P-5 Paradigms and Progress in Trauma and Orthopaedics

Plenary Lectures / Journal of Biomechanics 43S1 (2010) S3–S14

and macrophages are recruited within the first 24 hours after tendon injury to clean up necrotic materials and cells, and release some growth factors for the initiation of the second phase, proliferation, which starts a few days after the inflammatory phase, and lasts up to six weeks. This is the most crucial phase in connective tissue healing. The size of the local cell population is an important factor influencing the amount of proliferation in the second healing phase. However, the flexor tendon is hypovascular and hypocellular, resulting in a long-term healing process compared to other tissue healing. The most common complications following tendon repair occur during this phase. Strategies to improve tendon healing, therefore, mostly focus on in this phase, including cell-based therapy, growth factors stimulation, platelet rich plasma (PRP) augmentation, and some physical modalities. The last phase of healing, remodeling, is critical for functional tissue regeneration. During this phase, cytokines, such as MMPs, and mechanical stimulation are the most influential parameters. For flexor tendon remodeling, mechanical strength should allow muscle force transmission and also a smooth surface must be restored to enable functional performance. Intrinsic healing indicates that tissues can be directly healed by proliferation of residual cells within injured tissues, which results in superior outcomes. Intrinsic healing of flexor tendons mainly relies on the migration of epitenon cells from the tendon surface into the lacerated tendon ends since the endotenon cells have less capability to proliferate and differentiate. In contrast, extrinsic healing relies on the invasion of cells from the surrounding tissues to bridge tendons together, which leads to adhesion formation between tendon and surrounding tissues, hindering tendon gliding. However, extrinsic healing is faster and more abundant compared to intrinsic healing due to a rich blood supply and high cellularity in the surrounding soft tissues. Elimination or reduction of extrinsic healing has been investigated with the strategies of physicochemical and pharmacological interventions, but at some cost in terms of delayed or impaired tendon intrinsic healing as shown in our recent studies. Postoperative rehabilitation is also an effective therapy to decrease the adhesions formed by extrinsic healing. However, inappropriate motion therapy can also cause gap formation, and even repaired tendon rupture. Maximization of intrinsic healing and minimization of extrinsic healing still remains a great clinical and research challenge. Finally, tendon healing has two patterns of healing, i.e. contact healing and gap healing. Contact healing indicates that lacerated tendon ends directly contact each other; the tendon heals by first intention and is dominated by intrinsic healing. Most connective tissues heal by this phenomenon, such as bone, skin, and other less tensile tissues. However, the tendon, especially flexor tendon healing, primarily follows gap healing, which is similar to wound healing in the secondary intention. The function of tendon is to transmit muscle force to the bone to move joints. Tensile force always exists during joint motion, especially during postoperative rehabilitation, which is often performed to prevent adhesion formation in the early stage following tendon repair. Although lacerated tendon ends can be brought together by surgical repairs, the tensile force often causes the gap formation at the repair site. This gap healing not only elongates the healing phases, but also involves more extrinsic healing. The strategies to eliminate gap healing have been studied for many decades, including strong repair techniques, suture materials, and postoperative rehabilitation protocols, but tendon gap healing still remains an unavoidable problem. In summary, flexor tendon healing, like other connective tissues, has two physical forms (contact and gap healing) and two healing resources (intrinsic and extrinsic healing) through three healing phases (inflammation, proliferation, and remodeling). The fundamental strategies to improve the outcomes of flexor tendon injury and repair should focus primarily on achieving contact healing, secondarily on eliminating extrinsic healing, and then

