Fracture management in horses: Where have we been and where are we going?

ARTICLE IN PRESS The Veterinary Journal ■■ (2015) ■■–■■

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Personal View

Fracture management in horses: Where have we been and where are we going? Jörg A. Auer a,*, David W. Grainger b a b

Equine Department, University of Zürich, Winterthurerstrasse 260, Zürich CH8057, Switzerland Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112-5820, USA

A R T I C L E

I N F O

Article history: Accepted 1 June 2015 Keywords: Horses Fractures Internal fixation Fixation principles

Fifty years ago fracture management in horses was still in its infancy. The first attempts were undertaken to fix fractures with metal implants

such as screws and plates. The AO Foundation1 and its veterinary arm, AOVET,2 had the greatest influence on the progression of equine fracture management in the second half of the last century and the beginning of the present one. The acronym ‘AO’ stands for ‘Arbeitsgesellschaft für Osteosynthesefragen’, and the AO organisation, founded in 1958 by four visionary Swiss surgeons, is now globally recognised (Rüedi et al., 2007). AOVET was founded in 1968 and founding members quickly adapted fracture treatment techniques developed for human patients to animals such that many are applied today in daily practice with great success (Nunamaker, 2000; Houlton and Dunning, 2005; Auer, 2006; Rüedi et al., 2007). November 1968 witnessed the first documented internal fixations of a long bone in a horse under experimental conditions (Auer et al., 2013). After many preliminary trials with human plates applied to isolated cadaveric horse bones, human plates were applied for the first time to an osteotomised equine metacarpus III (McIII) in a live animal. A horse reprieved from a slaughterhouse was anaesthetised, and a transverse osteotomy performed on McIII using a special atraumatic, oscillating AO bone saw (Auer et al., 2013). At that time, Dr. Stephan Perren, Director of the AO Research Institute, Davos, Switzerland, was assessing the feasibility of using titanium plates for human fracture management and implantation of these plates in a horse was therefore a welcome test. The horse recovered rapidly and, after the bone had healed, all of the implants were removed (Figs. 1a–c). Metallurgic examination revealed neither damage nor wear and tear of the removed

Please note that the content in this Personal View article has not been subject to peer-review. The views expressed in this Personal View are entirely those of the author(s) and do not necessarily reflect those of the editorial team, or Elsevier. * Corresponding author. Tel.: +41 79 4143966. E-mail address: [email protected] (J.A. Auer).

1 See: https://www.aofoundation.org/Structure/the-ao-foundation/Pages/the -foundation.aspx (accessed 18 May 2015). 2 See: https://aovet.aofoundation.org/Structure/Pages/default.aspx (accessed 18 May 2015).

Introduction Revisiting and reviewing how major equine fractures were managed only a few decades ago compared to current state-of-theart treatments is an interesting and constructive exercise. Sadly (and unacceptably) too many horses that acquire simple fractures are still euthanased without trying to save them through surgical intervention. Of course, fracture treatment is expensive (especially if plates and many screws are involved) so conservative treatment using casts is still commonly an owner’s elective choice. However, employing an experienced veterinary surgeon to implant a few screws across a condylar fracture to get the horse out of the clinic within days and on to pasture within a few weeks may in fact prove to be more economical than keeping it in a cast, possibly with additional cast changes for many weeks. Selecting the surgical intervention option also considerably reduces the risk for foundering. This Personal View briefly looks at how internal fracture fixation in horses started, presents today’s successful techniques and takes a look at where fracture treatment in horses may go in the future.

Where have we been?

http://dx.doi.org/10.1016/j.tvjl.2015.06.002 1090-0233/© 2015 Elsevier Ltd. All rights reserved.

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a

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Fig. 1. One of the first clinical equine cases treated by B. von Salis with osteosynthesis according to the AO method. (a) Dorsopalmar (left) and lateromedial (right) radiographic views of a nondisplaced, biarticular, sagittal fracture of the proximal phalanx; (b) 14-week postoperative dorsopalmar radiograph of the healed fracture, which was treated with three inter-fragmentary cortex screws inserted in lag fashion.

implants. The horse spent its remaining life without any observable detrimental effects from the procedure. This successful initial osteosynthesis paved the way for the success story of internal fixation in horses over the following 50 years. The proper processes for treating equine fractures have taken decades to develop. First, techniques for first aid and transport of a fracture patient to the clinic had to be defined (Fürst, 2012). Then, improved fracture diagnosis, anaesthesia of the fracture patient (a very important factor in successful fracture management), the approach to the fractured bone, principles of internal fixation of long bones (see below), tissue closure, recovery from anaesthesia (including pool recovery), proper post-operative management and rehabilitation had to be established.

