healing and skin restoration [69].

Figure 3 provides a visual representation of various notable applications in medicine where biomaterials are utilized.

Figure 3.

Various representative applications in medicine.

Biomaterials include a wide range of materials other than metals because of the many requirements and applications in medicine. Based on their specific qualities and features, each class of biomaterials has advantages of its own. These biomaterials, which include composites, ceramics, and polymers, were created expressly to address the demands of various medical applications. They offer specialized answers for issues including mechanical strength, biocompatibility, flexibility, and controlled release, advancing medical therapies and improving patient care across a range of medical specializations. As a result, these non-metallic biomaterials continue to be essential for increasing the scope of medical interventions and raising the standard of care in general.

5. Characteristics and tissue interaction factors

The design and selection of biomaterials are contingent upon the specific medical application at hand. In order to excel in the biomedical field over an extended period without eliciting immune rejection (as illustrated in Figure 4), biomaterials must possess distinctive characteristics. These characteristics, which contribute to their efficacy, include biocompatibility, appropriate mechanical properties, suitable physical and chemical properties, adequate wear resistance, corrosion resistance, and the ability to promote osseointegration [70]. By fulfilling these criteria, biomaterials can meet the demanding requirements of diverse medical applications, ensuring compatibility with the human body, longevity of performance, and successful integration into the physiological environment.

Figure 4.

Schematic demonstration of biomaterial design requirements.

There are two relative quantitative aspects that distinguish the interactions of biomaterials with the biological environment and create the need for independent study of host and material responses:

1. Specific requirements – the biological environment, especially the internal environment of living systems, is very aggressive; it is an environment with intense and complex chemical activity combined with a wide spectrum, variable depending on some combined mechanical stresses.

2. Stable conditions – despite the aggressive aspects, the biological environment presents an extraordinary constant of both the physical conditions and the composition. There are complex control systems that ensure this constant. Therefore, deviations from the stable conditions due to the presence of the material can cause corresponding responses [71].

The aggressive aspects of the biological environment can be understood if we examine the differences between the internal and external conditions of living systems.

Regardless of the views on the development and origin of biological systems, everyone is impressed by their complexity. They perform their functions by accidentally excluding materials that are not needed, or that harm their function in individual processes. Rejection phenomena occur that act to exclude all materials that are toxic or not part of the body. Moreover, the system interacts both locally and regionally or globally. Therefore, a constant aspect of the biological environment is that the introduction of a foreign material will cause a host response, which may have local or systemic consequences [72].

Defining the precise biological environment in which a device or material fulfills a specific function is a challenging task. This challenge stems from the limited understanding of the intricate in vivo conditions and the local variations that can arise during the complex processes involved in maintaining homeostasis, which are essential for sustaining life. The intricate nature of biological systems and the dynamic interplay of various factors make it difficult to comprehensively characterize and predict the exact conditions under which a device or material operates within the body. This highlights the need for ongoing research and a deepening understanding of the complex biological processes to enhance our knowledge and enable more accurate assessments of the performance and functionality of biomedical devices and materials.

Also, there is some ambiguity in defining the region at the interface where the biological environment couples with a material. Implants in isolated body regions can interact with the rest of the system through ion and fluid diffusion, blood circulation, and lymph drainage. Even defining the absolute volume of material communicating with an implant can be difficult. The materials must be tested in vitro before implantation even in animals. It is desirable to try to obtain in the laboratory the operational environment that the material will encounter after implantation [73].

In the case of in vivo testing, this is done only under controlled physiological and biophysiological conditions. The biological environment is generally regarded as the sum of the conditions that an implanted material will encounter chronically or acutely, if it is the combination of biological and pericellular conditions. The combination of these extrinsic and intrinsic effects of the environment with the global requirements of the patient during the period proposed for implantation is called the life history of the implant, meaning the totality of the requirements that the biomaterial must meet in order to be successful in the application [74].

The thermal, mechanical, chemical, and surface parameters are sufficient to generally describe the biological environment that the implant encounters. The values differ slightly from patient to patient; the differences that exist have little influence on the response of the host and the material. It is a shame that the technology for determining implant functionality and biomaterial-biological environment interactions is poorly developed compared to that available to biological scientists who study organs in situ.

