Bioactive vs. Biocompatible: What’s the Difference?

 

Bioactive vs. Biocompatible: What’s the Difference?

Posted Krista Grayson on Dec 1, 2021

The study of biomaterials — substances that are engineered to interact with biological systems for medical purposes — is a relatively new field, but one that has already produced a number of valuable discoveries and treatments.

Over the last few decades, the field has grown rapidly; and, with it, the list of new terms used to describe biomedical devices and materials. In this article, we take a look at two of the most common adjectives in the field, bioactive and biocompatible, and how they are used to describe a range of highly specialized materials.

Essentially, the term biocompatible is used to describe any material which is well-tolerated by the biological system it comes into contact with. At a minimum, most biocompatible materials are chemically inert. In practice, biocompatibility for a given application may depend on any number of other characteristics such as mechanical strength, elastic modulus, or adhesion with the surrounding cellular matrix. It is important to note that biocompatibility is application-specific: a material that is deemed biocompatible in one specific use case may not be biocompatible in another.

Bioactive materials go a step further – these are materials that produce some kind of local physiological response, typically through physical or chemical action. A common example of a bioactive material is bioactive glass: typically silicate-based glass-ceramic materials that are often degradable within the body. Used for bone repair, ion exchange at the surface of bioactive glass leads to the formation of bone-like hydroxyapatite, around which natural bone will readily grow.1 In this way, bioactive glass can actively stimulate the regeneration of bone within a patient.

The term “bioactive” is the opposite of “bioinert”, a word that refers to materials that don’t produce a physiological reaction.

Definitions and Distinctions

If we had to pick “official” definitions of “biocompatible” and “bioactive”, it would probably be those offered by The International Union of Pure and Applied Chemistry (IUPAC), a world authority on standardized scientific nomenclature.2

Bioactive: “Qualifier for a substance which provokes any response from a living system”. IUPAC also notes that the term is often used positively, i.e., to reflect a beneficial change.

Biocompatibility: “The ability to be in contact with a living system without producing an adverse effect.”

These definitions seem simple enough, but there are some subtleties that often cause confusion. These can be cleared up by thinking about how we apply the terms to a very familiar medical device: a contact lens.

Biocompatibility without Bioactivity

Modern contact lenses are made from soft, inert synthetic polymers known as silicone hydrogels. Silicone hydrogel contact lenses are wettable, permeable to oxygen, and cause minimal irritation to the tissues of the eye. We can confidently say, then, that modern contact lenses are highly biocompatible when used properly.

But is a contact lens bioactive? Although a contact lens modifies the light as it enters the eye (resulting in improved vision), the contact lens does not produce a local physiological response with the eye tissue. Thus, we can’t refer to an ordinary contact lens as bioactive.

Note also that “biocompatible” is typically used only in reference to materials, while the term “bioactive” is used to refer to materials or drugs. So, a drug that is tolerated well and without negative side effects would not typically be described as “biocompatible” even though it meets the IUPAC definition.

Mechanisms of Bioactivity

The mechanisms by which bioactivity can occur are numerous and often complex.3 Attempts to engineer bioactive materials often involve emulating intra-cellular signaling, using coatings of proteins or peptides to modulate cell interactions.

There are also many bioactive materials – largely within the category of bioactive glasses and ceramics – which produce a local physiological response through the exchange of simple ions such as silver, fluoride, and calcium.4 These “therapeutic ions” can activate, inhibit or enhance a huge array of cellular pathways, resulting in effects such as antibacterial activity, and stimulation of bone and blood vessel formation.

As research continues and scientists learn more about how different materials can influence cellular processes, we can expect more biocompatible and bioactive materials to find their way into mainstream medical treatment.

Mo-Sci has extensive experience in the manufacture of bioactive glasses. We produce standard compositions, such as 45S5, S53P4, and 13-93, and can also research, develop, and manufacture glass that is customized to fit your application. Contact us to see how we can help with your next product.

References and Further Reading

1. Ferraris, S. et al. Bioactive materials: In vitro investigation of different mechanisms of hydroxyapatite precipitation. Acta Biomaterialia 102, 468–480 (2020).
2. Vert, M. et al. Terminology for biorelated polymers and applications (IUPAC Recommendations 2012). Pure and Applied Chemistry 84, 377–410 (2012).
3. Meyers, S. R. & Grinstaff, M. W. Biocompatible and Bioactive Surface Modifications for Prolonged In Vivo Efficacy. Chem. Rev. 112, 1615–1632 (2012).
4. Baino, F., Hamzehlou, S. & Kargozar, S. Bioactive Glasses: Where Are We and Where Are We Going? JFB 9, 25 (2018).

Glass 101: Using Glass Modifiers to Change Glass Characteristics

 

Glass 101: Using Glass Modifiers to Change Glass Characteristics

Posted Krista Grayson on Sep 16, 2019

Glass modifiers such as lithium oxide, calcium oxide, and zinc oxide can be used to fine-tune the properties of silicate and borate glass to suit a number of niche engineering applications. In this article we take a look at the ways in which common glass modifiers are used to create high-specification glasses for various applications.

