Understanding the materials science of medical devices on a molecular scale contributes to a better understanding of their interaction with the human body and aids future developments in form and function. Mark Turner of Medical Engineering Technologies summarises some of the techniques employed in chemical analysis, particularly of surfaces.
I’ve got a great idea! What we really need is a urethral catheter that slides so smoothly you can’t even feel it. It should be totally resistant to bacterial growth, very, very flexible and of course it won’t kink. Or maybe we should develop an artificial hip in a material that is so well integrated into the body, that a year after the operation, it is indistinguishable from real bone. Ideas are great, but what is really involved in getting these great ideas into service? Good materials analysis will certainly help them along the way. Here we look at some of the analyses used in functional and biocompatibility testing.
Medical devices depend on their physical, chemical and surface properties to deliver their actions and deliver them safely in vivo. These properties are dictated, in large part, by the underlying chemistry of a material. A device developer may go to a polymer or other material supplier with a wish list of properties such as good biocompatibility, stability in sterilisation, conformation at body temperature, easy bonding between the polymer and another part of the device made from another material, and so on. Or, a newly developed material may have properties that can be applied to medical devices.
Medical device engineers can keep up to date with new materials, for example, by following trade publications or by maintaining links with their local university. Many new materials and devices are developed in conjunction with a research establishment. There are also materials identified independently by these institutions, often with spin off companies being set up to exploit the possibilities. Some materials such as hydroxyapatite (HA), a crystalline form of hydroxy calcium phosphate, which is used to improve osseointegration1
of implants, have evolved through clinical science. This class of mineral was first described by Werner,2
who was born in 1786. These minerals were exploited in dental medicine from the early 1900s and the first documented use of calcium phosphate in human bone repair was in 1920.3
Much academic progress was made in the 1970s,4
with the first use of a HA coating on femoral hip stems in 1985.5
The research and development of the material in biomedical applications continues apace to this day.
Engineers are mainly interested in the physical properties of a material. A medical device developer has to be interested in other factors as well such as the biocompatibility of a material, how it performs during its period of use, how it supports its shelf life and whether there will be any breakdown in vivo. Some of these properties can be predicted as a material is developed. For example, polyetheretherketone (PEEK) was identified as a part of a family of inert rigid materials from its chemical structure. However, often properties must be discovered or at least verified empirically.
Analysis of materials is important during device development and production and all materials should be characterised in their final form. The chemical signature of the material, specified in development, can be used to ensure that the future batches of the material or products, irrespective of supplier, are identical. All additives, including plasticisers, preservatives, impurities, ultraviolet protection additives, lubricants and antimicrobials, should be included, because they effectively change a material’s chemical composition and therefore its chemical and physical interaction with the body.
Often it is the surface of a medical device that is of crucial importance. This is where biocompatibility is generally decided, integration with body parts, uptake or release of substances. Even the topology of the surface has an influence. This is reflected in chemical analysis often being targeted on material surfaces. Much biocompatibility testing is done with extracts obtained by soaking intact devices with a selection of solvents. This process leaches out mobile materials from the surface and it is this leachate that is used in elution cytotoxicity, together with other biocompatibility tests and in chemical analysis.
A wide variety of chemical analyses are available for the clarification of material structures and components. Table I lists the chemical tests associated with biocompatibility as described in ISO 10993-18:2005 Biological Evaluation of Medical Devices, Part 18: Chemical Characterisation of Materials. Additional parts of this standard that could be of interest when performing material analyses are listed in Table II. US Pharmacopeia (USP) Class 6 classification that a material is biocompatible is useful information to have when beginning work on developing a new medical device, but it is superseded by ISO 10993, which requires testing on the finished product.
There is a wide array of ASTM6
standards pertaining to implants; they specify material compositions, corrosion resistance and passivation of metals. There is also US Food and Drug Administration Guidance7
that gives a similar range of testing for resorbable implants; this document also describes physical testing and life cycle testing.
Tissue engineered products
ASTM International has produced a number of test method documents for characterising scaffold and functional materials. These include alginates, ceramics, collagen, chitosan, hyaluronan, and a more general test method8
for the characterisation of scaffolds.
Drug delivery devices
Nanoparticles are an area of particular concern in drug delivery. Guidance and standard test methods are yet to crystallise in this area. But, some drug delivery devices have been around for long time, including nebulisers, anaesthetic machines and needles and specific standards are often in force for these items. These can be found by searching the International Organisation for Standardisation’s and ASTM International’s websites. Also, for these devices pharmacopeia monographs and standards such as USP Chapter 724, which deals with drug release calibration, can be relevant. There is one for measuring the release of active substances from transdermal patches.9
Less invasive devices
Chemical analysis is also important for less invasive devices, especially if they have coatings or a surface activity such as antimicrobial properties. For example, poly(vinyl chloride) tubing has many applications in the medical device market. Often it is specified because it softens at body temperature, but does not collapse. This property is partly controlled mechanically by tubing diameter and wall thickness, but hoop strength and softening are largely controlled by fillers and plasticisers. These additives need to be accurately defined in development and verified batch to batch in production.
Material analysis is part of the understanding of the performance, lifecycle and structure of any medical device. It is an important aid to development and essential to quality control of production. With tight costing and the increasing competitiveness within the industry, material analysis helps to avoid additional costs being incurred, for example, from the lost production due to the use of unsuitable materials delivered either by mistake or due to a process change that has not been documented. This could lead to the possibility of adverse reactions and/or rejection of the device by the patient and a possible product recall. Having a correct chemical signature for the correct materials used for the device allows a replacement material to be employed without the expense of full biocompatibility testing.
1. B. Sandán et al., "Hydroxyapatite Coating Improves Fixation of Pedical Screws,” British Editorial Society of Bone and Joint Surgery, 84-B, 3 (2002), web.jbjs.org.uk/cgi/reprint/84-B/3/387.pdf.
2. A.G.Werner, "Short Classification and Description of the Various Rocks” (1786).
3. F.H. Albee, "Studies in Bone Growth: Triple Calcium Phosphate as a Stimulus to Osteogenesis,” Ann. Surg., 71, 1, 32–39 (1920).
4. L.L. Hench, J. Wilson, "An Introduction to Bioceramics,” World Scientific Publishing Co. Pte. Ltd, Singapore (1993).
5. R.J. Furlong, J.F. Osborn, "Fixation of Hip Prostheses by Hydroxyapatite Ceramic Coatings,” J. Bone and Joint Surg.,
73-B, 3, 741–745 (1991).
6. ASTM International www.astm.org
7. Guidance document for Testing Biodegradable Polymer Implant Devices, www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080265.htm.
8. ASTM F2150-08, Standard Guide for Characterisation and Testing of Biomaterial Scaffolds Used in Tissue-Engineered Medical Products.
9. Transdermal Delivery Systems – General Drug Release Standards,
Mark Turner is Sales Director at
Medical Engineering Technologies Ltd,
Yew Tree Studios, Stone Street, Stanford North, Ashford TN25 6DH, UK,
tel. +44 (0)8454 588 924,
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