Bioresorbable metal

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Bioresorbable (also called biodegradable or bioabsorbable) metals are metals or their alloys that degrade safely within the body. [1] The primary metals in this category are magnesium-based [2] [3] and iron-based alloys, [4] although recently zinc has also been investigated. [5] [6] Currently, the primary uses of bioresorbable metals are as stents for blood vessels (for example bioresorbable stents) and other internal ducts.

Contents

Background

Although bioabsorbable polymers and other materials have come into widespread use in recent years, degradable metals have not yet had the same success in the medical industry.

Driving force for development

The driving force behind the development of bioresorbable metals is primarily due to their ability to provide metal-like mechanical properties while degrading safely in the body. [1] This is especially relevant in orthopaedic applications, where although many surgeries only require implants to provide temporary support (allowing the surrounding tissue to heal), the majority of current bio-metals are permanent (e.g. stainless steel, titanium). Degradation of the implant means that intervention or secondary surgery will not be necessary to remove the material at the end of its functional life, providing significant savings in both cost and time for the patient and health care system. In addition, the corrosion products of current bio-metals (which will still corrode in the body to some degree) can generally not be considered biocompatible.

Potential applications

There are a number of applications for biodegradable metals, including cardiovascular implants (i.e. stents) and orthopedics. It is in this latter category where these materials offer the greatest potential. Bioresorbable metals are able to withstand loads that would destroy any currently available polymers, and offer much greater plasticity than bioceramics, which are brittle and prone to fracture. A well-designed implant could provide the exact mechanical support needed for different areas (through alloying and metal working), and load would be transferred to the surrounding tissue over time, letting it heal and reducing the effects of stress shielding. [7] A summary of the primary benefits and drawbacks of magnesium biomaterials has been provided by Kirkland. [2]

Considerations and issues facing bioresorbable metal development

Changing shape over time

It is the same advantage that bioresorbable metals possess over non-degradable current materials, their biodegradability, that poses the greatest challenges to their development and wider use. The degradable nature of any implant means that their shape and thus mechanical properties will change through its lifetime. This means that lifecycle analysis must be performed on any implant, especially one designed for orthopedic applications where failure could result in death.

Lack of standards

Current standards for corrosion of metals have been found to not apply well to bioresorbable metals during in vitro testing. [8] This is a significant problem as the majority of tests performed in the research community are a mix of other standards from both the biomedical and the engineering (e.g. corrosion) communities, often making comparison between results difficult.

Corrosion Product Toxicity

Even though all elements in a bioresorbable metal may themselves be considered biocompatible, the morphology and elemental makeup (or combination of elements) of the degradation products may cause adverse reactions in the body. In addition, the rapid evolution of hydrogen gas that is concomitant with Mg-alloy degradation may cause addition problems in vivo. [9] It is therefore crucial to intricately understand the corrosion of each implant and the products that are release, in light of their toxicity and the likelihood of inflammation. The majority of studies in the literature have focused on elements that are known to be biocompatible or abundant in the body, such as calcium [10] [11] and zinc. [12]

Potential bioresorbable metal candidates

Although all metals will degrade and eventually disappear inside the body through the processes of corrosion and wear, true bioresorbable metals must have an appreciable degradation rate to allow the implant to be absorbed in a practical amount of time in reference to their application. Also, any degradation product would have to be safely metabolized or excreted by the body to avoid toxicity and inflammation.

Magnesium

Perhaps the most widely investigated material in this category, magnesium was originally investigated as a potential biomaterial in 1878 when it was used by physician Edward C. Huse in wire form as a ligature to stop bleeding. [13] Development continued into the 1920s, after which Mg-based biomaterials fell out of general investigation due to their poor performance (likely due to impurities in the alloys drastically increasing corrosion). It was not until the late 1990s that interest started to pick up again, Mg has a density close to that of bone and is absorbed by the body .Mg is of interest for orthopedic applications due to its relatively low cost, high specific strength, and near-bone elastic modulus, which avoids stress shielding and allows uniform distribution of tissue stress [14] [15]

Currently, most research on Mg is focused on reducing and controlling the rate of degradation, with many alloys corroding too rapidly (in vitro) for any practical application. [7] [16]

Iron

The majority of iron-based alloy research has been focused on cardiovascular applications, such as stents. [17] However this area receives much less interest in the research community than Mg-based alloys.[ citation needed ]

