Ординатура / Офтальмология / Английские материалы / Biomaterials and regenerative medicine in ophthalmology_Chirila_2010

18

Selected polymeric materials for orbital reconstruction

E. Wentrup-Byrne and K. George, Queensland

University of Technology, Australia

Abstract: Despite major advances in orbital reconstruction, the orbit is still considered one of the most difficult craniofacial regions to repair. This chapter gives an historical perspective of some of the most commonly used

materials including both non-biodegradable and biodegradable materials. The importance and nature of the material implant–tissue interface as well as the implant surface are discussed. Expanded polytetrafluoroethylene (ePTFE)

is the example used to illustrate the role of surface modification to improve currently used materials. Finally, a short overview of current and possible future directions in bone regeneration and tissue engineering is included.

Key words: orbital reconstruction, expanded polytetrafluoroethylene (ePTFE), surface modification, non-biodegradable polymers, poly(lactide-co- glycolide) polymers.

18.1Introduction

According to the literature and expert opinion, orbital reconstruction has advanced significantly over recent years. However, the general consensus still is that in the long term some of the most difficult craniofacial fractures and trauma damage requiring treatment are those related to the orbit. Restoration of facial defects is ‘a difficult challenge for both surgeon and prosthodontist’ (Beumer et al., 1996). In fact, a diverse team – involving various reconstructive surgeons, neurosurgeons, ophthalmologists, prosthodontists and, indirectly, the material chemists and engineers – is required in order to achieve the optimum outcome for the patient. Of the many challenges pertaining to orbital reconstruction, selection of the most suitable repair materials is but one. It is, however, ultimately the focus of this review. In order to discuss the wide range of materials available, it is necessary to understand and appreciate the complex structure of bone as well as the facial anatomy and treatment options. For those not familiar with the surgical and treatment demands in facial reconstruction, there are excellent books, such as Beumer et al.’s

Maxillofacial Rehabilitation, that cover relevant aspects. In Maxillofacial Trauma and Esthetic Facial Reconstruction, Cameron and Booth point out that because ‘the maxillofacial region is in many ways unique – the mindless transfer of orthopaedic techniques and principles is sometimes unhelpful’

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(Cameron and Booth, 2003). They recognise that the adoption of materials and fixation devices developed for orthopaedic use in the treatment of facial injuries is less than ideal, noting that it sometimes takes years for their proper evaluation in the craniofacial context to be realised. The breadth of conditions requiring surgical intervention with the use of repair materials can range from mild to serious trauma, post-traumatic deformities, defects resulting from tumour resectioning and genetic malformations. According to one recent review (Shuker, 2008) there has been ‘an unprecedented increase in blast eye/orbital injuries as a result of the increased use of explosive devices, land mines, rocket-propelled grenades, thermobaric enhancedblast explosives and explosive-forming projectiles’. A sad reflection on our society but also a confirmation that ‘plastic surgery’ is not just an aesthetic industry. In addition to the variety of traumas requiring intervention is the added complication of the additional issues involved when the patient is a growing child. Clearly, already several important issues have emerged that will govern the surgeon’s choice of material or materials: the nature and severity of the anatomic reconstruction to be undertaken and the permanency requirements of the repair. An additional issue that at first may appear a minor one but cannot be ignored is the question of patient acceptance. According to Beumer et al. (1996), ‘unrealistic patient expectations’ also need to be considered since the goal of any facial reconstruction is to ‘create an aesthetically pleasing and inconspicuous repair while preserving adequate function’. He ranks nasal prostheses/reconstruction at the highest satisfaction level with orbital and mid-facial prostheses/reconstruction at the lowest. Anatomic reconstruction is always demanding because of the complexity of the facial region but orbital trauma can involve not just damage to the fragile bones of the orbital rim but also damage to the bones of the floor within the orbital cavity, the eye itself, the eye lids and the lachrymal system, as well as other soft tissue damage.

The orbit comprises seven bones and all may require repair: frontal bone, maxillary bone, zygomatic bone, ethmoid bone, lacrimal bone, greater and lesser wings of the sphenoid bone and the palatine bone (Fig. 18.1). In addition, the bony orbit is divided into four compartments: superior, lateral, inferior and medial. The unique characteristics of each of these influence their response to trauma and hence each requires a strategic approach to their repair.

From a materials perspective, the reconstruction team have expectations of the commercially available materials with which they are required to work.

As is the case for most reconstructions – whether hips, arteries or facial – there is never one material that is ideal for all cases and situations. Since a comprehensive review of all aspects of an orbit reconstruction is beyond the scope of one chapter, we will attempt to give an overview of the choice of materials available for selected applications and a glimpse to the future as to what is expected of the next generation of repair and regeneration materials.

18.1Orbital bones, frontal view.