Within a specific application, the selection of materials and the design of the elements that incorporate them are called “appropriate expectations.” This term does not take into account the changes that occur in the patient’s life after implantation, but it does guide the selection of technologies before implantation. Better said, we try to design the most durable biomaterials and the best surfaces to meet the requirements.

When performing the tests necessary to assess the interactions at the biomaterial-tissue interface, the objective and subjective factors that can influence the response of the tissue, but also that of the biomaterial, are taken into account in order to be able to make a correct interpretation of the results, depending on the material factors and specifically, those related to the surface [75].

In general, there are two intermediate processes common to all implantation applications. First, the implant can be contaminated accidentally or as a result of manufacturing or handling processes during storage or insertion. It is usually assumed that the surface of the implant is pure and clean. The truth can be totally different. Organic elements from manufacturing or improper handling may persist. Oxidation or other harmful elements can occur during the preoperative stages, materials can be lifted from the packaging used to store them, and pathogens can be transferred from surgical instruments.

For this reason, experimental studies on biomaterial-tissue interaction should include surface characteristics of actual implant samples, selected from a batch manufactured for a particular study, under conditions prior to surgical insertion [76].

Second, all implants must be sterilized before use. Some of them may be supplied by the manufacturer in sterile double-wrap packages, while others must be sterilized in a laboratory or hospital before use. Skipping the sterilization process can affect both host and material responses. Sterilization of an implant may render it sterile but not risk-free, thus altering the host’s response. Therefore, in examining the response of the material or the host to the implant, it is necessary to pay more attention to the conditions of surface preparation.

The outcome of an implant replacement is heavily influenced by the interaction between the synthetic material and the surrounding tissue, leading to a diverse range of effects. Implants that come into contact with blood typically require a hemocompatible behavior characterized by minimal interaction to ensure compatibility. In contrast, osseointegrated implants necessitate a strong interaction to achieve high adhesion forces. The process of osseointegration can be influenced by multiple factors, including the surface structure, topography, and composition of the implant material. These aspects play a critical role in facilitating a successful integration with the bone tissue, highlighting the significance of carefully designing implant surfaces to optimize the desired level of interaction and promote favorable outcomes [74].

Many significant factors that individually play a significant role in the effectiveness of implantation influence the direct interaction between tissue and biomaterials. The macrostructure and microstructure of the implant, the surgical implantation technique, the initial tissue-implant contact, the loading conditions on the implant, and the implantation support are some of these aspects. Also included are the biocompatibility of the chosen material. A major obstacle to the placement and operation of metal implants is achieving a sustainable anchoring of the implant in the tissue.

One approach to address tissue anchoring is the use of structured surfaces that promote cell growth, such as porous surfaces. Implants with sandblasted or spherical particle coatings facilitate tissue contact and growth within the interstices of the implant. Another method to enhance surface structure involves creating controlled microstructures with a roughness on the order of a few micrometers. Studies have shown that the superficial layer structure of a metal implant should allow for secondary fixation through the penetration of bone trabeculae into the microcavities of the surface. This surface topography resembles resorbed bone surfaces, which have been utilized as anchor points for newly formed bone. Hence, implant surfaces mimicking the bone structure after resorption are expected to achieve better long-term fixation and stability.

The principle of direct tissue-implant contact requires rigid mechanical fixation, as a soft tissue layer can induce micromovements at the interface. Micromovements can lead to undesirable reactions such as the destruction of the implant’s oxide layer, corrosion, and implant rejection. Rough implants with larger surface areas in contact with tissue are also more susceptible to corrosion processes. Additionally, rigidly fixed metal implants with specific geometries can cause shielding and subsequent bone resorption. These issues highlight the importance of surface preparation, including implant geometry and the arrangement and amplitude of surface elevations and depressions [76].