While most equine fractures are treated either by fragment removal using arthroscopic techniques (articular chip fractures) or by screw application using a lag technique (simple phalangeal, carpal, tarsal fractures, condylar fractures of McIII/MtIII, and selected avulsion fractures of long bones), only relatively few long bone fractures were initially treated by internal fixation using plates or other devices. The dynamic compression plate (DCP), developed by Allgöwer et al. (1973), was the first plate to facilitate progression of internal fixation in young horses. This became the mainstay for equine fracture treatment for many years (Fig. 2). However, studies in human medicine showed that the DCP caused demineralisation from plate stress shielding and remodelling osteoporosis under the plate

Fig. 2. Left: Craniocaudal and lateromedial immediate postoperative radiographic views of an open radius fracture treated by means of two staggered 4.5 mm DCPs. Right: Craniocaudal and lateromedial 8-month follow up radiographic views of the healed fracture following removal of the cranial plate.

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(Gautier et al., 1984; Perren et al., 1988). Although this has not been encountered in equine surgery, the issue led to the development of biologically improved plates, such as the limited contact dynamic compression plate (LC-DCP) (Gautier et al., 1984; Perren et al., 1988), and eventually to the locking compression plate (LCP), which remains the state-of-the-art implant for fixation of long bone fractures in humans, small animals and horses. To increase the stability of the fixation derived from friction between the implants and the host bone, a technique called plate luting was developed with the aim of achieving a 100% plate– bone contact by applying bone cement, polymethyl methacrylate (PMMA), between the plate and the bone (Nunamaker et al., 1986a). This was achieved after all of the plate screws had been inserted. The screws were loosened again, the plate lifted off the bone, the soft bone cement placed underneath it, and the screws re-tightened. The soft cement filled the oblong plate holes around the screw heads providing additional support, and making the fixation extremely rigid (Nunamaker et al., 1986a; Turner et al., 1990). When only the oblong plate holes were filled with bone cement, a similar (but smaller) increase in strain protection occured. Plate luting has been especially useful in repairing bones with anatomically complex surfaces that make contouring of the plate difficult (Turner et al., 1991). Plate luting in horses is however different from the plating practices used in humans and small animals where the developing vascular necrosis of the bone under the plate may result in pathological fractures after implant removal (Gautier et al., 1984; Perren et al., 1988). Where are we now? The principles applied presently in long bone fracture treatment in horses include the initial repair of the fracture by means of one or two 3.5 mm or 4.5 mm cortex screws inserted in lag fashion across the fracture at a location not occupied by the plates during surgery. The plate screws are inserted perpendicular relative to the surface of the bone. If a second plate is used, it is positioned such as to allow the screw holes of one plate to be located between the screw holes of the other plate (Bramlage, 1983; Sanders-Shamis and Bramlage, 1986; Auer and Watkins, 1987; Auer, 2012). This facilitates the insertion of all screws for both plates. One of the plates should be placed at the tension side of the bone, where the plates are the strongest. In DCPs and LC-DCPs, every hole in each plate should be filled with a screw (Bramlage, 1983). Should a hole traverse a fracture line, a lag technique should be applied by overdrilling the cis-cortex, and the screw should be directed so that it engages the opposite cortex distant from the fracture line. The plates should together span the entire bone. Staggering of the plates is acceptable and should be applied whenever it is not feasible to apply a plate from the distal to the proximal end of the metaphysis (Fig. 2), for example, for a plate applied to the lateral aspect of the radius spanning the entire bone (due to the craniocaudal bone curvature) the middle plate holes come to lie behind the bone, where no screws can be inserted. Where no support can be achieved in a cortex, bone cement may be placed and the screw implanted while the cement is still soft. After the cement hardens, the screw will be solidly fixed. Severely comminuted distal limb fractures are treated with selective screw insertion in conjunction with a transfixation cast (McClure et al., 1994a, 1994b, 1996, 2000), and has replaced the previously advocated external skeletal fixation device (Nunamaker et al., 1986b; Richardson et al., 1987). The LCP contains plate holes that combine two treatment methods in one implant, namely, compression plating and internal fixator techniques (Frigg, 2001; Marti et al., 2001). The LCP was developed to include the axial loading capabilities of the DCP and LC-DCP, the decreased plate–bone contact of the LC-DCP and the

