Medical trends over time have led to recent considerations for new and innovative possibilities for enhancing bone healing and stability, while reducing adverse morbidities associated with existing treatment modalities that utilise metallic surgical implants. Ideas about fully biodegradable substances for enhanced tissue healing have been presented during the modern era of reconstructions, based on surgical procedures utilising implants.
Natural and synthetic origin substances of many types were tried during the period prior to 1925. To achieve mechanically stable fixation of bone fractures, most found it necessary to use metallic alloys. Experiences within marine, aerospace and food applications led to a generally shared opinion; that iron (stainless steels) and cobalt (Stellites) based alloys were more acceptable compared to other systems such as silver, gold or platinum alloys. The central reasons for the selection of these particular iron and cobalt-based alloys included availability in 'high technology' reasonable cost forms, plus a combination of relative inertness and enough strength for the intended application.
Metallico, ceramics and polymerics: a history
These alloys were predominating through the 1950s until the introduction of reactive group alloys, primarily titanium based. With the discipline focusing on biomaterials for surgical implants in the 1970s, many different materials were reconsidered, leading to the fabrication of specialised biomaterials for bone fixation during healing. A wide range of ceramics (alumina, zirconia, titania), polymerics (acrylic, polyethylenes, polyesters) and combinations of these materials were evaluated.
Again, biotolerant type alloy biomaterials were continued for most applications associated with treatments of load-bearing bone regions.
During the 1980s, the surface-modified bioactive biomaterials found greater numbers of applications, with partial biodegradation of the implanted device part of the healing process. Applications of calcium phosphate compounds, normally plasma sprayed onto metallic surfaces as a coating, were considered to be an advantage for bone healing plus longer-term biointegration for force transfer and functional stability. During this decade and the 1990s, many proposed fibre-reinforced polymeric composites as alternatives to metallics. For the most part, emphasis on non-metallic composites focused on the biotolerant forms of biomaterials.
Advances in the science and technology of biologically derived substances gave opportunities for enhancing tissue healing. The maturity of specialised macromolecular forms such as bone morphogenic protein (BMP) and many other mitogenic and morphogenic substances resulted in re-evaluation of possibilities for partially or fully biodegradable structures for surgical implants.
Over the same period industrial-grade synthetic materials were evolving to biomaterials for surgical implants, engineering mechanics was being applied to physiological systems and implant reconstructions of bone. Multiple designs were considered for fixing and stabilising fractured bones during healing and once again, the relative inertness combined with biomechanical properties (modulus, strength, toughness) and processability led to the selection of many different designs as plates, screws, rods and wires for internal fixation, plus many forms that interconnected bone and fixator through the soft tissues.
Proponents of many specialised forms and surgical techniques evolved and in most situations metallics were continued for device biomaterials utilised for load bearing device construction. In part because of the extensive use of implants associated with bone, attention was focused on how best to attach to and stabilise various types of lesion sites where implant procedures were indicated.
The basic science of biomechanics evolved to describe the biomechanical conditions of bone function and conditions resulting in normal functional stability versus trauma and disuse atrophy.
During this period when metallic components were, or were not integrated along the implant-to-bone interface, conditions of longer-term bone remodelling were identified specific to biomaterial (substance of construction) and biomechanical (design shape and size) properties. Some of these conditions were adverse.
Standardisation and safety issues
In the 1990s, individuals from academic, industry and professional societies; the US Food and Drug Administration; National Institutes of Health and National Institute for Standards and Technology; and the American Society for Testing and Materials (ASTM) committee F04 developed activities to organise consensus standards on tissue-engineered medical products (TEMPS). The process of starting the standardisation for TEMPS was difficult, in part due to evolving products and intellectual property issues. Initial efforts therefore focused on nomenclature, test methods and guidances. Interest escalated rapidly and it was necessary to form a new division IV within the ASTM F04 and to include all participants.
