Abstract
Objective
Nowadays bioactive glasses are finding increasing applications in medical practice due to their ability to stimulate re-mineralisation. However, they are intrinsically brittle materials and the study of new compositions will open up new scenarios enhancing their mechanical properties and maintaining the high bioactivity for a broader range of applications. This systematic review aims to identify the relationship between the composition of bioactive glasses used in medical applications and their influence on the mechanical and biological properties.
Methods
Various electronic databases (PubMed, Science Direct) were used for collecting articles on this subject. This research includes papers from January 2011 to March 2016. PRISMA guidelines for systematic review and meta-analysis have been used. 109 abstracts were collected and screened, 68 articles were read as relevant articles and a total of 22 papers were finally selected for this study.
Results
Most of the studies obtained enhanced mechanical properties and the conservation of bioactivity behaviours; although a lack of homogeneity in the characterization methods makes it difficult to compare data.
Significance
New compositions of bioactive glasses incorporating specific ions and the addition in polymers will be the most important direction for future researches in developing new materials for medical applications and especially for dentistry.
1
Introduction
In 1969, Hench et al. developed a new material for medical applications; creating a solid base for the following 40 years of research in the bone/tissue regeneration field. 45S5 was the first bioactive glass generated, with a composition showing an excellent biocompatibility. Its composition by weight is: 45% SiO 2 , 24.5% Na 2 O, 24.5% CaO and 6% P 2 O 5 . This material is able to bond with bone and stimulates bone growth due to hydroxy-carbonate apatite (HCA) formation. This type of apatite is chemically and structurally very similar to the mineral phase of hard tissues.
Bonding to bone and tissues has been well documented and investigated by a large series of bioactive glass compositions . The mechanism of bone bonding enables the bioglass (BG) to develop an adherent interface with tissues that resists mechanical forces. In many cases, the interfacial strength of adhesion is equivalent to or greater than the cohesive strength of the implanted material or the tissue bonded to the bioactive implant. Five steps have been described for bone-bounding mechanism in bioactive glass :
- •
Step 1: fast release of Na + and Ca 2+ ions which are exchanged with the H 3 O + ions present in the solution. A rapid increase of solution pH develops.
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Step 2: network silica is attacked by hydroxyl groups causing the formation of Si(OH) 4 in the solution.
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Step 3: Silanols (−Si OH groups) form a silica rich layer on the surface thanks to re-polymerization reactions.
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Step 4: Ca 2+ and PO 4 3− migrate to the newly formed silica surface forming a CaO–P 2 O 5 film on top.
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Step 5: CaO–P 2 O 5 film crystallize and incorporate other ions from the solution (such as OH − and CO 3 − ) will form a HCA layer.
For the treatment of bone defects or dental trauma as well as diseases such as osteoporosis, cancer and infectious diseases, it is essential to develop new active materials that are able to interact with host surroundings, enhancing and directing complete tissue healing, repair and regeneration. Synthetic biocompatible materials are used to replace damaged tissues but the weakness of some chemical, biological and/or physical properties results in implant failure that requires retreatment.
The original 45S5 bioglass has been already used in different materials for repairing bone defects in the jaw and orthopaedics. Bioactive glass grafts were originally developed for replacing ear bones and alveolar bone defects around teeth; the products used were based on particles rather than monolithic shape, i.e . PerioGlas ® and NovaBone ® . Micro and nano-particles have superior bioactive behaviours due to a larger specific surface area that allows a faster ion release. Bioactive coatings are likewise very important for metallic implants because they have the potential to improve their performance by providing strong bonding to the host bone and to the resin cement . Nevertheless, 45S5 bioglasses are applied also to non-permanent materials especially used in dentistry. BG-pastes are favourable for the treatment of dentin hypersensitivity , enamel demineralization and for tooth bleaching . Finally, bioactive glasses have satisfying characteristics as a scaffold material for bone tissue engineering, but the application of glass scaffolds for the load-bearing bone defects reparation is often limited by their low mechanical strength and fracture toughness.