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rigidity and stiffness of the less invasive stabilisation system (LISS), where angle-stable locking head screws were first introduced (Frigg, 2001; Marti et al., 2001). The goals were met by designing a ‘combihole’ where either a standard screw or a locking head screw can be inserted. It is not necessary to only apply locking head screws (Wagner and Frigg, 2006). An in vitro study comparing the application of two LCPs at right angles relative to each other with identical constructs using DCPs, LC-DCPs, and the clamp–rod internal fixators (CRIFs) in 4-point bending showed that implanting two locking head screws on either side of an oblique saw-cut across the artificial bone composite (Canevasit) provided significantly increased stiffness to the construct (Florin et al., 2005). Because the strength of a screw depends primarily on the core diameter and not thread width, the thicker core of the locking head screws and the thin threads make the screw several times stronger than conventional cortex screws (Tepic and Perren, 1995). By substituting cortex screws through some holes, costs can be significantly reduced without jeopardising the construct stability and stiffness. With no application of a ‘push–pull’ device or standard cortex screws, both of which press the plate onto the surface of the bone, a gap of 2 mm will be present between the plate and the bone after its application. Therefore a basic decision must be made at the start as to whether the plate must be in close contact with the bone or not. In horses, it is important to have solid contact between the bone and the plate to increase friction, which further stabilises the construct and helps to resist the extreme loading forces encountered in horses. Within a short period of time LCP has established itself as the preferred plate for equine fracture fixation despite its higher costs – mainly because of the screws (Levine and Richardson, 2007; Ahern et al., 2013). A recent study comparing 4.5 mm LCPs with 4.5 mm LC-DCPs confirmed the superior strength and stiffness of the LCP (Sod et al., 2008a, 2008b). The increasing popularity of locking plates has resulted in the manufacture of specially designed 5.5 mm LCPs for equine fracture repair. The plate was tested in an in vitro study against the 4.5 mm LCP (Sod et al., 2010) and the 5.5 mm LCP was found to be superior in resisting static overload in palmarodorsal 4-point bending and cyclic fatigue testing. The results were better than those achieved with the 5.5 mm LC-DCP and these findings established the 5.5 mm LCP as the ideal equine plate for specific long bone fracture fixation (specifically, the radius and tibia in adult Warmblood horses) and arthrodesis of the metacarpo/metatarso-phalangeal joints. The AOVET expert group, which develops new implants for veterinary applications, has recently implemented another change in plate design. While the human LCP has bevelled and pointed ends on both sides, the veterinary LCP has one bevelled and pointed end but the other side has a rounded end with a stacked combi-hole through which either a cortex- or a locking head screw can be inserted (Figs. 3a, b). The locking head part of the combi-hole is oriented towards the centre of the plate which allows the surgeon to position the rounded end at the end of a bone to insert a locking head screw and so avoid the bevelled end protruding over the joint. The LCP is presently the ideal plate for the veterinary surgeon (Fig. 4). It can be applied in the same manner as a DCP with only cortex screws. Because the plate possesses the same type of undercuts as the LC-DCP, it can be used in the same manner. In other words, the LCP fulfils all desired implant demands, and by purchasing only LCPs, the number of different plates that must be kept in stock ready for use can be considerably reduced. LCP pricing is only slightly higher than either the DCP or the LC-DCP and therefore costs are not a real problem. So, all that a veterinary surgeon must decide is whether to apply cortex screws, locking head screws, or a combination thereof. In selected fractures in young foals, the broad 3.5 mm LCP has advantages over the narrow 4.5 mm LCP (Fig. 5). The plate

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a

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Fig. 3. (a) A veterinary LCP (top) and a human LCP (bottom). The stacked combi hole can be seen at the left end of the veterinary LCP. (b) The stacked combi hole in a close up view.