The progression of ASTM to an international structure (ASTMI) and inclusion of the overall TEMPS-related professionals greatly enhanced the standardisation process. Soon all types of consensus standards were being developed, including issues of regenerative medicine in the broader context. As an officer member of ASTM and ASTMI, Committee F04's experiences with the evolving process of TEMPS standards were placed into perspective within the broader considerations of products for implant based reconstructive surgical procedures. From this perspective, of someone following the overall disciplines associated with surgical implants, the procedures using synthetic origin biomaterials for devices remained as the largest number.
Combinations of synthetic origin biomaterial devices and TEMPS (synthetic and natural origin) continue to increase rapidly and foretell of a time when TEMP-based devices will probably be used most extensively. However, it is not possible to fully predict the dynamics of new product introductions and acceptance as a standard of care, in part because of many factors that influence medical care on a worldwide basis.
Considerable progress has been made related to TEMPS and the multiple issues associated with regenerative medicine. This is strongly supported by the numerous consensus standards in the ASTMI F04 Division IV and now the coordination within the various non-US standards organisations, including the International Standards Organisation (ISO). The ISO Technical Committee 150 (ISO TC 150) new working group 7 is focusing on TEMPS documents and new items to be completed within harmonisation of world standards. These efforts and multiple inputs of new science and technology should be beneficial at all levels of society.
Considerations within the profession, especially within consensus standards organisations, often focus on the biocompatibility profiles of surgical implant devices. Initial tests for safety focus on construction and any byproducts associated with implantation and function.
In vitro tests for cytological safety utilise cell cultures, contact with blood and minimally invasive contact/implant procedures under controlled laboratory conditions. These tests have evolved over decades for testing existing and new synthetic origin biomaterials.
Testing sequences can normally be completed within a year for relatively reasonable expenditures. Protocols and standards for testing physical, mechanical, chemical and electrical properties of synthetic biomaterials are well established. These protocols and consensus standards have also been extended to the bioactive type biomaterials. Most existing bioactive substances interact with the host environment, but remain as an implant.
As the various disciplines move toward fully biodegradable natural and synthetic origin biomaterials, new tests are needed to assure acceptable biocompatibility profiles. In keeping with prior definitions, these profiles are specific to the intended application and stability of functional conditions within the host in vivo environment.
The questions for biodegradable devices are: what are the biological events leading to a fully regenerated tissue or organ and does this regenerated site replicate the original? From a testing viewpoint, how is this simulated and what information must be developed to assure safety and efficacy conditions?
Another change over the past few decades is the move to limit in vivo (animal) types of laboratory testing. Therefore, it is necessary to appropriately simulate the events associated with tissue and organ regeneration. Considerable additional science and technology is needed to fully evaluate the steps of biomaterial and/or device biodegradation and the associated biological response/interactions over time and function.
This situation is further complicated when considering nano-dimension biomaterial structures where ultra-high technical instrumentation capabilities are necessary. Considering the non-metallic biomaterials and devices, descriptions of properties have been provided at macro, micro and nano dimensions and bone has been defined in terms of properties at the nanometer scale. A desire to replicate bone properties at the nanocomposite scale has been one of the driving forces to consider nanofibre-reinforced polymeric composites vs metallics.
The rationale, in part, for biodegradable forms, especially combined with growth factors or biological cells, has been to enhance healing and to avoid known morbidities associated with non biodegradable devices. Although metallic implants for fracture fixation are often not removed after bone healing, most physicians continue to recommend that they should be surgically removed.
Considering the many important developments over the past decades, it is now suggested by many that nanofibre-reinforced polymeric composites should be reconsidered for applications of bone healing If the biomechanical properties of these structures were more similar to the bone, adverse sequellae associated with bone remodelling near metallic devices, might be minimised. If device design and biomaterial chemistry could be tailored to be given an initially strong and stable but also biodegradable condition over the longer term, this would be most desirable.
New and innovative ideas are evolving during the 2000s and many within the profession believe that biodegradable nano composites including active biologicals will find increased applications within the next decades. Many of these approaches are based on an ever-increasing need for enhanced healing of bone fractures, that healthcare circumstances of time and cost will not be prohibitive, and that funding for new R&D will be continued.