Ordinary glass is a unique material. It’s heat-resistant, exhibiting low thermal expansion and excellent thermal shock resistance; chemically durable; exhibits high electrical resistivity; and of course, is highly optically transparent. These properties have made glass an indispensable material in architecture, labware, electronics, and engineering.

Glass can be further transformed into a true wonder-material through the use of glass modifiers. Just like other materials such as steel, the properties of glass can be precisely tuned and augmented through the careful addition of chemical modifiers to suit a huge array of demanding applications.

Glass structure and composition

The constituents of glass can be broadly divided into three categories: network formers, modifiers, and intermediates.1 Network formers form a highly cross-linked network of chemical bonds and constitute the bulk of the glass. Silicon oxide is the most common network-forming constituent of glass, but glasses based on other oxides such as boron and germanium are also commonly produced.

Modifiers are chemicals that can be added to glass in small quantities to further alter the properties of a glass. These include lithium, sodium, potassium, and calcium; which exist as charged single atoms (ions) amongst the cross-linked network formers, reducing the relative number of strong bonds in the glass and lowering the melting point and viscosity. 

Intermediates; which include titanium, aluminum, and zinc; are chemicals that can behave as network-formers or modifiers depending on the glass composition.2 Glasses are naturally highly disordered, and require a carefully tuned balance of network formers, intermediates, and modifiers to prevent the formation of ordered crystallites within the material.

Effects of glass modifiers

As glass generally acts like a solution, the properties of modified glass can be approximately described by additivity relationships: that is, each ingredient contributes to the bulk properties of the glass by an amount roughly proportional to its concentration.3

Glass modifiers interrupt the normal bonding between glass-forming elements and oxygen by loosely bonding with the oxygen atoms. This creates “non-bridging oxygens,” and lowers the relative amount of strong bonding within the glass. As a result, glass modifiers generally have significant effects on glass properties. 

These include a reduction in melting point, surface tension, and viscosity due to weaker overall bonding within the material. These are some of the primary reasons for using glass modifiers – they make glass easier to work with at lower temperatures without affecting transparency.4 Glass modifiers affect the coefficient of thermal expansion, chemical durability, and the refractive index.

Glass modifiers for high-specification applications

Despite a number of common properties, the unique chemical properties of different glass modifiers can have varying effects on the properties of the glass produced. 

Chemical Durability

The use of alkali metals such as sodium and potassium as modifiers generally reduce the chemical durability of glass, whereas alkaline earth metals such as calcium can increase the chemical durability of glass.5

Resistivity

In electronics, the high resistivity and permittivity of glass lend it to applications in resistors and capacitors. The addition of tellurium, germanium or titanium oxides to glasses in low concentrations have been shown to drastically increase resistivity, making them popular as glass modifiers for ultra-high resistance applications such as hearing aids and infrared detectors.6

Glass for labware

Glass with strong chemical durability and resistance to thermal shock is highly valued in labware manufacturing. The addition of zinc oxide to silicate glass can reduce thermal expansion effects, making it especially resistant to thermal shock. Borosilicate glasses, which use borate as well as silicate as a network former, are also especially thermally resistant and chemically durable, making them a popular choice of material for reaction vessels, test tubes, and other labware.

Specialty optical properties

Some glasses are prized for unusual optical characteristics: zinc-modified glass is widely used in photochromic lenses, while silver, gold, and copper can produce photosensitive glass which changes color in response to incident light.4,7

Bioactive glass

Of particular interest to the biomedical community, bioactive glass is a form of modified glass that closely emulates the properties of the mineral portion of living bone. Bioactive glass is highly biocompatible and forms strong chemical bonds with bone. 

This material consists of around 45% silicate with calcium and sodium acting as the primary modifiers. This results in a comparatively soft glass which can be readily machined into implants for use in the repair of bone injuries.8

Mo-Sci leading precision glass technology

Mo-Sci is a world-leader in precision glass technology and produces a range of high-specification glasses for application in healthcare, electronics, and engineering. With expertise including bioactive glass, high refractive index glass, and fluorescent glass; Mo-Sci is able to produce custom solutions for virtually any glass application. Contact us today with your specifications!

References

1. Karmakar, B., Rademann, K. & Stepanov, A. L. Glass nanocomposites: synthesis, properties, and applications.
2. Kienzler, B. Radionuclide source term for HLW glass, spent nuclear fuel, and compacted hulls and end pieces (CSD-C waste). (KIT Scientific Publishing, 2012).
3. Industrial glass | Britannica.com. Available at: https://www.britannica.com/topic/glass-properties-composition-and-industrial-production-234890#ref608298. (Accessed: 17th May 2019)
4. Phillips, G. C. A Concise Introduction to Ceramics. (Springer Netherlands, 1991). doi:10.1007/978-94-011-6973-8
5. Hu, J. MIT 3.071 Amorphous Materials 2: Classes of Amorphous Materials. https://ocw.mit.edu/courses/materials-science-and-engineering/3-071-amorphous-materials-fall-2015/lecture-notes/MIT3_071F15_Lecture2.pdf
6. Weißmann, R. & Chong, W. Glasses for High-Resistivity Thick-Film Resistors. Adv. Eng. Mater. 2, 359–362 (2000).
7. Photosensitive glass. (1948). https://patents.google.com/patent/US2515275
8. Rahaman, M. N. et al. Bioactive glass in tissue engineering. Acta Biomater. 7, 2355–2373 (2011).