Fig. 5. Craniocaudal and lateromedial immediate postoperative radiographic views of a transverse mid-shaft radius fracture in a 4-day old Warmblood filly, treated with a single 15-hole broad veterinary 3.5 mm LCP applied to the cranial, tension-side aspect of the bone. Note: the central hole was left open because it would have penetrated the fracture. By using this plate, seven locking head screws could be inserted into the distal- and six locking head screws together with a 3.5 mm cortex screw (most proximal screw) in the proximal main fragment. The plate spans the entire length of the metaphyses/diaphysis without penetrating the distal and proximal physes.

Fig. 4. Application of two LCPs to an oblique midshaft radius fracture. The fracture was reduced and repaired by means of three 3.5 mm cortex screws applied in lag technique. An 18-hole broad 5.5 mm veterinary LCP was applied to the cranial-, and a special 18-hole broad, human femoral LCP (slightly curved) was applied to the lateral aspect of the bone. Note: the slight side-to-side curve of the lateral plate allows the plate to span the entire length of the bone while facilitating screw insertion through all plate holes. Also, it would have been better to turn the cranial plate around and place the bevelled, pointed end of the cranial plate at the distal end of the radius. This would have resulted in a smoother transition from the distal end of the plate to the bone.

cross-section is the same but the combi-holes are smaller and closer together in the 3.5 mm LCP. Hence, more screws can be implanted in a broad 3.5 mm LCP than in the 4.5 mm LCP of the same length. The fact that the combi-holes are smaller makes the 3.5 mm LCP a stronger plate than the 4.5 mm LCP. Interlocking intramedullary nails have not established themselves in horses, primarily reflecting the lack of commercially available systems that can withstand the extreme forces exerted upon the implants when a horse is recovering from surgery and during the immediate postoperative period. The fact that relatively few fractures (simple, transverse fractures) can be adapted to allow successful use of these implants does not incentivise medical device companies to develop reasonably priced interlocking nails for horses. Another problem is the approach to the bone. The preferred extraarticular approach can relatively easily be achieved at the proximal end of the humerus and femur, but other long bones require a transarticular approach. Various experimental studies in vitro have shown mixed results compared with different plating techniques, underscoring the fact that interlocking intramedullary nails are (at best) equal to plates (Fröhlich, 1973; Watkins, 1990; Watkins and Ashman, 1991; McDuffee et al., 1994; Herthel, 1996; Herthel et al., 1996; Nixon and Watkins, 1996; Fitch et al., 2001; Lopez et al., 2001; Radcliffe et al., 2001; Galuppo et al., 2002). This may, however, change in the future. Presently, there is only one system in equine clinical use; it was developed at Texas A&M University, and has shown good results although it is not (yet) commercially available (Watkins, 2015). The best results achieved to date are in foals and younger horses, frequently in combination with unicortically applied LCPs (Watkins, 2015).

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Biological fracture fixation Recently, biological fracture fixation has become popular in both human and small animal osteosynthesis (Palmer, 1999; Pozzi et al., 2013). This technique abandons the dogma of anatomical reconstruction and accepts proper axial and rotational alignment of the bone (despite incomplete reconstruction) followed by fixation of the fracture with strategically placed implants. Longer plates are used in biological fixation, providing better leverage conditions. Screws are inserted through the biomechanically most important holes, but in this case, not all holes in the plate are filled with screws. The plates are pre-bent to conform to the shape of the contralateral intact bone. After distraction of the fractured bone to its original length and rotational correction of the dispalced bone fragments, the bone is approached through a small incision at one end and, after separating the soft tissues from the periosteum with a specially designed separator, the plate is slid along the fractured bone, and fixed with screws implanted through stab incisions. Such minimal fixation can rarely be applied successfully in horses. However, the principle of minimally invasive implant insertion is undoubtedly applicable and as relevant to the horse as to other species. The fact that locking head screws are angle-stable is also a valuable asset in fighting fixation breakdown: once screws are locked solidly in the plate, they do not align to the traction forces potentially applied to the construct as do cortex screws. One must also consider that it is possible to insert a locking head screw firmly into the plate even if the screw does not engage any bone; the screw feels solidly appied, leaving the surgeon with the false impression that the screw is placed into intact bone.