18.2Repair strategies

When discussing a repair ‘philosophy’ for a particular site, it becomes clear that every repair strategy must be tailored for that particular site, and recognising the different ‘environmental’ demands is essential. From a materials perspective, the chemical and mechanical characteristics of the materials being used in each unique environment need to fulfil the function for which they are intended. Broadly speaking, an example could be the different expectations of a material being used in a load-bearing vs a non-load-bearing site: the mandible vs the eye orbit. Materials used in a mandibular reconstruction will require very different mechanical properties to ones used in a nasal or orbit repair. In addition, some general factors that need to be considered are: the age of the patient, the nature – in particular, the size – of the trauma, the permanency of the materials used and whether osseointegration of the implant is desirable. As mentioned briefly in the introduction, the age of the patient is a critical factor in developing a repair strategy. Even in more straightforward craniofacial repairs, if bones are still growing, then clearly metallic or permanent non-biodegradable polymeric materials may be unsuitable and lead to revision surgery. In this review we will not address the particular needs of such patients, although a search of the literature reveals that a review on this subject might be overdue.

Another currently much discussed aspect of tissue repair and reconstruction, the newest approach, is that of tissue engineering or regeneration. In some craniofacial applications the use of tissue-engineered biodegradable polymeric scaffolds or constructs which, with time, stimulate the growth of, and are replaced by, the body’s own tissues has shown some success (Ueda, 2005). However, as far as can be ascertained, tissue regeneration

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is not currently an approach used in orbital repair. Since Chirila addresses this topic in Chapter 1 of this book, our emphasis in this chapter will be on repair and reconstruction. Quoting from the older but nonetheless (for the non-medical specialist) very informative Surgery of Facial Bone Fractures by Foster and Sherman, ‘ideally fronto-naso-orbital dislocations should be totally reconstructed in one initial, well-planned surgical enterprise’ (Foster and Sherman, 1987). Reading the literature, one becomes aware of the huge improvement in patient outcomes as a result of better trauma triage and surgical techniques but, although the research into improved materials is vibrant and on-going, there do not appear to be many new materials making it to commercialisation. In the words of Per-Ingvar Brånemark, one of the pioneers in the field of osseointegration of facial prostheses, ‘the use of alloplastic materials in or on the body is here to stay’ (Brånemark, 1997). Hence an overview of selected polymeric materials currently available and some discussion of the direction that future materials may take relative to the orbit reconstruction team may be timely.

18.3Nature of the trauma and its influence on material choice

Size appears to be one of the critical factors by which bone and orbit defects are usually categorised (Jelks and La Trenta, 1987; Ueda, 2005). Orbital fractures can involve one or more of the following: the orbital floor cavity, the rim and surrounding facial bones, and the soft tissues. For large fractures autologous bone remains the ‘gold standard’ and material of choice. In practice, the amount of bone harvesting required is the limiting factor. In medium to smaller defects, especially those where other facial injuries are limited, allograft bone may be the material of choice. However, while readily available, it is associated with some risk of disease transmission. The use of alloplastic (often polymeric) materials reduces disadvantages such as cost, donor-site morbidity and increased operation time, but their use has been associated with a higher potential for infection (Firtell and Beumer, 1979). This is a significant problem in light of the fact that, of the many facial sites where restorations are routinely carried out, orbital reconstructions are the most prone to infections. In addition, in many cases more than one repair material is required. For example, when using autogenous or allograft bone, a polymer-based bone cement such as poly(methyl methacrylate) (PMMA) may also be needed.

In many orbital reconstructions the issue of orbital volume is a critical factor. After enucleation, it is essential to maintain orbital volume before an orbital implant is fitted (see Chapter 17). Again, a combination of materials may be needed in order to repair the orbital rim and floor in preparation for the actual implant (Jelks and La Trenta, 1987). Where maxilloand

craniofacial repair and reconstruction are concerned, it was generally accepted some time ago that, in the case of fixation devices, ’small is good’ (Cameron and Booth, 2003). Hence, the current debate has moved on from the size of the fixation device – microand mini-plates are now the ‘gold standard’– to whether resorbable or non-resorbable plates and screws are best. In the course of preparing this review, the fact that literature references came to light calling Teflon® an ‘inorganic material’ (which it is not) and Medpor® a fluoropolymer (it is not), although Teflon® is, highlights the difficulties facing writers who, although experts in their own fields, face an alarming range of terms and definitions from other specialities. In the following sections we will endeavour to present an overview of some issues relevant in orbital repair strategies with a focus on selected polymeric materials.