Despite the excellent biological properties, mainly osteoblast proliferation and differentiation induced by the released ions by the material, bioglasses are brittle materials that are easily cracked. This low strength and fracture toughness prevents their use for load-bearing implants . The development of new glass compositions with improved mechanical properties is a challenging objective and the trend is to incorporate different elements to obtain better biological and physical characteristics. Crystallinity significantly changes the fracture characteristics of glasses. This opens the way for glass-ceramics as offerings with improved mechanical properties. On the other hand, the introduction of crystalline phases could decrease the bioactivity. Several attempts have been made to preserve the amorphous structure of the glass with the addition of silver, magnesium, strontium, boron, zinc, aluminium, fluoride, potassium, gallium, barium and zirconia. Addition of silver and boron have been investigated in order to improve the strength and develop antibacterial and antimicrobial materials; magnesium has stimulatory effects on the growth of new bony tissues ; calcium is shown to be responsible for osteoblast proliferation , while elements like zirconia improve the mechanical properties but decrease the bioactivity behaviour .
In recent years, bioactive glass particles have been introduced as fillers in conventional composites for tissue engineering, mixing them with polymers such as polylactic acid (PLA), polyglycolic acid (PGA) and their copolymer poly l (lactic- co -glycolic) acid (PLGA). Composite scaffolds for bone tissue engineering have been studied to obtain materials that impart better mechanical and physiological properties to the host tissue. Polymer/bioactive glass composite scaffolds show especially an increase in bioactivity which is achieved by the bioglass inclusion. The degree of bioactivity is adjustable by the volume of fraction, size, shape and arrangement of this inclusion. It has been shown that increased volume fraction and higher surface areas to volume ratio favour higher bioactivity; incorporation of fibres as fillers (instead of particles) enhances the mechanical properties. The dissolution of the bioactive glass should result in nucleation and growth of a crystalline HCA layer on the surface of the polymer scaffold, which should further affect the polymer degradation behaviour in addition to provide the required osteoconductivity. Thus, a combination of polymers and bioactive glass phases result in promising composite scaffolds for (bone) tissue engineering. Finally, it is clear that the chemistry and physical properties of the added polymer and bioactive glass have a significant incidence on mechanical properties and consequently in material degradation .
Several families of bioactive glasses have been more precisely investigated:
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Silicate-based glasses, like 45S5, are glasses where silica (SiO 2 ) is the classic network-former. The basic unit is the SiO 4 tetrahedron capable of sharing up to 4 oxygen atoms with other such tetrahedral units or other elements. Silicon has a charge of 4+.
- •
Phosphate-based glasses in the system CaO–Na 2 O–P 2 O 5 have the tetrahedral structure formed by PO 4 units and the phosphate group has a charge of 5 + . Therefore, they contain at least one terminal oxygen that limits connectivity and so the reactivity of the structure that gives unique dissolution properties in aqueous-based fluids for these types of glasses.
- •
Borate-based glasses are based on a B 2 O 3 network that can occur both in triangular and tetrahedral coordination but mostly in the triangular form especially vitreous compounds. Borate glasses show potential in bone regeneration owning to its complete conversion to apatite through a series of dissolution-precipitation reaction similar to those of 45S5 bioglass.
The purpose of this literature review is to assess the mechanical and biological properties of bioactive glasses used for dental and medical applications regarding their compositions.
2
Materials and methods
PRISMA guidelines for systematic review and meta-analysis have been used for this review manuscript . A literature search was performed using several electronic databases (PubMed, ScienceDirect) on articles published in the last 5 years, to identify the most recent developments on the subject. The research took place on 1st March 2016 in the Faculté d’Odontologie, Université Claude Bernard Lyon 1, Lyon, France. To be included, papers had to consist of both physical properties and biological properties or at least physical properties as these studies had to provide valid information in order to compare the various results obtained in the different studies. Language restrictions were not applied. Furthermore, these studies had to meet the following criteria:
- 1.
Bioactive glasses used in medicine.
- 2.
Evaluation of mechanical and biological properties.
The terms used in the search (in Title/Abstract) were as follows:
(“Bioglass*” AND “Biological properties”)
OR
(“Bioglass*” AND “Physical properties”).
Review articles and short communications were excluded. Two reviewers (FL and CV) screened accurately and independently all the titles and abstracts. The full texts of all the articles in accordance with the inclusion criteria (by consensus) were collected and reviewed. Also all the reference citations were screened for any relevant publications that might have been missed by the electronic search and that could be relevant for the current report. Finally, a consensus between the two readers was reached to determine which studies met the selection criteria.