Fig. 6. High-definition musculoskeletal images taken of a human distal tibia with implants using a GE Revolution CT: 1 volume 120 kV/220 mA/0.5 s rotation. Left: a single axial 2-D reconstruction image. Right: a cranial view of the 3-D reconstruction showing the implants used to repair the human distal tibia and fibula fractures in red. Note: no stray radiation is visible. Photo courtesy of GE Corporation.

Surgery on the standing horse Increasingly, surgical procedures are performed with great success on the standing horse. This trend has also permeated orthopaedic surgery for techniques such as chip fracture removal, lag screw fixation of simple fractures and implant removal after a fracture has healed. This type of ‘local’ surgery, while to some extent increasing the risk of surgical site infection, avoids the need for general anesthesia and in doing so reduces costs. Surgical site infections Surgical site infections are still a significant problem in horses, and several steps must be implemented to reduce infection risks when treating long bone fractures in horses. These include: (1) wherever possible the periosteum must be left in contact with the underlying bone to ensure blood supply to the bone; (2) plates should be applied in areas where good muscle coverage is present; (3) effective pre-, peri-, and post-operative antibiotics must be provided; (4) at the end of surgery, antibiotic-impregnated polymethymethacrylate (PMMA) beads or strings of beads should be placed along the plates. Watkins (2015, personal communication) proposes to fill the unused portion of each combihole in the LCPs with PMMA loaded either with Tobramycin or Ciprofoxacin (2.5 g/200 g of PMMA). Care must be taken to avoid insertion of PMMA into the drive portion of the screw head because it prevents screw removal at a later date. (5) While closing the surgical wound, regional limb perfusion should be applied; (6) simple interrupted or vertical mattress sutures in the skin are the preferred closure technique, even though it takes longer than the placement of stainless steel staples. Diagnostic imaging Great advances have been made in different diagnostic imaging techniques. Already smaller movable computerised tomography (CT)

gantries are available for use in surgery rooms. Surgeons at the New Bolton Center, University of Pennsylvania, routinely use a CereTom mobile CT unit (NeuroLogica) before and during management of complicated fractures, and with great success (D. Richardson, personal communication). There is no doubt that in 10 years’ time this type of intraoperative imaging will be as popular as direct radiography is today. Newer technologies provide clear 3-D reconstruction CT images of vessels, soft tissue structures, and even bones containing metal implants (Fig. 6), overcoming many current problems, and even more refinements continue and evolve to improve intraoperative surgery management. Where are we going? Implants Despite the fact that locking implants have enabled great advances in equine fracture management, aspects of their use can still be improved and validated. In the future, all plates will have the variable angle LCP (VA-LCP) design, but presently these are only available in special human plates (Figs. 7a–c). Thinner and stronger plates, possibly combined with intramedullary transfixation nails, may improve the biomechanical deficits exhibited by current plates. Special plates for specific applications (e.g., T- or L-plates for proximal physeal fractures of the tibia) may represent a welcome improvement. Biodegradable plates and screws manufactured from either resorbable polymers (e.g., polylactides-co-glycolides and calcium phosphate composites with established clinical track records) (Eppley et al., 2004; Agarwal et al., 2009) or soluble metals (magnesium alloys; Chaya et al., 2015) can provide significantly increased fixation stability, strength and power. Commercialised currently for craniomaxillofacial use (e.g., DePuy-Synthes’ CMF Rapid Resorbable Fixation System) and tested in other orthopaedic fixation applications

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a

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Fig. 7. (a) The broad end the volar distal radial variable angle LCP (VA-LCP) demonstrating the angles available to insert screws through the holes; (b) birds-eye view of the plate hole design. The four ridges between the four holes contain threads, where the screw threads interdigitate with the plate; (c) close-up side-view of the screw head, depicting its threads on the rounded head and the star drive design for the screwdriver (Synthes).

