Rapid technological development leads to the new generation of well-known materials like glass. It is everywhere, windows, cups, electronics, decorative household elements, windshields, aircraft, jewelry, and much more.

There are many glass types, but one of them ranks as the future leader in the materials market. It is a bioactive glass, which revolutionized regenerative medicine. In this article, we explain what bioactive glass is and what makes it so unusual.

Figure 1. The scheme of the bone reconstruction prosses using bioactive glass. Image Credit: M. Osial

Revolution in bone regeneration discipline

In 1969 Larry Hench and his team discovered bioactive glasses as an alternative to existing implant materials [1]. Based on their work, it was possible to bond that material with the living bone and stimulate bone regeneration called osteogenesis by releasing biologically-active ions. Hench’s invention becomes a revolutionary material with many applications fields in medicine and dentistry, and cosmetology.

Since discovering the first clinical application, we had to wait about ten years [2], but it was worth waiting. The new chapter in the history of modern materials began.

Let’s take a look close to biomaterials history [3]. First implants were known in ancient ages, but their role was only mechanical support. The first generation of biomaterials was used to fill the tissue defects without direct, biological interaction. That implants were mainly made of stainless steel, various alloys, alumina, glass, or silicon rubber. It was impossible to bond those materials to living tissue.

The second generation was able to interact with tissues and elicit biological responses between them and the implant. They were mainly made of metals, ceramics, or polymers that undergo biodegradation (like polylactide that is recently also used in 3D printing and known as PLA). Thanks to their complex structure, the implants stay stable in the placement. However, those materials do not stimulate tissue regeneration. A few percent of implants fail over time or can cause an inflammatory reaction.

Facing that problem, the third generation of biomaterials was created. They are three-dimensional sponge-like porous structures and bioresorbable, making it possible to stimulate the tissue during the regeneration process. The examples of those materials are bioactive glass scaffolds with a well-developed porous structure. The bioactive glass was the first material enabling it to bond with the living tissue. Since their discovery, the reconstruction and regeneration of damaged or lost tissue made the bone’s recovery medicine step forward.

Glass versus bioactive glass 

What is the main difference between the traditional glass we know from our daily life and bioactive glass? An answer lies in the chemical composition [4]. Standard glass is an inorganic material mainly based on silicon oxide SiO2 (or silica) with additives like sodium and calcium carbonates [5].

In general, we can say that glass is a mixture of sand, soda ash, and limestone. Glass is like a solid and liquid simultaneously. Atoms arranged in the glass are close to each other, forming a solid-state. At the same time, their chaotic location is typical for fluids. That is why glass in the window goes thinner at the top and thicker at the bottom in time.

In comparison to the classical glass, the structure of the bioactive glass is a bit different. The secret is hidden in the additives. Its main components are the SiO2 mentioned above and other oxides like CaO, Na2O, and P2O5, which contains calcium, sodium, and phosphorus naturally existing in our body. Their presence and proper ratio in the glass the material biocompatible.

Additives like MgO, Al2O3, K2O, ZrO2, oxides enhance glass’s mechanical and thermal properties, making it resistant to sudden fractures and excessive reaction with biological fluids [6]. Bioactive glass can support damaged tissue. It can interact with the bone through the exchange of particular interactions between ions. These processes between the body and the specific bioactive glass components stimulate the body to direct the healing process.

How to create it?

The bioactive glass formation seems to be relatively easy and cost-effective. That fantastic material can be prepared with several techniques. However, the most frequently used is based on the melting at high temperatures like classical glass or chemical reactions like polymerization (e.g., sol-gel method). Depending on the synthesis way, the bioactive glass may have different properties like density and porosity.

The melting technique gives thick glass for dentistry, while the chemical sol-gel method enables highly porous bone implantation materials [7]. That can be prepared with different shapes and sizes, even structures. Over the decades’ various types of bioactive glasses have been developed to improve their ability to form a bond with mineralized tissues. Their properties are determined by the technique used for the synthesis.

Bioactivity, what is it about?

The main advantage of that material is its bioactivity. But what it really means? The ideal candidate for implants should have antimicrobial properties, stimulate dentin formation, and preserve pulp vitality [8]. Have you ever wondered how it happens that glass can be bioactive and interact with the bones?

In general, when that material is in contact with biological fluids (like saliva, blood, etc.), several chemical reactions and structural changes or the material occur. It leads to its partial dissolution and formation of a hydroxyapatite mineral layer (from CaO and P2O5 – components of bioactive glass) on the glass surface. The hydroxyapatite is a primary mineral building bones, so its formation onto the glass enables bone tissue to stick together to the synthetic mineral-like to the natural one.

Moreover, due to electrostatic and chemical interactions between these layers, collagen fibers can be attached and incorporated. All these processes allow to integrate of the bioactive glass and stimulate tissue regeneration [9].

Thus, glasses’ bioactive properties strongly depend on their chemical composition, manufacturing process parameters, and thermal treatment [10]. The schematic process of bone regeneration is illustrated in Fig. 1. Thus in Fig. 2, the schematic image of bioglass incorporation in bone tissue is shown.

