Tissue engineering (TE) is an emerging discipline in the healthcare field that spans multiple domains, including materials chemistry, biological sciences, and engineering. Tissue engineering focuses on addressing today’s globally growing and critical issue: how to tackle tissue failure caused by injuries, diseases, aging, or other forms of damage.

The core concept of tissue engineering lies in developing artificial biomaterials or devices to replace damaged tissues or promote tissue regeneration at sites of defects. In this way, it offers people a new and effective approach to restoring and enhancing the function of human tissues.

Nano-inspired tissue engineering

Nanomaterials have become an important component in tissue engineering (TE) applications due to their unique nanostructural features. The native extracellular matrix (ECM) possesses a complex structure composed of protein fibers and fibrils interwoven within a network of hydrated glycosaminoglycan chains.

This natural EC scaffold provides crucial biophysical support to native tissues, resisting tensile forces through its fibrous structure and counteracting compressive stresses via its hydrated network architecture, thereby possessing appropriate physical properties.

To mimic the physicochemical properties of the ECM, tissue-engineering scaffolds are designed to replicate this naturally complex system.

However, mimicking naturally occurring complex systems inevitably involves multiple aspects; even simply replicating structural features gives rise to numerous possibilities. This is because the extracellular matrix (ECM) exhibits diversity in its physical structure, and the biological environment itself is replete with a wide variety of biomolecules and tissues.

Despite this complexity, scientists have identified a common feature among ECM components: a nanoscale physical structure that plays a crucial role in tissue formation.

For example, in typical connective tissues, protein fibers such as collagen and elastin exhibit nanofibrous structures with diameters ranging from tens to hundreds of nanometers. Similarly, adhesion proteins—such as fibronectin and laminin—that provide specific binding sites for cell adhesion also possess physical structures at the nanoscale.

The morphological characteristics of these ECMs encourage materials chemists to develop nanofiber-based scaffolds for tissue engineering applications. The primary goal of this approach is to establish favorable biophysical and biochemical interactions at the interface between biomaterials and nanomaterials, thereby initiating the tissue regeneration process.

In general, the larger group of materials in this field consists of nanomaterials constructed from various biopolymers, proteins, and minerals. It is worth noting that morphological features at the nanoscale are not the sole criteria for evaluating scaffold materials; these materials should also possess other properties, such as porosity, biodegradability, and biocompatibility.

However, nanomaterials have the potential to positively influence these properties, making them promising candidates for tissue engineering applications.

There is no doubt that nano-based materials have ushered in a new era for the field of tissue engineering over the past few years.

Sustainable nanomaterials

In contrast, today sustainable development has become a concept that commands widespread attention across nearly all fields. At its core, it involves meeting current needs without compromising the ability of future generations to meet their own needs.

Nanotechnology also actively embraces this concept, providing a platform for achieving sustainable development and enhancing its performance across various fields in multiple ways. It is precisely based on these principles that numerous sustainable nanomaterials with tremendous potential have been discovered—particularly in the healthcare sector.

When defining sustainability, it’s important to bear in mind that sustainability is merely a concept; therefore, the sustainability of nanomaterials can be defined from various perspectives, such as their source, properties, and impacts on biological systems. Among these sustainable nanomaterials, three stand out as particularly promising for applications in tissue engineering.

The first type is polysaccharide-based nanomaterials. Polysaccharides are important biopolymers that can form homopolymers or copolymers composed of different monosaccharide units. These biopolymers can be processed into nanomaterials with unique properties suitable for tissue engineering applications.

In nature, polysaccharides are widely found in various organisms, including plants (such as cellulose and starch), algae (such as alginates), microorganisms (such as glucans), and animals (such as chitosan and hyaluronic acid).

Polysaccharides exhibit diversity in terms of their composition, chemical structure, molecular weight, and ionic properties.

This change in properties determines the functions, physicochemical characteristics, and biological activities of polysaccharides. For tissue engineering applications, polymers with linear and long-chain structures are particularly attractive. By employing various techniques such as electrospinning, self-assembly, phase separation, template synthesis, and stretching, polysaccharides can be transformed into nanofiber forms.

The second type is protein-based nanomaterials. Proteins, together with glycoproteins, glycoamino acids, and proteoglycans, constitute an essential component of the extracellular matrix (ECM). These components are critical for endowing tissues with appropriate biophysical properties.