Zinc

To date little work has been published on the use of a primarily zinc-based biomaterial, with corrosion rates found to be very low and zinc within a tolerable toxicity range [6] [7] .Furthermore, Pure Zn has poor mechanical behavior, with a tensile strength of around 100–150 MPa and an elongation of 0.3–2%, which is far from reaching the strength required as an orthopedic implant material (tensile strength is more than 300 MPa, elongation more than 15%). Alloy and composite fabrication have proven to be excellent ways to improve the mechanical performance of Zn. [18]

Biodegradable bulk metallic glasses

Although strictly speaking a side-category, a related, relatively new area of interest has been the investigation of bioabsorbable metallic glass, with a group at UNSW currently investigating these novel materials. [19]

Related Research Articles

<span class="mw-page-title-main">Magnesium</span> Chemical element with atomic number 12 (Mg)

Magnesium is a chemical element; it has symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals it occurs naturally only in combination with other elements and it almost always has an oxidation state of +2. It reacts readily with air to form a thin passivation coating of magnesium oxide that inhibits further corrosion of the metal. The free metal burns with a brilliant-white light. The metal is obtained mainly by electrolysis of magnesium salts obtained from brine. It is less dense than aluminium and is used primarily as a component in strong and lightweight alloys that contain aluminium.

<span class="mw-page-title-main">Stent</span> Type of medical device

In medicine, a stent is a tube usually constructed of a metallic alloy or a polymer. It is inserted into the lumen of an anatomic vessel or duct to keep the passageway open. Stenting refers to the placement of a stent. The word "stent" is also used as a verb to describe the placement of such a device, particularly when a disease such as atherosclerosis has pathologically narrowed a structure such as an artery.

<span class="mw-page-title-main">Polymer degradation</span> Alteration in the polymer properties under the influence of environmental factors

Polymer degradation is the reduction in the physical properties of a polymer, such as strength, caused by changes in its chemical composition. Polymers and particularly plastics are subject to degradation at all stages of their product life cycle, including during their initial processing, use, disposal into the environment and recycling. The rate of this degradation varies significantly; biodegradation can take decades, whereas some industrial processes can completely decompose a polymer in hours.

<span class="mw-page-title-main">Biocompatibility</span> Biologically compatible substance

Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoing development of insights into how biomaterials interact with the human body and eventually how those interactions determine the clinical success of a medical device. Modern medical devices and prostheses are often made of more than one material so it might not always be sufficient to talk about the biocompatibility of a specific material.

<span class="mw-page-title-main">Polycaprolactone</span> Chemical compound

Polycaprolactone (PCL) is a synthetic, semi-crystalline, biodegradable polyester with a melting point of about 60 °C and a glass transition temperature of about −60 °C. The most common use of polycaprolactone is in the production of speciality polyurethanes. Polycaprolactones impart good resistance to water, oil, solvent and chlorine to the polyurethane produced.

<span class="mw-page-title-main">Polydioxanone</span>

Polydioxanone or poly-p-dioxanone is a colorless, crystalline, biodegradable synthetic polymer.

<span class="mw-page-title-main">Magnesium alloy</span> Mixture of magnesium with other metals

Magnesium alloys are mixtures of magnesium with other metals, often aluminium, zinc, manganese, silicon, copper, rare earths and zirconium. Magnesium alloys have a hexagonal lattice structure, which affects the fundamental properties of these alloys. Plastic deformation of the hexagonal lattice is more complicated than in cubic latticed metals like aluminium, copper and steel; therefore, magnesium alloys are typically used as cast alloys, but research of wrought alloys has been more extensive since 2003. Cast magnesium alloys are used for many components of modern cars and have been used in some high-performance vehicles; die-cast magnesium is also used for camera bodies and components in lenses.

<span class="mw-page-title-main">Drug-eluting stent</span> Medical implant

A drug-eluting stent (DES) is a tube made of a mesh-like material used to treat narrowed arteries in medical procedures both mechanically and pharmacologically. A DES is inserted into a narrowed artery using a delivery catheter usually inserted through a larger artery in the groin or wrist. The stent assembly has the DES mechanism attached towards the front of the stent, and usually is composed of the collapsed stent over a collapsed polymeric balloon mechanism, the balloon mechanism is inflated and used to expand the meshed stent once in position. The stent expands, embedding into the occluded artery wall, keeping the artery open, thereby improving blood flow. The mesh design allows for stent expansion and also for new healthy vessel endothelial cells to grow through and around it, securing it in place.