(Rokkanen et al., 2000), these resorbable implants may become increasingly attractive in certain applications because they need not be removed. Foreign body responses are observed with highly and semicrystalline resorbable polymer devices (Böstman and Pihlajamäki, 2000) but non-crystalline resorbable polymers [e.g., 85:15 poly(Llactide-co-glycolide copolymer)] with improved tissue responses can lack the mechanical properties required for stable long bone fixation use. The disadvantage of intrinsically poor radiolucent polymer plate/screw visualisation in radiographs may be overcome by embedding or coating polymer implants with radio-dense materials, or perhaps by future innovations in implant diagnostic imaging that do not require electron density contrast with tissue. Combination devices are implants designed, approved and implemented clinically for a primary device (i.e., mechnical or structural) function, but containing an on-board secondary drug delivery or therapeutic property (Wu and Grainger, 2006). Nearly all orthopaedic combination devices in near-term clinical application are adaptations of existing orthopaedic (largely metallic) devices using drug delivering coatings. The DePuy-Synthes coated antimicrobial ‘Expert’ tibial nail is a prominent example. Newer orthopaedic implants are presently under development in both design and preclinical testing stages (Pioletti et al., 2008) that are actually designed to contain specific zones or areas where osteoinductive materials can be added to provide long-term effects for improved and facilitated bone healing (Neut et al., 2015). Intra-operative processing and customisation of implants with adhesive-applied matrices or printed drug-releasing coatings is also feasible as a possible future real-time customisation strategy for combination devices (Trajkovski et al., 2012). Fracture healing Fracture healing in horses is much slower than in humans and small animals (Schenk and Willenegger, 1963) and so measures to overcome this problem and facilitate healing are required. During the last decade, numerous research studies using bone morphogenic proteins (Lo et al., 2012; Mehta et al., 2012), and other growth factors (Nyberg et al., 2015), mesenchymal stem cells (Ma et al., 2014), and cell signalling molecules (Ito, 2011; Vo et al., 2012) have sought to accelerate bone healing (Amini et al., 2012); some have shown promise in various bone models and species, but convincing medical evidence for a consistent clinical bone regenerative strategy is still lacking (Kirker-Head, 1995; Jang et al., 2008; Fayaz et al., 2011; Kloss et al., 2013; Rolim Filho et al., 2013; Ferris et al., 2014).

More definitive support for precise dosing, timing, combinations of growth factors, cytokines, and/or stem cells, and implantable vehicles and methods of delivery will unquestionably contribute to improved healing designs and outcomes (Santo et al., 2013; Samorezov and Alsberg, 2015). While bone- and fat-derived stem cells can be relatively easily and inexpensively harvested and implanted either autologously or allogenically, standards for assessing their potency and healing potential for bone healing are presently lacking and clinical results in bone regeneration are unconvincing (Jones and Yang, 2011; Knight and Hankenson, 2013). The increasingly diverse advocacy and selection of bone-related growth factors for bone regeneration are confusing: they are frequently difficult to acquire in clinical grades and quantities, lack many delivery specifications for therapy, and are generally expensive. This situation is also likely to change in the future as demand increases and production methods mature, but presently remains a primary limitation to their clinical use. Multi-fragment fractures and complex implant management In the horse, severely comminuted long bone fractures are very difficult to manage successfully by means of internal and/or external fixation. Future developments will contribute new, non-toxic biodegradable bone rapid-set adhesives to assist in the anatomical reconstruction of the difficult fracture (Donkerwolcke et al., 1998; Farrar, 2012). One prerequisite of such bioadhesive compounds is their ability to reliably facilitate adherence of bone pieces to each other to form a stable union, but not to interfere with bone healing itself by programmed resorption. Bone adhesives currently in use do not yet have requisite mechanical properties sufficient to endure in vivo long bone applications. Synthetic adhesives (i.e., various polymeric adhesive combinations, magnesium phosphate cements, and polymer/ calcium phosphate blends) also commonly exhibit biocompatibility challenges that result in foreign body reactions, infections, and tissue necrosis. Testing systems and validation criteria that predict bone cement clinical success are currently equivocal producing confusion in how best to address current shortcomings (Farrar, 2012). The application of strategic metallic implants to the fractured bone in combination with novel bone adhesives that provide solid, mechanically robust bonds between fracture ends may produce a real advancement for treating difficult fracture cases. Identifying the smaller fragments in a multifragment fracture ahead of surgery using diagnostic imaging techniques and reconstructing them to a solid block of osteoconductive material using