The surface structure of an implant significantly influences both its fixation and the adhesion force to the surrounding tissue. A soft implant surface with a smaller contact area exhibits lower adhesion force compared to a structured surface. Studies investigating the importance of roughness have demonstrated that increasing roughness enhances adhesion force. Moreover, resistance to breakage increases with greater contact area achieved by introducing holes in flattened cylinders. Adhesion force is also influenced by the duration of implantation, as bone requires time to fill the free space between the implant and surface cavities, leading to mechanical relaxation of the implant.

Beyond the beneficial effects on implant fixation, surface structuring provides advantages in terms of stimulating bone formation. Compressive stress on growing bone generates calcium production, promoting bone growth. This phenomenon becomes more pronounced as charge transfer improves through enhanced surface topography [73].

The biological environment within the human body is chemically, mechanically, and electrically active. The interface between biomaterials and tissue serves as a site for numerous biochemical and biodynamic processes and reactions. Oxygen diffuses from the oxidized surface into the base metal, while metal ions can diffuse onto the surface. Interactions between biological molecules and the implant surface can induce transient or permanent changes in their conformation, resulting in functional alterations.

Understanding and manipulating these complex interactions within the biological environment is critical for optimizing the design and performance of biomaterials in medical applications.

6. Future trends in biomaterials applications

The demand for novel solutions in healthcare and medicine is propelling the rapid advancement of the biomaterials industry. Biomaterials are anticipated to display sophisticated functions in the upcoming years beyond their current uses. These materials will be created with characteristics including self-healing, stimulus responsiveness, and controlled medication release, allowing for customized and focused therapeutic results. The creation of bioactive and bioresorbable materials will also alter the industry since they work with the body’s natural mechanisms to encourage tissue regeneration, degrade over time, or be replaced by fresh tissue.

The emergence of technologies like 3D printing and additive manufacturing will revolutionize the production of biomaterials. These techniques enable precise control over material composition, structure, and geometry, allowing for patient-specific implants, tissue scaffolds, and drug delivery systems. Nanotechnology will also play a significant role, offering unique properties through nanostructured materials such as increased surface area, enhanced mechanical strength, and improved biocompatibility [61].

Biomimetic materials, inspired by nature, will gain prominence in future biomaterials applications. By mimicking the structure and function of natural tissues and organs, these materials enhance biocompatibility and improve integration with the host environment. Furthermore, the combination of biomaterials with other therapeutic approaches such as gene therapy, stem cell therapy, and immunotherapy will lead to innovative treatment strategies and tissue regeneration techniques.

Sustainability and environmental impact will also be important considerations in the future of biomaterials. There will be a shift toward developing biodegradable and environmentally sustainable materials to reduce the long-term ecological footprint of medical devices and promote the use of eco-friendly alternatives.

Additionally, the integration of smart features and sensors into biomaterials will enable real-time monitoring and response to physiological changes. This opens up opportunities for early disease detection, personalized diagnostics, and continuous health monitoring, revolutionizing patient care and management.

As we delve into the exciting realm of biomaterials and their ever-expanding applications, it is essential to address a multitude of evolving factors that are shaping the future of this field. From the innovative potential of nanotechnology in drug delivery to the transformative influence of surface engineering, additive manufacturing, and the integration of Industry 4.0/5.0 and Society 5.0, the landscape of biomaterials is undergoing a profound metamorphosis. Moreover, we explore the pivotal role of digitization, personalization, and the ecological considerations that are becoming increasingly indispensable in the development of medical devices and implants:

• Nanotechnology’s role in drug delivery: In the dynamic landscape of biomaterials, nanotechnology has emerged as a game-changer, particularly in the realm of drug delivery systems. Nanoparticles and nanocarriers hold the potential to revolutionize how medicines are administered, enhancing precision and efficacy.

• Surface engineering and additive manufacturing: Innovations in surface engineering and additive manufacturing techniques have brought exciting possibilities to biomaterials. These advancements allow for the fine-tuning of material properties at the surface level and the creation of intricate structures, paving the way for more customized medical devices and implants.

• Integration of Industry 4.0/5.0 and Society 5.0: An integral part of envisioning the future of biomaterials involves their synergy with the concepts of Industry 4.0 and 5.0, as well as Society 5.0. These paradigms usher in a new era of interconnectedness and intelligent manufacturing, where biomaterials play a central role in the development of smart medical devices and treatments.