<span class="mw-page-title-main">Biomaterial</span> Any substance that has been engineered to interact with biological systems for a medical purpose

A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose – either a therapeutic or a diagnostic one. The corresponding field of study, called biomaterials science or biomaterials engineering, is about fifty years old. It has experienced steady growth over its history, with many companies investing large amounts of money into the development of new products. Biomaterials science encompasses elements of medicine, biology, chemistry, tissue engineering and materials science.

Many opportunities exist for the application of synthetic biodegradable polymers in the biomedical area particularly in the fields of tissue engineering and controlled drug delivery. Degradation is important in biomedicine for many reasons. Degradation of the polymeric implant means surgical intervention may not be required in order to remove the implant at the end of its functional life, eliminating the need for a second surgery. In tissue engineering, biodegradable polymers can be designed such to approximate tissues, providing a polymer scaffold that can withstand mechanical stresses, provide a suitable surface for cell attachment and growth, and degrade at a rate that allows the load to be transferred to the new tissue. In the field of controlled drug delivery, biodegradable polymers offer tremendous potential either as a drug delivery system alone or in conjunction to functioning as a medical device.

Stress shielding is the reduction in bone density (osteopenia) as a result of removal of typical stress from the bone by an implant. This is because by Wolff's law, bone in a healthy person or animal remodels in response to the loads it is placed under. It is possible to mention the elastic modulus of magnesium compared to titanium, stainless steel, iron, or zinc, which makes it further analogous to the natural bone of the body and prevents stress shielding phenomena. Porous implantation is one typical alleviation method.

Nitinol biocompatibility is an important factor in biomedical applications. Nitinol (NiTi), which is formed by alloying nickel and titanium, is a shape-memory alloy with superelastic properties more similar to that of bone, when compared to stainless steel, another commonly used biomaterial. Biomedical applications that utilize nitinol include stents, heart valve tools, bone anchors, staples, septal defect devices and implants. It is a commonly used biomaterial especially in the development of stent technology.

<span class="mw-page-title-main">Bioceramic</span> Type of ceramic materials that are biocompatible

Bioceramics and bioglasses are ceramic materials that are biocompatible. Bioceramics are an important subset of biomaterials. Bioceramics range in biocompatibility from the ceramic oxides, which are inert in the body, to the other extreme of resorbable materials, which are eventually replaced by the body after they have assisted repair. Bioceramics are used in many types of medical procedures. Bioceramics are typically used as rigid materials in surgical implants, though some bioceramics are flexible. The ceramic materials used are not the same as porcelain type ceramic materials. Rather, bioceramics are closely related to either the body's own materials or are extremely durable metal oxides.

<span class="mw-page-title-main">Bioresorbable stent</span> Medical stent that dissolves or is absorbed by the body

A bioresorbable stent is a tube-like device (stent) that is used to open and widen clogged heart arteries and then dissolves or is absorbed by the body. It is made from a material that can release a drug to prevent scar tissue growth. It can also restore normal vessel function and avoid long-term complications of metal stents.

Bioresorbablemetallic glass is a type of amorphous metal, which is based on the Mg-Zn-Ca ternary system. Containing only elements which already exist inside the human body, namely Mg, Zn and Ca, these amorphous alloys are a special type of biodegradable metal.

<span class="mw-page-title-main">Surface modification of biomaterials with proteins</span>

Biomaterials are materials that are used in contact with biological systems. Biocompatibility and applicability of surface modification with current uses of metallic, polymeric and ceramic biomaterials allow alteration of properties to enhance performance in a biological environment while retaining bulk properties of the desired device.

<span class="mw-page-title-main">Titanium biocompatibility</span>

Titanium was first introduced into surgeries in the 1950s after having been used in dentistry for a decade prior. It is now the metal of choice for prosthetics, internal fixation, inner body devices, and instrumentation. Titanium is used from head to toe in biomedical implants. One can find titanium in neurosurgery, bone conduction hearing aids, false eye implants, spinal fusion cages, pacemakers, toe implants, and shoulder/elbow/hip/knee replacements along with many more. The main reason why titanium is often used in the body is due to titanium's biocompatibility and, with surface modifications, bioactive surface. The surface characteristics that affect biocompatibility are surface texture, steric hindrance, binding sites, and hydrophobicity (wetting). These characteristics are optimized to create an ideal cellular response. Some medical implants, as well as parts of surgical instruments are coated with titanium nitride (TiN).