2
Materials and methods
PRISMA guidelines for systematic review and meta-analysis have been used for this review manuscript . A literature search was performed using several electronic databases (PubMed, ScienceDirect) on articles published in the last 5 years, to identify the most recent developments on the subject. The research took place on 1st March 2016 in the Faculté d’Odontologie, Université Claude Bernard Lyon 1, Lyon, France. To be included, papers had to consist of both physical properties and biological properties or at least physical properties as these studies had to provide valid information in order to compare the various results obtained in the different studies. Language restrictions were not applied. Furthermore, these studies had to meet the following criteria:
- 1.
Bioactive glasses used in medicine.
- 2.
Evaluation of mechanical and biological properties.
The terms used in the search (in Title/Abstract) were as follows:
(“Bioglass*” AND “Biological properties”)
OR
(“Bioglass*” AND “Physical properties”).
Review articles and short communications were excluded. Two reviewers (FL and CV) screened accurately and independently all the titles and abstracts. The full texts of all the articles in accordance with the inclusion criteria (by consensus) were collected and reviewed. Also all the reference citations were screened for any relevant publications that might have been missed by the electronic search and that could be relevant for the current report. Finally, a consensus between the two readers was reached to determine which studies met the selection criteria.
3
Results
3.1
Study selection
A total of one hundred and nine abstracts were collected after an electronic database search with the selected terms ( Fig. 1 ). After the first screening, sixty-eight publications were excluded based on the title and abstract because they did not meet the inclusion criteria. The full texts of the forty-one remaining studies were read. Nineteen of them did not meet the inclusion criteria:
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Ag and Sr substituted bioactive glass for the investigation of antibacterial effects ;
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Focused on cells growth, proliferation and protein interactions ;
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Studies evaluating only the bioactivity and hydroxyl apatite (HA) formation ;
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General characterization and synthesis of bioglass powders ;
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Mechanical properties of a bioactive ceramic β-TCP .
The references of the twenty-two remaining publications were screened carefully for additional studies that might have been missed by the electronic search (no paper found). Finally, no other articles have been included in the present review.
3.2
Studies aim
All the twenty-two remaining articles were classified based on different scientific themes present in each of them and related to the influences on the mechanical/biological properties. These properties describe the reactions to physical forces applied directly to their surfaces. Mechanical properties occur as a result of the physical properties inherent to each material, and are determined through a series of standardized mechanical tests. For this reason, the methods used for determining the mechanical properties have also been listed. Moreover, the impact of polymers addition to the glass filler and the bioactivity identified with the different materials has been evaluated.
3.3
Testing objectives
Most of the articles selected describe the effects of one specific property. However, some authors investigated more than one test to provide a more complete characterization ( Table 1 ). In fact, two properties are studied in 8 articles and in one case three properties have been reported .
| Number of tests | Physical properties | Related articles |
|---|---|---|
| 1 | Compressive strength | |
| Tensile strength | ||
| Elastic modulus | ||
| Flexural strength | ||
| Knoop microhardness | ||
| Vicker’s hardness | ||
| 2 | Vicker’s hardness + elastic modulus | |
| Compressive strength + elastic modulus | ||
| Tensile strength + elastic modulus | ||
| 3 | Elastic modulus + tensile strength + compressive strength | |
3.4
Testing methodology
The universal testing machine, able to measure the tensile strength and the compressive strength of the materials is used in most of the articles (n = 14). In five studies, indentation hardness tests were used to calculate Vicker’s hardness and Elastic modulus. The Archimedean method was used in two studies to obtain flexural strength and elastic modulus. Just one paper used an Electro Force Biodynamic Test Instrument for the mechanical characterization of biomaterial specimens in contact with simulated body fluids (SBF) solution. The testing methods are detailed in Table 2 .