• Digital transformation and personalization: As we move forward, the digitization and personalization of medical devices, including biomaterial-based implants, are becoming indispensable. Tailoring medical solutions to individual patients’ needs not only improves treatment outcomes but also minimizes risks and enhances patient satisfaction.

• Environmental considerations: While the focus on patient safety remains paramount, the ecological footprint of biomaterial production should not be overlooked. Inadequate material choices can harm the environment on a larger scale, affecting countless lives. Therefore, sustainability and adherence to ecological requirements are increasingly vital aspects of biomaterial development.

Together, these trends herald a new era in biomaterials science, with far-reaching implications for healthcare and environmental sustainability.

In conclusion, the future of biomaterials applications is filled with exciting possibilities. Advanced functionalities, bioactive materials, 3D printing, nanotechnology, biomimetics, combination therapies, sustainable materials, and smart integration are key trends that will shape the field. These advancements hold great promise for revolutionizing healthcare, enabling personalized treatments, improved patient outcomes, and a brighter future in medical innovation.

7. Conclusion

The chapter on trends in biomaterials applications has shed light on the remarkable advancements and challenges within the field. Biomaterials have proven to be indispensable in various medical applications, offering numerous advantages while also presenting certain limitations. Understanding these trends, advantages, and limitations is significant for researchers, scientists, and healthcare professionals to navigate the ever-evolving landscape of biomaterials.

Furthermore, it is imperative to underscore the critical role of considering allergic reactions in biomedical applications. Careful selection of biomaterials for medical devices should not only account for their mechanical properties but also factor in the potential for allergic responses. This involves a comprehensive understanding of the social, health, and regulatory implications associated with specific materials, such as nickel-containing alloys. In fact, in response to health concerns related to allergic reactions, certain regions, notably the European Union, have enacted stringent regulations leading to the removal of particular materials from biomedical applications.

The advantages of biomaterials, such as metals and alloys, composites, ceramics, and polymers, have been highlighted throughout the chapter. These materials offer unique properties that make them suitable for specific applications. Their mechanical strength, corrosion resistance, biocompatibility, and tailorable properties have played a vital role in the success of implantable devices, orthopedic applications, and tissue engineering.

However, it is equally important to recognize the limitations associated with biomaterials. Factors such as density, wear and corrosion, allergenic reactions, manufacturing complexity, and anisotropy must be considered when designing and selecting biomaterials for medical applications. Addressing these limitations requires continuous research, innovation, and collaboration across disciplines.

The future of biomaterials applications holds tremendous promise. Advancements in biomaterials will continue to drive the development of innovative medical devices, regenerative therapies, and personalized medicine. The integration of advanced functionalities, such as self-healing, stimuli-responsiveness, and controlled drug release, will revolutionize treatment approaches and improve patient outcomes.

Technological advancements, including 3D printing, nanotechnology, and smart materials, will reshape the manufacturing processes and capabilities of biomaterials. These technologies enable the production of patient-specific implants, nanostructured materials, and real-time monitoring systems, leading to personalized diagnostics, tailored therapies, and enhanced healthcare delivery.

Sustainability and environmental considerations are increasingly important in biomaterials research. The development of biodegradable and eco-friendly materials will contribute to reducing the ecological impact of medical devices and aligning healthcare practices with environmental stewardship.

We can conclude that biomaterials are materials engineered to interact with biological systems for medical purposes. These uses highlight the important role that biomaterials play in advancing medical research, better patient outcomes, and improving the quality of life for people with a range of medical illnesses. Future research promises even more advancements as it explores novel biomaterials and inventive medical applications.

In conclusion, understanding the trends, advantages, and limitations of biomaterials applications is essential for advancing the field and improving patient care. By leveraging the strengths of biomaterials while addressing their limitations, researchers and healthcare professionals can harness the full potential of these materials to shape the future of medicine, enabling breakthroughs in diagnostics, treatments, and patient well-being. Continued collaboration, research, and innovation will drive the evolution of biomaterials and pave the way for a new era in healthcare.

Conflict of interest

The authors declare no conflict of interest.