18.4Choice of materials for repair

One of the earliest recorded materials used in craniofacial repair and restoration is gold, although it must be admitted that the history of facial repair and reconstruction has not been well documented. There are some discussions in the literature and even more information on the web that fascinating reading even if their historical accuracy is sometimes somewhat doubtful (Beumer et al., 1996; Firtell and Beumer, 1979). One of the most interesting is the story of Tycho Brahe’s artificial nose (1566) (Van Helden, 2005). After losing his nose (or part of it depending on which account one reads) in a duel he had a gold/silver prosthesis fitted using an ‘adhesive balm’ to keep it in place. Although renowned for his astronomical discoveries, this incident apparently kindled his keen lifelong interest in medicine. Since then many different classes of materials have been studied and trialled clinically for craniofacial repair and/or regeneration: bone autografts and allografts, ceramics (Bioglass®), metals (tantalum and titanium alloys), alloplastics and, more recently, metal/ polymer composites. According to an earlier review, ‘little information is available comparing the benefits, complications or selection criteria of the 20 or so alloplastic materials available for the repair of orbital blow-out fractures’ (Fries, 1994). Meyer’s excellent review, ‘Alloplastic materials for orbital surgery’ has a relevant section on bony orbital reconstruction

(Meyer, 1995). A search of the literature, however, failed to produce more recent reviews or new critical evaluations. This may reflect both clinical and research interest in ‘new’ materials when they first become commercially available, as well as the need to evaluate their performance in both animal models and in clinical studies. Once their clinical efficacy, their advantages and disadvantages have been established, interest dies. In addition to this more general overview of the materials available, a selection of materials will be discussed in more depth in the following sections. Currently, microand mini-plates and meshes are commonly used both in orbital floor and rim

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repairs. These can be either permanent (titanium) (Mackenzie et al., 1999; Oliver, 2000) or made from bioresorbable polymers such as polyglycolide and lactide (e.g. polyglactin 910) (see Section 18.6). Patents are currently pending for a recently developed composite material found in a series of Medpor Titan® products, which consist of a titanium mesh covered with a thin coating of high density polyethylene (HDPE). The advantage of using such composite materials is that they combine some of the advantages of both materials (in this case both materials are routinely used in a range of applications): a polymer with a metal that has good osseointegrative properties (Eppley, 2003b). They are mostly used in orbital floor and wall fracture repair. Which permanent materials are used and whether or not they should be left in place once their function has ceased are much-debated topics. For example, fixation devices (plates and screws) are often needed in conjunction with polymeric materials in order to assist healing. Cameron and Booth discuss how in Germany, for example, metal fixation devices are often removed, whereas in the UK and USA their removal is less common

(Cameron and Booth, 2003). Although the use of bioreosorbable plates and screws is well established in orthopaedics, their use in craniofacial surgery is more limited but is increasingly being considered (see Section 18.6).

According to Eppley (and others too of course) (Eppley, 2003b), the concept of an alloplastic material is synonymous with the term ‘synthetic’ and coming from a non-biological source. The term ‘alloplastic’ when used in the medical literature covers manufactured materials from ‘non-organic, nonhuman, non-animal sources’, and encompasses ceramics and metals as well as plastics (which to chemists and engineers means polymers). Broadly speaking, polymeric biomaterials are divided into either permanent, non-biodegradable such as PE or polytetrafluoroethylene (PTFE), and bioresorbable polymers such as the poly(lactic acid)-based LactoSorb® (Biomet, Microfixation, FL, USA). Some of the criteria that need to be considered in choosing a repair material are summarised as follows: cost-effectiveness, biocompatibility, toxicity, antigenicity, carcinogenicity, inertness, capability to protect and provide the support that would normally be given by the defective bone; in addition, in many cases the material must be easily shaped at the operating table. It has been pointed out that ‘surgeons are vulnerable to market forces from the manufacturers of fixation devices’ and that ‘we must always look critically at new devices since new ideas and philosophies develop’ (Eppley, 2003b). Ultimately, however, it is the surgeon who must make the critical decision regarding the choice of material and it is this informed choice that will have an impact on the clinical outcomes for the patient. To summarise: while the anatomical demands of the orbital site and superb surgical expertise are major contributing factors to a positive clinical outcome, undoubtedly the judicious choice of a biocompatible and successful functioning implant material is also essential. Table 18.1 summarises the polymeric materials most commonly used in orbit repair.

18.5 Non-biodegradable polymers

18.5.1 Polytetrafluoroethylene: introduction

PTFE (Fig. 18.2) is one of a family of fluoropolymers that have been used in medical materials and devices for many years. A perusal of the literature highlights the wide range of applications using expanded PTFE (ePTFE) and its story is a good one to illustrate the long journey of a material from laboratory to industrial applications and finally its adoption in the biomedical arena (Chandler-Temple et al., 2008).

Table 18.1 Polymers used in orbital reconstruction

HDPE, high density polyethylene; UHDPE, ultra high density polyethylene; PHDPE, porous HDPE.