Reducing Implant-Related Infection with Bioactive Glass

 

Reducing Implant-Related Infection with Bioactive Glass

Posted Krista Grayson on Feb 13, 2019

Disease, trauma or serious infection may result in extensive bone damage or bone loss which exceeds the body’s capacity to repair itself. In such cases, implants are needed to promote satisfactory healing. These may take the form of screws, plates, or rods to immobilize broken bones in the correct alignment, reinforce weak bones or correct skeletal deformities. Similarly, diseased joints can be replaced with prosthetic joints to restore normal, pain-free movement. 

Despite ongoing medical advances and improvements in materials and procedures, there remains a substantial risk of implanted devices becoming infected. In addition to microbes being introduced into the body during surgery, there is the risk of bacteria transported in the blood from other parts of the body colonizing the surface of an implant. It has been estimated that as many as 2.5% of primary hip and knee replacements and to 10% of joint revision surgeries are complicated by infection.1 Infected implanted devices represent a significant clinical challenge. Typically, despite lengthy antibiotic treatments, it is often necessary for the infected implant to be surgically removed. This not only increases patient morbidity and dissatisfaction, but is also associated with substantial cost.2 

Antibiotics continue to be the mainstay strategy for both the prevention and treatment of implant infections. However, the power of antibiotics in the fight against infection is diminishing as many strains of potent bacteria are developing resistance to even the strongest antibiotics. Consequently, the risk of implanted devices becoming infected is on the rise and researchers are investigating novel ways to reduce such infections.

One strategy is based on the discovery that the majority of bacteria live in surface-bound microbial communities, rather than as free-swimming entities. On binding to the surface, bacteria secrete adhesion proteins that provide an irreversible attachment.3 Such bacterial biofilms account for over 80% of clinical microbial infections.2 It was therefore proposed that making the surface of implants unsuitable for bacterial colonization would dramatically lower infection rates. This can be achieved by coating the implant with bioactive glass.

The Antimicrobial Properties of Bioactive Glass

Bioactive glass is a type of glass made from high-purity chemicals, such as silica, calcium, and boron, which induce specific biological activity.4 Bioactive glass, by virtue of its high strength, low weight and biocompatibility, has been widely used in a range of biomedical applications, including tissue engineering, bone grafting, dental reconstruction and wound healing.5 

Such clinical experience has shown that borate bioactive glass possesses antimicrobial properties against a wide range of bacteria, including MRSA and E-coli.6,7 The antimicrobial efficacy is achieved though an increase in pH of the surrounding body fluids (which is stressful for bacteria) and because any bacteria that do approach are unable to adhere to bioactive glass and so cannot create microfilms on its surface.8,9 In vitro studies have confirmed that bioactive glass has strong anti-staphylococcal and anti-streptococcal activity.10,11

Since the antimicrobial action of bioactive glass arises from it creating an environment that is hostile to bacteria rather than requiring direct contact with the invading microbe in order to kill it, it is effective across a wide range of bacteria. Furthermore, the bacteria cannot adapt to such effects, and so no bacteria have been found to develop resistance to the antimicrobial effects of bioactive glass.9 

Coating Implants with Bioactive Glass

Initial technical challenges have been overcome and a range of titanium implants have been successfully coated with bioactive glass.12 Clinical use of implants coated with bioactive glass has given promising results in both orthopedic and dental applications. There was no evidence of the coated implants causing any adverse effects or inflammatory response in the surrounding tissue. Furthermore, the implants coated with bioactive glass were found to accelerate cell attachment and mineralization of the extracellular matrix, promoting more rapid bone growth. In addition, the proportion of bone-to-implant contact was significantly greater for implants coated with bioactive glass compared with traditional implants.13-15

Enhancing the Antimicrobial Efficacy of Bioactive Glass

Bioactive glass has good antimicrobial action, being effective against a broad spectrum of aerobic and anaerobic bacteria.9 However, the antimicrobial effects can be further enhanced to increase the range of antimicrobial activity, by the addition of ions, such as boron, copper, silver, yttrium, and iodine, or organic nanoparticles.16,17 The chosen antimicrobial agent is incorporated into the bioactive glass during its production and released once the bioactive glass is in an aqueous solution, creating an environment inhospitable for microbial life. The bioactive glass can thus be used as a delivery system for antimicrobials.18

The advantage of ions and nanoparticles over antibiotics is that their efficacy depends solely on contact with the bacterial cell wall; they do not need to enter the cell. Consequently, their lethal effect is delivered irrespective of the specific genetics of the target bacteria and is unaffected by the resistance mechanisms used by bacteria to evade antibiotics.

Conclusion

Infection of medical implants is an increasingly serious clinical and socioeconomic burden. Furthermore, the situation is likely to worsen with the increasing prevalence of bacteria with multi-drug resistance. 

