Absorbable Biomaterials in Orthopaedic Surgery: The Extent of the Market Potential
Author: Paul Taylor - Consultant
The 20th century has witnessed the introduction of a variety of different major medical technological advances either through a step-by-step evolutionary process through existing products or through landmark or radical product innovations. The pace of this change has accelerated dramatically over the last two decades as advances in medical scientific research and knowledge provide opportunities for research and development into new and novel solutions to existing clinical conditions.
It is clear from a survey of literature on biomedical engineering that there is an increasing interest in absorbable biomaterials with specific biological properties and good biocompatibility profiles. Much of this interest has been stimulated by recent breakthroughs in tissue engineering techniques, where absorbable scaffold materials are used as a support matrix or as a substrate for the delivery of cultured cells or for three- dimensional tissue reconstruction. New applications are emerging for biomaterials in addition to traditional ones where a degradable material may be used on its own, as for bone fixation in orthopaedic practice, cavity filling materials and sutures in surgery or drug delivery systems in pharmacology as immediate examples.
Similarly, the ultimate aim of biomaterials as applied to fracture fixation is to restore the structural integrity of the damaged bone. The attainment of this objective is dependent upon a complex interplay of materials properties, device design, and physiologic requirements. Important considerations to be taken into account are the site and type of fracture, the possible operative approaches, the rapidity of bone healing, and the desired or feasible program of postoperative care. Specifically, the materials selection process must incorporate the chemical and mechanical demands of the biologic environment to achieve a functional outcome.
In addition, further research into different biomolecular engineering strategies have led to the development of a variety of synthetic and modified natural polymers aimed at reaching the highest level of compatibility in the physiological environment, i.e. optimal performance of function, low toxicity, convenient degradation rate and ideal tissue response. Among these, a new class of materials consisting of different hyaluronan derivatives promises to be useful in a whole range of clinical applications thanks to their varied biological properties. These new materials are obtained by chemical modification of purified hyaluronan consisting of the partial or total esterification of the carboxyl groups of this natural polymer.
Evaluating the Market Opportunities
HBS Consulting have determined that the total European market for absorbable and erodable orthopaedic biomaterials in 2003 has been valued at between $112.5 –118.0m. Market intelligence also suggests that the market for currently available absorbable and erodable orthopaedic biomaterials is growing at between 11-14% per annum. This is significantly higher than the traditional orthopaedic implant market at an estimated 5.5% per annum and is anticipated to continue growing at this rate for the foreseeable future.
Current State-of-the Art
In response to market demands and unmet clinical needs a considerable number of research projects are currently underway which promise to expand dramatically the indications and applications for absorbable biomaterials. One area of intense research activity is the use of biodegradable polymers for tissue engineering, which can be defined as the application of engineering principles to create devices for the study, restoration, modification, and assembly of functional tissues from native or synthetic sources. Candidate materials include natural polymers (fibrin, collagen, gelatin, hyaluronan), synthetic polymers (e.g., PolyLactic Acid (PLA), PolyGlyconate Acid (PGA), Poly-lactic acid/poly-glycolic acid (PLGA), ethylene oxide block copolymers, and inorganic materials (tricalcium phosphate, calcium carbonate, non-sintered hydroxyapatite).
A recent project (A Deschamps et al., Transactions of the Sixth World Biomaterials Congress, I (Minneapolis: Society for Biomaterials, 2000), 364) investigated the possibility of manufacturing biodegradable composites for use as bioactive matrices to guide and support tissue in growth. Composites were prepared using polyhydroxybutyrate (PHB), a naturally occurring ß-hydroxyacid linear polyester, and as much as 30% by volume of either hydroxyapatite (HA) or tricalcium phosphate (TCP). One of the goals was to achieve a reasonably homogeneous distribution of the HA/TCP particles in the PHB matrix, as this uniformity would provide an anchoring mechanism when the materials would be employed as part of an implant. The composites were successfully manufactured through a compounding and compression moulding process. It was observed that microhardness increased with an increase in bioceramic content for both the HA and TCP compounds.
Collaborative efforts with industrial and academic scientists at a variety of institutions are currently underway and include fabrication and testing of new polymeric and composite materials and cell culture and implantation studies. One of the areas of particular interest is in tissue engineering where several applications in orthopaedics have been identified. These include:
· Cell and Molecular Engineering of Bone Regeneration
· Bone and Cartilage Reconstruction
· Development of Bioengineered Tendons and Ligaments
The ‘tissue engineering’ approach to Anterior Cruciate Ligament (ACL) reconstruction uses absorbable scaffolds consisting of tissue-derived and/or synthetic materials to induce neoligament formation. This concept was originally developed for repair of other connective tissues including skin, bone, and cartilage. In contrast to permanent synthetic prostheses that lose strength with time, the mechanical behaviour of these implants should improve with time due to neoligament tissue development and remodelling.
Currently research is being carried out for example at the Chelsea and Westminister Hospital in London to create new specialised tissues grown from banks of undifferentiated pluripotent stem cells which can be genetically customised to individual recipients. The long-term plan of this research project is to create customised replacements for bone, cartilage, ligaments and muscle destroyed by illness or accident or weakened by old age. The same laboratory is conducting research into the development of a spinal implant to replace degenerative discs, which have become hopelessly abnormal due to inflammation. The replacement disc, which has a ceramic framework containing living bone and cartilage cell is, at the time of writing, being tested in the laboratory.