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rapid-prototyping technology may turn out to be the first step in the successful management of severely comminuted long bone fractures. A second step might then involve intraoperative removal of the identified fragments, insertion of the pre-fabricated reconstructed bone-like implant block into the vacant space, followed by applying stabilising implants to form a solid construct. This may seem utopian today but the chances appear good that such approaches may one day become a reality in orthopaedic fracture repair. New, improved and more sophisticated implant designs for bone repair and regeneration can benefit further from computer-interfaced fabrication technologies. Current bone repair scaffold demands for improving bone regeneration opportunities are increasingly complex, considering many fabrication variables. Common design parameters for implants include matrix architecture, pore sizes, distributions and morphologies, surface properties for osseointegration and matrix degradation products, mechanical properties, and incorporation of diverse biological components (e.g., proteins, cells) with desired controlled variations of these factors within the implant volume and over duration of implantation. Additionally, the capability to produce patient-specific implants that fit specific defects or fracture sites, even seeded with the patient’s own sourced biological materials, is increasingly demanded (Hutmacher et al., 2004; Reichert et al., 2011). One currently popular method to duplicate bone and fracture defects utilises high resolution 3-D printing technology that exploits automated manufacturing throughput, computer-aided design and precision, informed by actual patient 3-D imaging data (Hutmacher et al., 2004; Bose et al., 2013; Ventola, 2014). This computer-aided and designed (CAD/CAM) fabrication strategy is also known as additive manufacturing, rapid prototyping, or solid freeform fabrication technology (Hutmacher et al., 2004; Gross et al., 2014), and for decades has been used for rapid prototyping in manufacturing well away from the biomedical field. This history has catalysed the rapid entrance and technology use in the ‘organ printing’ field, including musculoskeletal tissue. Medical imaging, computational modelling and implant scaffold fabrication are now readily achieved using rapid prototyping techniques (Hutmacher et al., 2004; Reichert et al., 2011; Ventola, 2014); CT scan images of patient-specific bone voids are used to generate a computer-based 3-D volumetric void model. The in silico model is then manipulated algorithmically using software and ‘sliced’ into thin horizontal layers from the total volume. These ‘sliced’ voidspecific data then instruct the 3-D printer to fabricate an implant scaffold, reconstructed layer by layer from the assembled volume slices, re-building the actual shape of the void from the computer model. Such printing technology based on CT images produces implant replicates from diverse biomaterials and variable complexities to address complex bone defects. Implants can be custommade to fit patient-specific voids, with scaffolds and cell constructs recapitulating complex musculoskeletal shapes, compositions and mechanics (Hutmacher et al., 2004; Reichert et al., 2011; Ventola, 2014). Bone 3-D printing implant generation is useful at several levels of practical orthopaedics. By exploiting CT scan data of a fracture, 3-D printers can rapidly print plastic bone-filling replicates within about 4 h, providing surgical teams with the precise bony component and opportunity to practice complex surgical reconstructions prior to actual patient surgery (Gross et al., 2014). The 3-D printed bone replicate approach is also currently used in orthopaedic surgeon training (Hoy, 2013), and specifically in veterinary surgical training (it was introduced in 2015 at Ohio State University, USA). Finally, actual biomaterial-based patient-specific solid 3-D printed implants comprising ceramic, metallic or polymeric biomaterials as liquid resins or powders are now common. Additionally, 3-D printed living cells, growth factors, other drugs, and complex material architectures can also be fabricated in complex mixtures, eventually