Generally speaking, protein components are fibrous in nature and can form a network structure that provides shear resistance and strength to the primary tissue. In contrast, proteoglycans provide compressive resistance.

These proteins are produced and secreted by tissues through their own cellular mechanisms of specific types, and this process drives mechanical functions such as cell contraction and migration. The interaction between the ECM structure of different tissues and their specific cells determines the unique functions of each tissue. Therefore, using protein-based nanofiber materials to design tissue-engineering scaffolds is an appropriate strategy.

The third type—mineral-based nanomaterials—are an attractive class of sustainable nanoscale structures that can be applied in tissue engineering. In general, minerals are defined as naturally occurring crystalline substances with specific and well-defined chemical compositions. In the case of solid solutions, they may exhibit a certain range of compositions.

For a single mineral with a fixed composition, it exhibits a set of specific physicochemical properties. At the nanoscale, minerals generally adhere to these properties, albeit within a broader range. In reality, the physicochemical properties of nanomaterials vary with changes in their size and are largely influenced by their morphological characteristics.

Therefore, by controlling their morphological parameters, it is possible to tune the various properties of these nanomaterials, thereby facilitating the design of nanoscaffolds with desired characteristics.

It is worth noting that, unlike nanofiber materials based on biopolymers or biological proteins, mineral nanomaterials do not exhibit structural similarity to the extracellular matrix. This is because most nanomaterials are not derived from biological sources (animals, microorganisms, or plants). Nevertheless, these materials still possess highly unique biological properties that make them well-suited for tissue engineering.

In addition to these three highly acclaimed application areas, other diverse types of organic and inorganic nanostructures have also found applications in tissue engineering. These nanomaterials are primarily synthesized artificially in the laboratory using chemicals, reagents, and specialized synthesis techniques.

Although these nanomaterials are not derived from biological sources, they have demonstrated tremendous potential in tissue engineering applications and have already entered the medical products market.

For example, platinum-based nanomaterials and nanocomposites have been widely used in treatments related to bone and dental tissues. In addition, over the past few years, a variety of nanomaterials—including silver, graphene, oxidized graphene, reduced graphene oxide, carbon nanotubes, and carbon dots—have also received extensive research attention.

According to the definition of sustainability, most of these nanomaterials cannot be classified as sustainable materials. However, the current trend in nanomaterial research is to incorporate a certain degree of sustainability into these nanostructures. From synthesis and processing to the application of nanomaterials, a variety of different approaches have already been adopted.

A typical example is the use of bio-based raw materials and reagents in the synthesis of nanomaterials.

For example, plant extracts rich in polyphenols are used as excellent reducing agents and have found applications in the synthesis of various metal nanoparticles. By utilizing extracts from other natural sources such as tea and coconut, green silver nanoparticles with low toxicity and enhanced biocompatibility have been successfully prepared.

These green silver nanoparticles exhibit strong antibacterial activity. Plant extracts have also been successfully used to synthesize metal nanoparticles such as gold, palladium, gold-silver alloys, iron-nickel alloys, iron oxide, and zinc oxide.

In the field of carbon nanomaterials, graphene-based nanomaterials—such as graphene oxide and reduced graphene oxide—play an important role in tissue engineering applications due to their high aspect ratio, cell adhesion capability, and mechanical strength.

Generally, graphene oxide is obtained from graphene via an oxidation-exfoliation method. The conventional approach involves the use of hazardous chemicals such as strong mineral acids and oxidizing agents, which raises concerns about the toxicity of the reagents used.

However, a more sustainable alternative is the electrochemical exfoliation method, which allows direct extraction of graphene flakes from bulk graphite without the need for harmful chemicals, while also delivering superior material properties. In the process of reducing graphene oxide to reduced graphene oxide, various plant extracts have been used as substitutes for traditional reducing agents, such as NaBH4.

Another emerging class of zero-dimensional carbon nanostructures is carbon dots. These nanomaterials possess favorable properties such as water solubility, non-toxicity, and low cost, making them highly promising for a wide range of biomedical applications.

According to reports, incorporating carbon dots into polymer nanocomposites can promote the adhesion, proliferation, and differentiation of osteoblasts. They can also serve as carriers for growth factors in tissue regeneration. By using various renewable resources as raw materials—particularly carbohydrate-rich sources—carbon dots can be sustainably synthesized.

The synthesis process is also very simple, for example, through methods such as heating, hydrothermal treatment, or ultrasonic processing.