Issues and Challenges
Despite the recognised advantages to absorbable biomaterials there are a number of scientific and business challenges that need to be met. These include
Technical Problems Associated with Absorbable Medical Devices Restrains Market Development
Theoretically, absorbable materials are the best alternative for internal fixation of fractures because during the healing of bone lesions the absorbable device maintains the required fixation, decomposes gradually and the stresses are transferred gradually at the same time to the healing bone so that no stress shielding will occur. After healing the device can also be utilised in energy and protein metabolism. Absorbable surgical devices do not require a removal operation, which is of financial and psychological benefit and do not obscure the fracture site when taking X- rays. Despite these theoretical benefits associated with absorbable fixation devices there are a number of technical/medical problems, which have been identified. These include:
Technical problems associated with product performance
These include the inability of absorbables used in fracture repair to have sufficient mechanical strength to be load bearing. The consequence of this is that for the foreseeable future metal fixation devices will continue to be used for the fixation of complex fractures, long-bone fractures or fractures of stress bearing bone.
Technical problems relating to packaging
Because biodegradable polymers are hydrolytically unstable, the presence of moisture can degrade them in storage, during processing, and after device fabrication. In theory, the solution for hydrolysis instability is simple: eliminate the moisture and thus eliminate the degradation. However, because the materials are naturally hygroscopic, eliminating water and then keeping the polymer free of water are difficult to accomplish. The as-synthesised polymers have relatively low water contents, since any residual water in the monomer is used up in the polymerisation reaction. The polymers are quickly packaged after manufacture—generally double-bagged under an inert atmosphere or vacuum. The bag material may be polymeric or foil, but it must be highly resistant to water permeability. To minimise the effects of any moisture present, the polymers are typically stored in a freezer. Packaged polymers should always be at room temperature when opened to minimise condensation, and should be handled as little as possible at ambient atmospheric conditions. As expected, there is a relationship among biodegradation rate, shelf stability, and polymer properties. For instance, the more hydrophilic glycolide polymers are much more sensitive to hydrolytic degradation than are polymers prepared from the more hydrophobic lactide. Final packaging consists of placing the device in an airtight, moisture proof container. A desiccant is sometimes added to further reduce the effects of moisture.
Technical problems relating to sterilisation
Devices incorporating biodegradable polymers cannot be subjected to autoclaving, and must be sterilised by gamma or E-beam irradiation or by exposure to ethylene oxide (EtO) gas. There are certain disadvantages, however, to both irradiation and EtO sterilization. Irradiation, particularly at doses above 2 Mrd, can induce significant degradation of the polymer chain, resulting in reduced molecular weight as well as influencing final mechanical properties and degradation times. Polyglycolide, poly(lactide), and poly(dioxanone) are especially sensitive to ionizing radiation, and these materials are usually sterilised by EtO for device applications. Because the highly toxic EtO can present a safety hazard, great care is required to ensure that all the gas is removed from the device before final packaging. The temperature and humidity conditions should also be considered when submitting devices for sterilisation. Temperatures must be kept below the glass-transition temperature of the polymer to prevent the part geometry from changing during sterilisation. If necessary, parts can be kept at 0°C or lower during the irradiation process.
Relatively High Cost of Orthopaedic Absorbables Compared with Traditional Materials Restrains Market Growth
During the initial introductory phase of new and novel absorbable fixation devices product pricing were between 10 percent to 400 percent more than their equivalent metal fixation devices. In addition operating room managers, on whose shoulders the duty of purchasing absorbable fixation devices most often falls, have found it difficult to compare the ultimate costs of absorbable and metal fixation devices and consequently assumed that these new technologies were more expensive. Recently however volume discounts have helped ameliorate this problem as a result of what healthcare purchasers refer to as productive bidding wars by simultaneously bringing several absorbable implant makers into the purchasing process. With this strategy, healthcare purchasers stated that “you can rapidly get the price down to something reasonable,” and “our ACL screws now cost the same as the metal ACL screws we used to use.”
Medico Problems Associated with Absorbable Medical Devices Restrains Market Development
Resistance to change amongst clinical professionals
Unfortunately not every orthopaedic surgeon favours the new absorbable fixation-device technology. Many are waiting until scientific data accumulate to prove that the absorbable fixation devices do disappear, to the benefit of the patient, and that money is saved through their use. One of the most compelling arguments used for the employment of absorbable fixation devices is that if a soft tissue attachment must be redone, metal fixation devices need to be removed. However, many orthopaedic surgeons feel that the frequency with which that problem occurs is too low to justify switching to a new technology that is more expensive.
Rapid learning curve associated with surgical technique
There are number of important practical considerations and difficulties with the traditional fracture fixation surgical techniques. These include:
Absorbable fixation devices require their own types of drivers for insertion, and if plates are being formed, the polymer material must be heated; it cannot be bent when cold.
Attachment-site tunnels must be drilled (tapped) into the bone to the full length of the absorbable anchors and screws because, unlike metal, they cannot cut bone. In addition some surgeons have reported that they have difficulties inserting absorbables and once inserted, they are not always secure. For example absorbable screws frequently break on insertion or as a result of the lower mechanical strength of absorbable screws compared with metallic screws. The screw heads from screws made from biomaterials frequency bur and the surgeon losses purchase between the screwdriver. This often results in the screwdriver tip spinning should the surgeon attempt to over tighten the screw and making it difficult for any unplanned removal of the screw..
Despite these issues HBS Consulting believes that the future is bright for absorbable biomaterials as we anticipate that there will be significant advances made into fundamental scientific research, product development and the market introduction of new and novel products. This will ensure that there will be a growing list of surgical applications and the more extensive use of newer products for existing applications.
HBS Consulting predict that gaining and maintaining technological advantage in absorbable biomaterials will be a key constituent of the marketing and strategic planning process, for those companies listed in Table 1 or companies who have expressed an interest in these market segments, to ensure they retain their competitive edge and gain new business from the opportunities that are undoubtedly taking place.
Table 1.
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