| Type of test | Related articles |
|---|---|
| Universal testing machine | |
| Indentation hardness test | |
| Ultrasonic method | |
| Archimedean method | |
| Electro force biodynamic test |
3.5
Compositional features, mechanical properties and applications
Considering all the twenty-two studies, ten of them are investigating the direct influence of different compositions of glasses on mechanical properties . Most of them are investigating the silicates system, only one is studying a porous silicate BG mixed with hydroxyapatite (HA). Regarding the final applications, they are divided into: bone tissue regeneration , tooth abrasion and both bone and dental application . The remaining twelve articles point out the effect given by polymers addition to different glass systems. The majority of them is still centred on Silicate systems except for two studies that investigate respectively HA/CaCO 3 and grounded mineral trioxide aggregates (MTA). These twelve articles are mostly focused on applying the material in scaffolds and composites for bone tissue engineering while, only two articles are dealing with dental field . The articles are listed in Table 3 .
| BG system | Composition features | Effect on mechanical properties | Application | Articles |
|---|---|---|---|---|
| Si–Ca–Na–P–K–Mg | Infiltrated with PCL | Improved elastic modulus and compressive strength | Hard tissue regeneration and bone tissue engineering | a |
| Infiltrated with PLA | ||||
| Si–Ca–Na–P | Addition of Ba | Improved flexural strength | Bone substitution | |
| Si–Ca–Na–P–K | BG + HA (80 wt%: 20 wt% ratio) | Improved Vicker’s hardness & elastic | Composites for bone tissue repair and regeneration | |
| Si–Ca | Mixed with PCL | Improved elastic modulus | Composite for tissue engineering | a |
| Si–Ca–Na–Al–P–Mg–Fe | Coated with P3HB | Improved compressive strength and compressive modulus increasing immersion time of the polymer, | Scaffolds for bone tissues engeneering | a |
| Si–Ca–P–Sr | Addition of PCL | Improved compressive strength and elastic modulus increasing Sr concentration and PCL addition | Composite for tissue engineering | a |
| Si–Ca–Na–P | Incorporated into dental adhesives | Reduction of Knoop microhardness values after prolonged DPBS storage | Dental restorative and bonding adhesive | a |
| Grounded MTA | ||||
| CaCO 3 | Addition of PLGA | Lower compressive and tensile Young’s modulus | Bone substitute material for orthopaedics | a |
| HA | ||||
| 45S5 | Improved Compressive strength, Compressive and Tensile Young’s modulus | |||
| ICIE4 | ||||
| Si–Ca–P | Increase Si content | Improved Young’s modulus with higher Si content | Bone regeneration | |
| Si–Ca–P | Addition of PLGA | Improved mechanical properties | Bone tissue engineering | a |
| Si–Ca–P | Mixed with PVA, chitosan and collagen | Improved compressive strength and compressive modulus for a 1:1 PVABG/ChiCol ratio | Commposite scaffolds for bone replacemet application | a |
| Si–Ca–Na | Addition of nitrogen | Improved microhardness & elastic modulus | Orthopaedic and dental | |
| Si–Ca–Na–P–F | Na 2 O content variation | Reduction of Vicker’s hardness linearly with increasing Na 2 O content | Air abrasion, tooth remineralization | |
| Si–Ca–Na–Sr–Zn | Mixed with PEGDMA | Improved in compressive strength and Young’s modulus values | BG composite hydrogels as bone graft substitutes in cancellous bone defects | a |
| Si–Ca–Na–P | Mixed with PDLLA | The mechanical properties were not significantly influenced | PDLLA/BG membranes for the treatment of periodontal defects | a |
| BG + HA | Addition of Al 2 O 3 | Improved compressive strength with increasing Al 2 O 3 | Orthopedic and dental | |
| Si–Ca–Na–P | Foaming sol–gel synthesis | Reduced compressive strength with increasing porosity | Scaffolds for bone tissues engeneering | |
| Si–Ca–Na–P | Thermal treated | Improved bone load-bearing capacity | Bone graft substitutes | |
| Si–Ca–Na–P | Increasing CaO/P 2 O 5 ratio | Improved elastic modulus | Prosthesis or bone implantation | |
| Nano Si–Ca–Na–P | Incorporated in dense collagen gels | Improved compressive modulus | Hydrogel scaffolds for bone tissue engineering | a |
| Si–Ca–Na–P–Ag | Scaffolds produced using the foam replication technique | Improved compressive strength of scaffolds | Scaffolds with therapeutic and antibacterial potential for bone tissue engineering | a |
| Si–Ca–Na–P | Addition of Na 2 O | Reduction of Vicker’s hardness with increasing Na 2 O content | Bone prostheses | |
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