Bioactive glass has inherent antimicrobial activity and does not elicit a toxic response to surrounding tissues. Consequently, coating implants with bioactive glass represents an attractive option for reducing the risk of infection. The antimicrobial properties of bioactive glass can be further enhanced by loading it with antimicrobial agents, such as ions or antibacterial nanoparticles. Such a strategy would reduce the need for prophylactic antibiotic use, whereby protecting against the development of further strains of antibiotic-resistant bacteria. 

Since bacteria cannot adapt to the hostile environment created by bioactive glass or its biofilm-resistant surface, they are unlikely to develop resistance to the antimicrobial action of bioactive glass. 

In addition, the coating of implants with bioactive glass has been shown to speed up the fusion of the implant with bone, accelerating a patient’s recovery.

The use of bioactive glass, either alone or doped with antimicrobial agents, as a coating for orthopedic and dental implants is thus likely to improve the success rate and enhance patient outcomes across a range of reparative and restorative surgeries by promoting rapid healing and minimizing the occurrence of infection. 

Mo-Sci produces high quality bioactive glass powders, the precise composition of which can be tailored to meet specific requirements. They produce bioactive glass suitable for coating orthopedic and dental implants.

References & Further Reading

1. Lentino JR. Prosthetic joint infections: Bane of orthopedists, challenge for infectious disease specialists. Clin Infect Dis. 2003;36:1157–61. doi: 10.1086/374554.
2. Hall-Stoodley L, et al. Bacterial biofilms: from the natural environment to infectious diseases. Nature Reviews Microbiology2004;2(2): 95–108.
3. Davey ME and O’Toole GA. Microbial biofilms: from ecology to molecular genetics. Microbiology and Molecular Biology Reviews2000;64(4):847–867.
4. Brauer DS. Bioactive Glasses—Structure and Properties. Angew Chem Int Ed 2015;54: 4160–4181.
5. Rahaman MN, et al. Bioactive glass in tissue engineering. Acta Biomaterialia 2011;7:2355?2373.
6. Ottomeyer M, et al. Broad-Spectrum Antibacterial Characteristics of Four Novel Borate-Based Bioactive Glasses. Advances in Microbiology 2016;6:776?787.
7. Khvostenko D, et al. Bioactive glass fillers reduce bacterial penetration into marginal gaps for composite restorations. Dental materials 2016;32(1):73–81. Available at http://www.demajournal.com/article/S0109-5641(15)00437-6/pdf
8. Zhang D, et al. Factors Controlling Antibacterial Properties of Bioactive Glasses. Key Engineering Materials 2007;330-332:173?176.
9. Drago L, et al. Recent Evidence on Bioactive Glass Antimicrobial and Antibiofilm Activity: A Mini-Review Materials 2018;11:326?337.
10. Misra SK, et al. Poly(3-hydroxybutyrate) multifunctional composite scaffolds for tissue engineering applications. Biomaterials 2010;31:2806–2815.
11. Rivadeneira J, et al. In vitro antistaphylococcal effects of a novel 45S5 bioglass/agar-gelatin biocomposite films. J Appl Microbiol 2013;115,604–612.
12. Lopez-Esteban S, et al. Bioactive glass coatings for orthopedic metallic implants. Journal of the European Ceramic Society 2003;23:2921–2930.
13. Mehdikhani-Nahrkhalaji M, et al. Biodegradable nanocomposite coatings accelerate bone healing: In vivo evaluation. Dent Res J (Isfahan). 2015;12(1):89?99.
14. Chen Q, et al.Cellulose Nanocrystals–Bioactive Glass Hybrid Coating as Bone Substitutes by Electrophoretic Co-deposition: In Situ Control of Mineralization of Bioactive Glass and Enhancement of Osteoblastic Performance. ACS Appl Mater Interfaces. 2015 Nov 11;7(44):24715?25.
15. van Oirschot BA, et al. Comparison of different surface modifications for titanium implants installed into the goat iliac crest. Clin Oral Implants Res. 2016;27(2):e57?67.
16. Kaur G, et al D. Review and the state of the art: Sol–gel and melt quenched bioactive glasses for tissue engineering. J Biomed Mater Res B Appl Biomater 2016;104, 1248–1275.
17. Karwowska E. Antibacterial potential of nanocomposite-based materials – a short review. Nanotechnology Reviews 2016;6(2):243?254.
18. Rivadeneira J and Gorustovich J. Bioactive glasses as delivery systems for antimicrobial agents. Journal of Applied Microbiology 2016;122, 1424–1437.
19. Mo Sci Corporation website. http://www.mo-sci.com/en/products

Inhibiting Bacterial Growth with Bioactive Glass

 

Inhibiting Bacterial Growth with Bioactive Glass

Posted Krista Grayson on Jan 14, 2019

Despite numerous advances in technologies, bacteria remain a cause for concern in both clinical and industrial settings. They pose an especially challenging problem in medicine where only bactericidal strategies which have a minimal detriment to human health are feasible, and bacterial infection continues to be a leading cause of morbidity and mortality.