Figure 2. Schematic image of bioglass incorporation in bone tissue. Image Credit: M. Osial

Where to apply it?

Now, we know what bioactive glass is, its composition, synthesis way, so let’s talk about application. We have several possibilities; see Figure 3. The first one is the formation of “fake tissue” for coatings of non-biocompatible implants. For example, classical metal-based implants are exposed to the constant action of body fluids, which means that they will corrode after a while, affecting the living tissues. Covering such an implant with bioactive glass strengthens it and thus slows down corrosion processes and prevents local tissue inflammation.

Moreover, bioactive glass can form bonds between tissues and implants, particularly the dental implants providing additional reinforcement. The second one is the direct application in the bones. When bioactive glass gets in contact with biological fluids, it releases calcium ions what stimulates bone growth. The release of calcium ions is caused by forming a bond between the bioactive glass and bone tissue. Moreover, these ions act on the bacterial colonies and give bioactive glass antibacterial properties.

Another one deals with drugs. Some drugs, due to their properties and absorption method, must be covered with special coatings. Those coatings are determining the drug release rate. The facile synthesis of porous layers of bioactive glass onto various surfaces can be used as a drug coating. The pores present in such a coating allow the drug to release the substance step by step. Other applications are much more associated with everyday life.

Figure 3. Application fields of the bioactive glass. Image Credit: M. Osial

Did you know that?

  • Bioactive glass can be found in cosmetics like nail polish to interact with nail tissue and make it stronger.
  • Bioactive glass can be used in dentistry to regenerate the enamel. You can find it in toothpaste or mouthwash liquid.
  • Bioactive glass can be found in esthetic medicine like hyaluronan in cosmetic dermal fillers to improve the anti-wrinkle effect. You may find it also in cosmetics.

The Future and Challenges

We are witnesses of the revolution in regenerative medicine. It started three decades ago, and today it is in clinical use. Bioactive glass is hope for many people suffering from different bone diseases and supporting various fields. Small steps in its development move forward to many disciplines, but this is not the end. There is still much more to do. The scientists have formulated grand challenges, which stand in front of the bioactive glass [11].

The first one is connected with the creation of Reliable Coatings. The second one includes the redevelopment of the Strong Scaffolds and Self-Healing Implants. Other ones are related to the repair process of damaged bones and the control ingredients in medical devices, which will be used to release the biomolecules and therapeutic ions. Another one is to slow down the aging of living tissues.

The most significant advantage, which is the high superficial speed reaction, which brings rapid connections to the tissues, speaks for bioactive glass’s extensive use. On the other hand, low break resistance is a considerable disadvantage. Thus, one thing is sure the Glass Age, in fact, the Bioactive glass Age, is coming.

This article is a joint work of Magdalena Warczak (Institute of Physical Chemistry, Polish Academy of Sciences), Agnieszka Pregowska (Institute of Fundamental Technology Research), Ewa Klejman (Faculty of Chemistry, University of Warsaw), Magdalena Osial (Faculty of Chemistry, University of Warsaw) as a part of the Science Embassy project. Images Credit: M.Osial

References

[1] Hench L. L., The story of Bioglass TM. J Mater Sci: Mater Med 2006;17:967–78.

[2] Hench L. L., Jones J. R. Bioactive Glasses: Frontiers and Challenges. Front. Bioeng. Biotechnol., 2015.

[3] Larry L. L. L. Thompson I., Twenty-first-century challenges for biomaterials”, J R Soc Interface. 2010; 7: S379–S391

[4] Hmood F., Goerke O., Schmidt F., Chemical Composition Refining of Bioactive Glass for Better Processing Features, Part I. Biomedical Glasses 2018, 4 (1), 82–94.

[5] Zachariasen W. H., The atomic arrangements in glass, Journal of the American Chemical Society 1932, 54, 3841–3851.

[4] El Ghannam A., Ducheyene P., Bioactive ceramics. Comprehensive Biomaterials 2011, 1, 157-179.

[6] Barrioni B. R., de Oliveira A. A. R., Pereira M. The Evolution, Control, and Effects of the Compositions of Bioactive Glasses on Their Properties and Applications. In: Marchi J. (eds) Biocompatible Glasses. Advanced Structured Materials, 2016, 53.

[7] Islam M., Shahruzzaman M., Biswas S., Sakib N., Rashida T. U., Chitosan based bioactive materials in tissue engineering applications-A review. Bioact Mater. 2020, 5 (1), 164–183.

[8] Hench L. L., An Introduction to Bioceramics, 2nd ed.; Imperial College Press: London, UK, 2013.

[9] Dziadek M., Pawlik J., Cholewa-Kowalska K., Bioactive glasses for tissue engineering, Acta Bio-Optica et Informatica Medica Biomedical Engineering, 2014, 20 (3), 157-165.

[10] Baino F., Hamzehlou S., Kargozar S.,  Bioactive Glasses: Where Are We and Where Are We Going? J. Funct. Biomater. 2018, 9 (1), 25.




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