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also intra-operatively in real-time, at sub-millimetre precision for biologically active implants, allowing customisation, personalisation and direct implantation into patients (Murphy and Atala, 2014). Globally, both academic and commercial implant makers have promised human clinical trials for 3-D printed personalised bone-like biomaterials in 2015. Patient-specific 3-D printed bone implants now include the recent 510K regulatory approval from the US Food and Drug Administration (FDA) for a cranial bone void filler for repair of neurosurgical burr holes. Structural, mechanical and weightbearing bone implant applications require extensive validation in context. Overall, the rapid prototyping and 3-D computer-aided implant fabrication approach has a groundswell of popularity and the technical benefits of throughput, precision, duplication, capacity, cost, scaling and customisation. All of these exciting new developments will, at least in part, find their way into fracture treatment in horses. Computer assisted surgery Computer-assisted orthopaedic surgery has substantial potential to improve precision in the insertion of implants, but it is currently very expensive to acquire the necessary hardware and software (Andritzky et al., 2005; Rossol et al., 2008). Nevertheless, why should veterinary orthopaedic surgery not in time follow current human developments in this as in other fields? Who knows? Computer-aided surgery may one day become routine practice at least in specialised equine referral orthopaedic centres. Specialisation Because of the costs involved in fracture treatment, the need to store a large number of different implants at a clinic, the threats or risks of possible legal exposure for treatment liabilities, and demands by owners and trainers to restore their injured animals rapidly to functional use, it is likely that most long bone fractures in horses will in the future be managed in a few well-equipped orthopaedic centres that specialise in this type of surgery. Minor fractures, such as chip-, simple slab- and lateral condylar fractures will still be treated in regular racetrack- and surgery clinics. Also, emergency and rescue units will likely be established worldwide, at least where horse sporting and racing events are held, to provide first aid and state-of-the-art transport of the fracture patient to a specialised equine clinic. This type of transport was shown on live television a few years ago when Barbaro, the Kentucky Derby winner 2 weeks previously, had broken down at the start of the Preakness race. A helicopter followed the transport of the horse from Baltimore to New Bolton Center in Philadelphia. Equine services at the University of Zürich have also profited from such a service, producing evidence from results of equine fracture management in improved outcomes in patients transported by specialised ambulance services,3 with some horses arriving from as far away as northern Germany (Fig. 8). One key factor is the early recognition of impending complications, such as instability of the construct and infection. Immediate and appropriate clinical responses to the signs of such complications are required for best outcomes. Applying appropriate measures such as repeat surgery using stronger implants or meticulous lavage and curettage of the surgery site, respectively, and/or implantation of antibiotic-impregnated PMMA beads may solve the problem at an early stage, reducing costs of long-term treatment with expensive antibiotics and other therapies.

3

See: www.gtrd.ch (accessed 18 May 2015).

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Fig. 8. State-of-the-art emergency transport vehicle and trailer, equipped with a trolley for pulling recumbent animals into the trailer, video equipment that allow audiovisual communication between the driver and the technician in the trailer with the patient.

Management of patients

References

Equine clinicians must learn how to manage orthopaedic patients better post-operatively. Apart from welfare considerations that are often self-evident, pain management is a key element following surgery because it optimises patient comfort, prevents overloading of fixation constructs, especially in the early post-operative period, and often prevents complications. Numerous opportunities exist to improve treatment outcomes. Proper post-operative management and rehabilitation should start immediately following surgery and throughout the recovery period. More research and client education must be directed towards effective rehabilitation procedures to assure that the patient can return to its normal athletic activity. Unfortunately, equine-oriented orthopaedic research depends on a limited number of funding agencies, such as the Jockey Club, Grayson Foundation, Morris Animal Foundation, regional racing associations, and to some extent the AO Foundation, where competition for limited resources is fierce. New institutions and foundations supporting equine research are desperately needed to better support innovations, treatment validation through powered randomised studies, and clinician training in new techniques.

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Conclusions Fracture management in horses has made great progress in recent decades. The principles applied today are based on experiences made by the leaders in fracture management and consolidated during numerous AOVET training courses. Significant clinical problem areas such as severely comminuted long bone fractures in adult horses represent current treatment challenges. Present trends are towards standing procedures, minimally invasive techniques and the use of advanced real-time imaging techniques during surgical procedures. Because of the high costs and risks of using such devices, only specialised clinics operated by experts in the field of fracture management in horses will prevail. Clearly, not all fractures can be treated successfully so case selection is essential. We anticipate that future changes will occur in the adjunct fracture management sector, such as in new, improved combination devices and implants that provide bone stability and also contain designed features specific for loading and release of bone-healing and osteoconductive agents for local delivery, or to carry antimicrobial agents and implant features that mitigate infection.

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