Surgical procedures in particular are associated with an increased risk of infection, and infection is the most frequently encountered post-surgical complication. The primary means of prevention and treatment of bacterial infections is the administration of antibiotics. However, the power of antibiotics in the fight against infection is diminishing as strains of potent bacteria are developing multi-drug-resistance.

In contrast to historical beliefs, it is now apparent that the majority of bacteria live in surface-bound microbial communities, rather than as free-swimming entities. On binding to the surface, bacteria secrete adhesion proteins that provide an irreversible attachment. The bacteria proceed to proliferate and create a colony that ultimately results in the formation of a mature biofilm protected by a peptidoglycan envelope.1 Such biofilms account for over 80% of clinical microbial infections, and so are associated with considerable morbidity and expense.2

In addition to the possibility of biofilms containing antibiotic-resistant strains, the bacteria are protected from antibacterial agents and the body’s immune system by the peptidoglycan envelope. Biofilm-associated bacteria are 100 to 1,000 times less susceptible to antibiotics than free-swimming bacteria, and so patients with biofilm infections are rarely cured by treatment with antibiotic agents, which are used nonetheless due to the lack of alternatives. Furthermore, there is the scope for bacteria to leave the biofilm and colonize other areas throughout the body.

Consequently, there has been much research in to the development of new broad-spectrum antibiotics and also novel antimicrobial strategies.

Novel antimicrobial materials

Nanotechnology has opened up the potential for the development of new types of materials with antimicrobial properties. It allows the physicochemical properties of a material to be changed in order to achieve antimicrobial effects.3

Antimicrobial nanomaterials include a wide range of metal, metal oxide, and organic nanoparticles and so have numerous modes of action. Although a range of chemical interactions are involved, the end result is membrane damage that leads to loss of integrity and impaired metabolism and ultimately cell death.

The advantage of nanoparticles over antibiotics is that their efficacy depends solely on contact with the bacterial cell wall; they do not need to enter the cell. Consequently, their lethal effect is exerted irrespective of the specific genetics of the target bacteria and is unaffected by the resistance mechanisms used by bacteria to evade antibiotics. Furthermore, the large surface area to size ratio of nanoparticles means that high activity can be achieved with a small dose, whereby minimizing the risk of toxicity. It is therefore hoped that nanoparticles may provide an effective alternative to antibiotics for the treatment of both free-swimming and surface bound bacteria.

Nanoparticles could be used in antimicrobial treatments and in the manufacture of nanocomposite products suitable for use in medical materials and devices.

Bioactive glass

Bioactive glass is a type of glass made from high-purity chemicals, such as silicon oxide, calcium oxide, and phosphorus oxide, that induces specific biological activity.4 Furthermore, by modifying the composition and structure of the glass, its physical properties can be tailored to meet a specific need.4

Bioactive glass elicits a negatively benign immune response and has been widely used in a range of biomedical applications, including tissue engineering, bone grafting, dental reconstruction and wound healing.5 It is able to bond to either hard or soft tissue and has been shown to facilitate strong new bone growth, promote soft tissue regeneration and enhance vascularization to ensure a healthy blood flow to the newly regenerated tissue.6–8 It has also been mixed with dental filling materials to promote the remineralization of dental caries.9

In addition, borate bioactive glass has been shown to have antimicrobial properties against a wide range of bacteria, including MRSA and E-coli.10 It has been shown that bacteria are unable to adhere to bioactive glass and so microfilms cannot develop on its surface.11 This is supported by clinical observations; no infections have been reported on bioactive glass implants.11 In addition, the inclusion of bioactive glass into dental filling material reduced bacterial penetration by 40%, whereby reducing the rate of decay and increasing the lifetime of the restoration.12

The antimicrobial action of bioactive glass can be further increased, giving the glass a broader spectrum of antimicrobial activity, by the addition of ions such as silver, yttrium, selenium, and iodine.13

The use of bioactive glass fibers to promote wound healing and soft tissue repair and the inclusion of bioactive glass in bone grafting and dental restoration composite materials to promote bone growth thus gives dual benefit — more rapid healing and reduced risk of infection.

Mo-Sci produces implant grade bioactive glass powders of varying sizes and with specific compositions suitable for mixing with composite materials.14