*Polymers discussed in this chapter.

could present an exciting commercial opportunity for another manufacturer to enter this important market.

18.5.2 Applications

ePTFE has proven most successful in maxillofacial and periodontical applications, where it has been used as a barrier membrane for guided bone regeneration (GBR). In 1987, Karesh published the first paper specifically evaluating PTFE for ‘ophthalmic plastic and reconstructive surgery’ (Karesh, 1987). The paper reported both a rabbit model and a clinical study, and overall the conclusions were most positive. In a more recent review on the use of membranes for bone healing and neogenesis, Linde et al. state that ‘virtually all investigations published on the promotion of GBR using membranes have utilised ePTFE membranes’ (Linde et al., 1993). Other cranial and facial applications that have benefited by the use of ePTFE membranes and ePTFE membranes reinforced with fluorinated ethylene–propylene (FEP) are at the bone interface repair sites where limited mechanical loading exists. A literature search reveals that many papers reporting their use involve the orbital floor or orbital blow-out fracture repairs (Elmazar et al., 2003; Fries, 1994; Linde et al., 1993; Meyer, 1995). In 1994, Hanson et al. evaluated the efficacy of ePTFE sheets for orbital floor reconstruction in a domestic sheep model (Hanson et al., 1994). Later that year, Karesh, who had already pioneered ePTFE use in ophthalmic applications, published (in the words of Meyer) ‘an erudite discussion’ comparing ePTFE and HDPE for orbital repair (Karesh, 1994); Karesh analysed Hanson’s study (Hanson et al., 1994) and concluded that further studies were needed in order to evaluate the merits of ePTFE and HDFE, especially in the case of larger orbital defects (Karesh, 1994). In recent years many of the specialist surgeons working on the head and face have been widening their areas of operating interests. This leads to some overlapping of specialisations, as well as some confusion for the general public in knowing which specialist surgeon is best consulted for a particular reconstruction. This impression is confirmed by at least one expert in the field (Karesh, 1998). He points out that it would be necessary to ‘consult journals in maxillofacial surgery, ear, nose and throat surgery, plastic surgery, ophthalmology and oculoplastic surgery to get a complete overview of all the procedures and techniques involved’. The fact that, in the hands of all these specialist surgeons, ePTFE has proven useful as a repair material at the soft–hard tissue interface merits further discussion.

18.5.3 The implant–tissue interface

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the different tissues and the material–tissue interfaces. From both a chemical and biological perspective every interface presents a challenge in view of the fact that every ‘treatment choice’ will ultimately influence the final clinical and patient outcomes. The bones that make up the facial area surrounding the orbit are continuous with the orbit cavity and its walls, and they all form interfaces with the surrounding soft tissues (e.g. the eye lids) and systems such the lacrimal system. Added to Karesh’s observation of the difficulty of covering the entire literature is the fact that complicated reconstructions involve more than one facial feature and hence a range of materials. In his various papers, he describes how ‘PTFE implants, HDPE, polyester and polyglactin sutures, hydroxyapatite, absorbable screws and plates as well as cyanoacrylate glue’ may all be required. Elmazar et al. are among those who point out that fixation of the PTFE implant to the orbital rim often requires a fixation device such as titanium screws or a micro-plate (Elmazar et al., 2003). This creates a metallic–polymer interface which in turn means new synergies between all the different materials: biological and alloplastic.

18.5.4Surface modification of expanded polytetrafluoroethylene

Ikada has described how the surface modification of polymeric biomaterials is a well-established method of improving commercially available products (Ikada, 1994). Over the years, much fundamental research has gone into improving the performance of various PTFE products for vascular and craniofacial applications (Colwell et al., 2003; Nishibe et al., 2001).

PTFE is a fully fluorinated unbranched polymer with a carbon backbone (Fig. 18.2) that contains fluorine atoms bonded to carbon to form C–F bonds. It has a helical conformation (Fig. 18.2(b)). These are the strongest chemical bonds found in polymers: this means that PTFE is extremely stable and hydrophobic. These chemical properties translate into non-adherent material surfaces with significant anti-frictional properties (excellent in vascular devices) (Kannan et al., 2005). However, proteins and cells find such surfaces very unattractive. Since they play an important role in hydroxyapatite nucleation and bone growth this becomes an issue (Kasemo and Gold, 1999; Wilson Cameron et al., 2005). A material surface to which proteins and cells attach is described as ‘bioactive’. The bone/soft tissue–material interface requires at least some degree of attachment; yet, a fibrous tissue interface is undesirable as it can lead to micromotion and destabilisation of the implant (Maas et al., 1993). Hence, a porous material with the propensity to vascularise and form a good interface with the surrounding bone and soft tissue is highly desirable from both the surgeon’s and the patient’s perspective. As will be discussed below, researchers have examined the custom-modification of