Materials that are used for biomedical or clinical applications are known as biomaterials. The following article deals with fifth generation biomaterials that are used for bone structure replacement. For any material to be classified for biomedical applications, three requirements must be met. The first requirement is that the material must be biocompatible; it means that the organism should not treat it as a foreign object. Secondly, the material should be biodegradable ; the material should harmlessly degrade or dissolve in the body of the organism to allow it to resume natural functioning. Thirdly, the material should be mechanically sound; for the replacement of load-bearing structures, the material should possess equivalent or greater mechanical stability to ensure high reliability of the graft.

Titanium foams exhibit high specific strength, high energy absorption, excellent corrosion resistance and biocompatibility. These materials are ideally suited for applications within the aerospace industry. An inherent resistance to corrosion allows the foam to be a desirable candidate for various filtering applications. Further, titanium's physiological inertness makes its porous form a promising candidate for biomedical implantation devices. The largest advantage in fabricating titanium foams is that the mechanical and functional properties can be adjusted through manufacturing manipulations that vary porosity and cell morphology. The high appeal of titanium foams is directly correlated to a multi-industry demand for advancement in this technology.

References

  1. 1 2 Kirkland, N; Birbilis N (2013). Magnesium Biomaterials: Design, Testing and Best Practice. New York: Springer. ISBN   978-3-319-02123-2 . Retrieved 26 November 2013.
  2. 1 2 Kirkland, N. T. (2012). "Magnesium biomaterials: Past, present and future". Corrosion Engineering, Science and Technology. 47 (5): 322–328. doi:10.1179/1743278212Y.0000000034. hdl: 10069/29852 . S2CID   135864605.
  3. ↑ Saberi, A.; Bakhsheshi-Rad, H.R.; Karamian, E.; Kasiri-Asgarani, M.; Ghomi, H. (2020). "Magnesium-graphene nano-platelet composites: Corrosion behavior, mechanical and biological properties". Journal of Alloys and Compounds. 821: 153379. doi:10.1016/j.jallcom.2019.153379. S2CID   214172320.
  4. ↑ Peuster, M.; Wohlsein, P.; Brügmann, M.; Ehlerding, M.; Seidler, K.; Fink, C.; Brauer, H.; Fischer, A.; Hausdorf, G. (2001). "A novel approach to temporary stenting: Degradable cardiovascular stents produced from corrodible metal---results 6-18 months after implantation into New Zealand white rabbits". Heart. 86 (5): 563–569. doi:10.1136/heart.86.5.563. PMC   1729971 . PMID   11602554.
  5. ↑ Kong, Lingyun; Heydari, Zahra; Lami, Ghadeer Hazim; Saberi, Abbas; Baltatu, Madalina Simona; Vizureanu, Petrica (2023-07-03). "A Comprehensive Review of the Current Research Status of Biodegradable Zinc Alloys and Composites for Biomedical Applications". Materials. 16 (13). MDPI AG: 4797. Bibcode:2023Mate...16.4797K. doi: 10.3390/ma16134797 . ISSN   1996-1944. PMC   10343804 . PMID   37445111.
  6. 1 2 Vojtěch, D.; Kubásek, J.; Šerák, J.; Novák, P. (2011). "Mechanical and corrosion properties of newly developed biodegradable Zn-based alloys for bone fixation". Acta Biomaterialia. 7 (9): 3515–3522. doi:10.1016/j.actbio.2011.05.008. PMID   21621017.
  7. 1 2 3 Ibrahim, H.; Esfahani, S. N.; Poorganji, B.; Dean, D.; Elahinia, M. (January 2017). "Resorbable bone fixation alloys, forming, and post-fabrication treatments". Materials Science and Engineering: C. 70 (1): 870–888. doi: 10.1016/j.msec.2016.09.069 . PMID   27770965.