References

1. Davey ME and O’Toole GA. Microbial biofilms: from ecology to molecular genetics. Microbiology and Molecular Biology Reviews 2000;64(4):847–867.
2. Hall-Stoodley L, et al. Bacterial biofilms: from the natural environment to infectious diseases. Nature Reviews Microbiology 2004;2(2): 95–108.
3. Karwowska E. Antibacterial potential of nanocomposite-based materials – a short review. Nanotechnology Reviews 2016;6(2):243?254.
4. Brauer DS. Bioactive Glasses—Structure and Properties. Angew Chem Int Ed 2015;54: 4160–4181.
5. Rahaman MN, et al. Bioactive glass in tissue engineering. Acta Biomaterialia 2011;7:2355?2373.
6. Gerhardt L-C and Boccaccini AR. Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering. Materials 2010;3:3867?3910
7. Pugely AJ, et al. Influence of 45S5 Bioactive Glass in A Standard Calcium Phosphate Collagen Bone Graft Substitute on the Posterolateral Fusion of Rabbit Spine. Iowa Orthop J. 2017; 37: 193–198.
8. Gorustovich A, et al. Effect of bioactive glasses on angiogenesis: In-vitro and in-vivo evidence: A review. Tissue Eng. Part B Rev. 2010;16:199?207.
9. Chatzistavrou X, et al. Fabrication and characterization of bioactive and antibacterial composites for dental applications. Acta Biomater. 2014;10:3723–3732. Available at https://www.ncbi.nlm.nih.gov/pubmed/24050766
10. Ottomeyer M, et al. Broad-Spectrum Antibacterial Characteristics of Four Novel Borate-Based Bioactive Glasses. Advances in Microbiology 2016;6:776?787.
11. Zhang D, et al. Factors Controlling Antibacterial Properties of Bioactive Glasses. Key Engineering Materials 2007;330-332:173?176.
12. Khvostenko D, et al. Bioactive glass fillers reduce bacterial penetration into marginal gaps for composite restorations. Dental materials 2016;32(1):73–81. Available at http://www.demajournal.com/article/S0109-5641(15)00437-6/pdf
13. Xu Y, et al. Study on the Preparation and Properties of Silver-Doped Borosilicate Antibacterial Glass. Journal of Non-Crystalline Solids 2008;354:1342?1346.
14. Mo Sci Corporation website. http://www.mo-sci.com/en/products.

Bioactive Glass as a Bone Graft Substitute

 

Bioactive Glass as a Bone Graft Substitute

Posted Krista Grayson on May 16, 2018

Between 1992 and 2007, bone grafting was used in the treatment of almost two million patients in the United States.1 Bone grafts are used to facilitate the healing of complex bone trauma. This may be a multiple fracture or non-union of a long bone fracture, loss of bone due to disease, or surgical implantation of devices, like joint replacements, plates, or screws.

Bone grafting typically uses bone from another part of the patient’s body, such as ribs, hips, or pelvis, (an autograft) or bone harvested from a deceased donor or a cadaver that has been cleaned and stored in a tissue bank (an allograft). 

Despite grafting markedly improving bone regeneration and clinical outcomes after severe bone injury or loss, there is still room for improvement. Researchers continue to investigate ways to enhance bone grafting techniques and provide faster and denser bone regeneration with lower morbidity.

One such development has been the use of bone graft substitutes, such as demineralized bone matrix, calcium phosphates, collagen- /hydroxyapatite-based substitutes, and bone morphogenetic proteins. Although autologous bone grafting was considered to be the preferred bone grafting modality,2 there is a trend towards favoring artificial bone grafts over autografts since they are readily available and obviate the need for additional surgery. However, bone graft substitutes can have limitations regarding strength under torsion.

Bioactive glass, by virtue of its biocompatibility, strength and range of achievable properties, has been widely used to facilitate bone repair and provide support in tissue engineering.3

The Different Types of Bone Grafting

Bone grafting is a surgical procedure that is beneficial for repairing bones that have been severely damaged by trauma and for replacing bone that is missing as a result of either trauma or disease. It can also be used to strengthen bone at the site of an implant, be that a joint replacement, screw or dental implant. The bone graft provides a framework to support and encourage the growth of new, living bone.

Autografts have long been considered the preferred means of bone grafting since they do not carry the risk of rejection. However, these necessitate additional surgery, which increases patient morbidity and the risk of infection. Furthermore, there may be issues with availability finding a suitable site to harvest bone of the needed shape and size.

Allografts obviate the need for additional incisions but carry the risk of immune response preventing the graft from being accepted. There is also still the potential for availability issues since the donated bone needs to be tissue matched with the patient. 

A third option is not to rely on bone at all for the graft, but instead to use a man-made substitute. A range of different materials, including calcium phosphates, collagen, hydroxyapatite, have been investigated for use in bone grafting and are readily available. When using bone substitutes the nature of the materials must be carefully considered in terms of biocompatibility, resorption rate and strength.

Bone Graft Substitutes

The formation of new bone requires three key processes: osteogenesis (synthesis of new bone), osteoinduction (recruitment of stem cells and their differentiation into bone cells), and osteoconduction (the development of adequate blood supply to the new bone and correct structuring of the new bone cells). Bone graft substitutes are designed to facilitate and enhance these processes to promote rapid development of strong new bone.

Bone graft substitutes are frequently used to fill bone defects after orthopedic trauma. Ideally a synthetic bone graft substitute would have efficacy at least comparable to autograft, no immunogenicity, osteoinductive and osteoconductive properties, predictable resorption/degradation time, and no safety concerns. 

Numerous studies have reported benefits of using synthetic bone substitutes for fracture treatment and spinal surgery.4,5,6,7 These include reduced pain, bleeding and healing time, and improved functional outcomes compared with autografts. However, there have been safety concerns and problems with unpredictable resorption rates with some of the bone substitute materials.8

Furthermore, the different bone substitute products have varying characteristics. They all only provide minimal structural integrity and none targets all three of the key bone formation processes.9 Although some bone substitutes closely mimic the structure of natural bone, they lack osteogenic and osteoinductive properties. 

Bioactive glass has been successfully used in a range of tissue engineering procedures.3 With its versatility, achieved through the tailoring of properties through composition adjustments, its intrinsic strength and biocompatibility, bioactive glass was considered a prime candidate for improving synthetic bone substitutes.

Bioactive Glass for Bone Grafting

Introduction of bioactive glass into the body induces specific biological activity that causes soluble ionic species to be released. These lead to the glass becoming coated with a substance similar to hydroxyapatite. The formation of this layer allows bioactive glass to bond firmly with both hard and soft tissues. Furthermore, bioactive glass can be manufactured to release nutrients required for bone regeneration.

It has been shown that damaged bone regained its original strength more quickly when repaired using composite combined with bioactive glass compared with bone repair using composite alone and that the efficacy achieved is comparable to that of autologous bone grafting.10,11

A recent study compared spine fusion in rabbits using a mineralized collagen bone substitute with and without added bioactive glass. The bioactive glass-collagen composite was shown to closely mirror repair by autograft in terms of the amount and quality of the new bone.12 In addition, fusion occurred earlier when the collagen composite was augmented with bioactive glass.13

Conclusion

Bone grafting is an important tool for the repair of damaged or disease bone. The gold standard is autografting, which uses bone harvested from the patient to avoid rejection reactions. However, the increased morbidity caused by the additional surgery needed to acquire bone for grafting has resulted in an on-going quest to find an alternative. Bone substitutes have shown efficacy, but do not promote the formation of new bone. Bioactive glass is biocompatible and enhances strong new bone creation. Studies have now shown that the addition of bioactive glass to bone substitutes can increase their efficacy and bone healing characteristics to rival those achieved with autografting.

Mo-Sci produces medical implant grade bioactive glass in a form suitable for mixing with bone composites and can tailor its composition to meet specific requirements.13

References

1. Kinaci A, et al. Trends in Bone Graft Use in the United States. Orthopedics 2014;37(9):e783 e788.
2. Flierl MA, Outcomes and complication rates of different bone grafting modalities in long bone fracture nonunions: a retrospective cohort study in 182 patients. J Orthop Surg Res. 2013;8:33.
3. Rahaman MN, et al. Bioactive glass in tissue engineering. Acta Biomaterialia 2011;7:2355 2373.
4. Bajammal SS, et al. The use of calcium phosphate bone cement in fracture treatment: a meta-analysis of randomized trials. J Bone Joint Surg [Am] 2008;90-A:1186-1196.
5. Swiontkowski MF, et al. Recombinant human bone morphogenetic protein-2 in open tibial fractures: a subgroup analysis of data combined from two prospective randomized studies. J Bone Joint Surg [Am] 2006;88-A:1258 1265.
6. Lerner T, et al. A level-1 pilot study to evaluate of ultraporous beta-tricalcium phosphate as a graft extender in the posterior correction of adolescent idiopathic scoliosis. Eur Spine J 2009;18:170-9.
7. Dimar JR, et al. Clinical and radiographic analysis of an optimized rhBMP-2 formulation as an autograft replacement in posterolateral lumbar spine arthrodesis. J Bone Joint Surg [Am] 2009;91-A:137 186.
8. Carragee EJ, et al. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 2011;11:471 191.
9. American Academy of Orthopaedic Surgeons. Bone-grafts: Facts Fictions and Applications. Presented at 70th Annual General Meeting. Louisiana 2003. Available at https://www.aaos.org/research/committee/biologic/bi_se_2003-1.pdf
10. Havener MB, et al. Improvements in Healing with a Bioactive Bone Graft Substitute in a Canine Metaphyseal Defect. Poster at 55th Annual Meeting of the Orthopaedic Research Society. February 22–25, 2009
11. Jia W, et al. Bioactive Glass for Large Bone Repair. Adv Health Mater. 2015;4(18):2842 2848.
12. Pugely AJ, et al. Influence of 45S5 Bioactive Glass in A Standard Calcium Phosphate Collagen Bone Graft Substitute on the Posterolateral Fusion of Rabbit Spine. Iowa Orthop J. 2017; 37: 193–198.
13. Mo Sci Corporation website. http://www.mo-sci.com/en/products

Developing Bacteria-Resistant Tooth Fillings Using Bioactive Glass

 

Developing Bacteria-Resistant Tooth Fillings Using Bioactive Glass

Posted Krista Grayson on Jan 30, 2018

Photo by Lesly Juarez on Unsplash

Recently, with concerns over the potential toxicity of amalgam (silver fillings) and customer preference for less conspicuous fillings, there has been an increasing trend towards the use of composite (white fillings) materials for repairing dental decay. More than 122 million composite tooth restorations are made in the United States every year.2

Composite fillings are generally made from synthetic resins that are softer than natural tooth material, and so they are more susceptible to failure than amalgam (lasting 6-10 years versus several decades, respectively). However, all fillings will fail at some point as they crack or shrink away from the tooth. In both cases, the resultant gaps can harbor bacteria and food debris, increasing the risk of further tooth decay. The most common reason for replacement fillings is secondary caries occurring at the margins.