  8. ↑ Witte, F.; Fischer, J.; Nellesen, J.; Crostack, H. A.; Kaese, V.; Pisch, A.; Beckmann, F.; Windhagen, H. (2006). "In vitro and in vivo corrosion measurements of magnesium alloys". Biomaterials. 27 (7): 1013–1018. doi:10.1016/j.biomaterials.2005.07.037. PMID   16122786.
  9. ↑ Kuhlmann, J.; Bartsch, I.; Willbold, E.; Schuchardt, S.; Holz, O.; Hort, N.; Höche, D.; Heineman, W. R.; Witte, F. (2012). "Fast escape of hydrogen from gas cavities around corroding magnesium implants" (PDF). Acta Biomaterialia. 9 (10): 8714–21. doi:10.1016/j.actbio.2012.10.008. PMID   23069319.
  10. ↑ Kirkland, N. T.; Birbilis, N.; Walker, J.; Woodfield, T.; Dias, G. J.; Staiger, M. P. (2010). "In-vitro dissolution of magnesium-calcium binary alloys: Clarifying the unique role of calcium additions in bioresorbable magnesium implant alloys". Journal of Biomedical Materials Research Part B: Applied Biomaterials. 95B (1): 91–100. doi:10.1002/jbm.b.31687. PMID   20725953.
  11. ↑ Cao, J. D.; Martens, P.; Laws, K. J.; Boughton, P.; Ferry, M. (2013). "Quantitativein vitroassessment of Mg65Zn30Ca5degradation and its effect on cell viability". Journal of Biomedical Materials Research Part B: Applied Biomaterials. 101B (1): 43–49. doi:10.1002/jbm.b.32811. PMID   22997106.
  12. ↑ Brar, H. S.; Platt, M. O.; Sarntinoranont, M.; Martin, P. I.; Manuel, M. V. (2009). "Magnesium as a biodegradable and bioabsorbable material for medical implants". JOM. 61 (9): 31. Bibcode:2009JOM....61i..31B. doi:10.1007/s11837-009-0129-0. S2CID   40436409.
  13. ↑ Huse, Edward C. (1878). "A New Ligature?". Chicago Medical Journal and Examiner. 37 (2): 171–172. PMC   9838909 . PMID   37617179.
  14. ↑ Saberi, A.; Bakhsheshi-Rad, H.R.; Karamian, E.; Kasiri-Asgarani, M.; Ghomi, H. (2020). "Magnesium-graphene nano-platelet composites: Corrosion behavior, mechanical and biological properties". Journal of Alloys and Compounds. 821. Elsevier BV: 153379. doi:10.1016/j.jallcom.2019.153379. ISSN   0925-8388. S2CID   214172320.
  15. ↑ Liu, JunRu; Wang, XueYi; Saberi, Abbas; Heydari, Zahra (2023). "The effect of Co-encapsulated GNPs-CNTs nanofillers on mechanical properties, degradation and antibacterial behavior of Mg-based composite". Journal of the Mechanical Behavior of Biomedical Materials. 138. Elsevier BV: 105601. doi:10.1016/j.jmbbm.2022.105601. ISSN   1751-6161. PMID   36493612. S2CID   254343106.
  16. ↑ Kirkland, N. T.; Lespagnol, J.; Birbilis, N.; Staiger, M. P. (2010). "A survey of bio-corrosion rates of magnesium alloys". Corrosion Science. 52 (2): 287. doi:10.1016/j.corsci.2009.09.033.
  17. ↑ Moravej, M.; Mantovani, D. (2011). "Biodegradable Metals for Cardiovascular Stent Application: Interests and New Opportunities". International Journal of Molecular Sciences. 12 (7): 4250–4270. doi: 10.3390/ijms12074250 . PMC   3155349 . PMID   21845076.
  18. ↑ Kong, Lingyun; Heydari, Zahra; Lami, Ghadeer Hazim; Saberi, Abbas; Baltatu, Madalina Simona; Vizureanu, Petrica (2023-07-03). "A Comprehensive Review of the Current Research Status of Biodegradable Zinc Alloys and Composites for Biomedical Applications". Materials. 16 (13). MDPI AG: 4797. Bibcode:2023Mate...16.4797K. doi: 10.3390/ma16134797 . ISSN   1996-1944. PMC   10343804 . PMID   37445111.
  19. ↑ University of New South Wales (2010). "BMGs for Electronic, Biomedical and Aerospace Applications". Archived from the original on 5 January 2013. Retrieved 7 January 2013.
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