There has consequently been much research into developing a more durable filling material for the repair of dental decay, whilst still maintaining the aesthetic value.

Since bioactive glass is known to be biocompatible and is already used for many biomedical applications, its potential in dentistry has been explored. This article discusses the use of bioactive glass as a dental filling material. 

What is Bioactive Glass?

Glass does not elicit an immune response and so, by virtue of its high strength and low weight, has been widely used in a range of biomedical applications, including bone tissue engineering, bone regeneration and wound healing.4 Bioactive glass is a type of glass that is able to bond to either hard or soft tissue and also demonstrates antimicrobial activity. 

Bioactive glass is made from high purity raw materials, such as silicon oxide, calcium oxide, and phosphorus oxide, melted in platinum crucibles.5 They are available as discs, spheres, fibers and powders of varying sizes and with specific compositions.6 Furthermore, by modifying the composition and structure of the glass, its physical properties can be tailored to meet a specific need.5

Dental Bioactive Glass Composites

Following the success of bioactive glass in orthopaedic applications, bioactive glass was adopted for use in dentistry applications. It has shown substantial benefit in the repair of periodontal defects.4 

The observed antimicrobial activity alongside its demonstrated high strength made bioactive glass a prime candidate for tooth fillings. Fillings made with bioactive glass should slow secondary tooth decay by inhibiting bacterial colonization and increase the durability of composite filling materials. Furthermore, it was hypothesized that the bioactive glass may also provide minerals to strengthen the damaged surface of the tooth.

Evaluations of bioactive glass as a tooth filling have recently shown that such extrapolations to dentistry are indeed correct. Studies have demonstrated that the addition of bioactive glass to dental filling materials enhanced mineral formation in the dentin, promoting remineralization of dental caries7 and improved the mechanical properties of a filling in an aqueous environment.8 The latest research has shown that restorations made with a composite filling materials mixed with bioactive glass filler are significantly less prone to bacterial penetration.9 The proportion of the gap depth colonized with bacteria was 61% when a filler incorporating bioactive glass was used, compared with 100% for the conventional filler. 

Based on these findings the addition of bioactive glass to composite filling material may increase the durability of composite fillings while also reducing the incidence of secondary tooth decay at restoration margins.

Conclusion

Secondary decay at the site of tooth restorations is an ongoing challenge in dentistry. Tooth fillings that utilize bioactive glass composites have been shown to reduce bacterial colonization and strengthen composite fillings. This translates to a reduced rate of decay and increased lifetime of the restoration. The addition of bioactive glass to dental filler materials thus have the potential to offer patients requiring dental restorations a less problematic solution. 

Jamie Kruzic, a professor and expert in advanced structural and biomaterials in the Oregon State University College of Engineering, highlighted the benefits of incorporating bioactive glass into dental filling materials “This type of glass is only beginning to see use in dentistry, and our research shows it may be very promising for tooth fillings. The bacteria in the mouth that help cause cavities don’t seem to like this type of glass and are less likely to colonize on fillings that incorporate it. This could have a significant impact on the future of dentistry”.

References

1. National Institutes of Health. NIDCR Data & Statistics. Dental Caries (Tooth Decay) in Adults (Age 20 to 64). Available at: https://www.nidcr.nih.gov/DataStatistics/FindDataByTopic/DentalCaries/DentalCariesAdults20to64.htm
2. Stauth D. New study: Bioactive glass prolongs the life of tooth fillings Dentistry IQ, 5 January 2106. Available at http://www.dentistryiq.com/articles/2016/01/new-study-bioactive-glass-prolongs-the-life-of-tooth-fillings.html
3. Marks LAM, et al. Dyract versus Tytin class II restorations in primary molars: 36 months evaluation. Caries Research. 1999;33:387–392.
4. Rahaman MN, et al. Bioactive glass in tissue engineering. Acta Biomaterialia 2011;7:2355 2373.
5. Brauer DS. Bioactive Glasses—Structure and Properties. Angew Chem Int Ed 2015;54: 4160–4181.
6. Mo Sci Corporation website. http://www.mo-sci.com/en/products
7. Prabhakar AR, et al Comparative Evaluation of the Remineralizing Effects and Surface Micro hardness of Glass Ionomer Cements Containing Bioactive Glass (S53P4):An in vitro Study. Int J Clin Pediatr Dent. 2010 May-Aug;3(2):69-77. doi: 10.5005/jp-journals-10005-1057. Available at https://www.ncbi.nlm.nih.gov/pubmed/27507915.
8. Chatzistavrou X, et al. Fabrication and characterization of bioactive and antibacterial composites for dental applications. Acta Biomater.
9. 2014;10:3723–3732. Available at https://www.ncbi.nlm.nih.gov/pubmed/24050766
10. Khvostenko D, et al. Bioactive glass fillers reduce bacterial penetration into marginal gaps for composite restorations. Dental materials 2016;32(1):73–81. Available at http://www.demajournal.com/article/S0109-5641(15)00437-6/pdf