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finally shortening the healing phases. This principle is also applicable to healing of other connective tissues. P-4 Biocompatibility and Bioactivity of Bearing Loaded Metallic Implants A. Zielinski, S. Sobieszczyk, B. Swieczko-Zurek, A. Ossowska, T. Seramak, W. Serbinski. Gdansk University of Technology, Poland The aim of the presented project is to develop the Titanium (Ti) alloy base composite materials possessing better biocompatibility, longer lifetime and bioactivity behavior for bearing loaded implants, e.g. hip joint and knee joint endoprosthesis. The development of such material will be performed through modeling the material behavior in biological environment in long time and develop new procedures for such evaluation; obtain the extremely biocompatible Ti alloy with design porosity; develop the oxidation technology resulting in high corrosion resistance and bioactivity; develop the technologies of deposition of Hydroxyapatite (HA) based composite bioactive coatings; develop the technologies of obtaining the bioactive composite core materials placed within the pores. The examinations of degradation of Ti implants are carried out in order to recognize the sources of both short allergies and inflammation, and long term degradation. The theoretical assessment of corrosion is made assuming as caused by three processes: Electrochemical dissolution through imperfections of anodic oxide layer, diffusion the metallic ions through oxides, and dissolution of oxides themselves. In order to increase the biocompatibility the toxic elements, Aluminum (Al) and Vanadium (V) are eliminated. The experiments have shown that titanium–zirconium–niobium (Ti-Zr-Nb) alloy may be such a material that can also be prepared by powder metallurgy (P/M) technique. The porous (scaffold) Ti-Zr-Nb alloy is obtained by powder metallurgy, classical and with spacing holders used before melting and decomposed, or used during melting and removed by subsequent water dissolution. The oxidation of porous materials will be performed by electrochemical technique in special electrolytes in order to obtain the oxide layers well adjacent to an interface, preventing the base metal against corrosion and bioactive because of nanotubular structure, permitting injection of antibiotics into the pores. The Calcium (Ca), Oxygen (O) and Nitrogen (N) ion implantation or deposition of Zirconia sublayers will be explored to increase the biocompatibility and bioactivity. The HA coating obtained by electrophoretic deposition will result in gradient structure similar to bone structure, and biomimetic HA deposition will have an effect of bioactivity. The core material of the porous material likely composed of HA and organic polymer and other compounds will result in slowly degraded bioactive material, allowing slower dissolution followed by stepwise growth of bone tissue and angiogenesis, preventing the local inflammation processes, sustaining the mechanical strength close to that of non-porous material. P-5 Paradigms and Progress in Trauma and Orthopaedics M. Kimmons. CEO British Orthopaedic Association, UK The prevailing worldview in any organisation or culture determines not only the kinds of questions we ask but also the answers we expect. When an individual crosses from one culture to another it provides a unique, and sometimes traumatic, opportunity to both challenge and enrich the new from the perspectives of the old. The military world has clarity of purpose which is vital to not only the success of its mission but also the safety of its stakeholders. In this session a former Royal Navy Rear Admiral with 35 years of experience in the complexities of military organisation, reflects on both the benefits of his previous experience and the values that underpin his new situation. The British Orthopaedic Association (BOA) brings together a unique clinical community with academic and industrial partners in an

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Plenary Lectures / Journal of Biomechanics 43S1 (2010) S3–S14

enterprise of excellence in practice, research and education. In this world ensuring clarity of vision on a daily basis similarly safeguards stakeholder safety in the form of patient care. In so doing the BOA must also achieve synergy between a variety of potentially conflicting interests. The challenges facing the BOA and the community it represents are as complex and absorbing as any faced in a military campaign. This plenary will review those challenges and seek to provide a fresh perspective on how they may be faced. P-6 Stem Cells in Low Back Pain Y. Lok, S. Hughes. Imperial College London, UK Chronic low back pain is a common condition affecting 10% of the population [1] and is associated with degeneration of the intervertebral disc (IVD) [2]; which occurs as a result of inflammation in the disc and death of the nucleolus polposus (NP) cells. The NP cells are vital in maintaining the biomechanical strength of the disc. Inflammation and necrosis of these cells triggers a vicious cycle of inflammation, metalloproteinase secretion, degradation of extracellular matrix within the NP, leading to further cell death, desiccation (and/or herniation) and loss of disc height. The local release of inflammatory cytokines is also thought to sensitise local nerve roots causing radiculopathy and effecting degenerative changes to the local vertebral structures [3]. The logical cure for disc degeneration therefore would be to restore the NP cells, and allow them to regenerate the extracellular matrix. Unfortunately, NP cells have very low metabolic activity and poor regenerative capacity in their natural environment. It is possible however, to expand the number of NP cells through in-vitro culture. Culture expanded cells harvested from surgically removed IVDs injected into animal disease models showed increased proteoglycans content and restoration of disc height [4]. In the Euro Disc trial [5], 112 patients were recruited for autologous disc cell transplantation (ADCT), in which patients requiring surgery for disc herniation had their affected disc removed, cultured and replanted 12 weeks after. The interim report at 2 years (2006) on 28 patients demonstrated better functional outcome and less disc height loss in the treatment group compared to the control. Despite the apparent efficacy of ADCT, there are limitations. The paucity of NP cells means not all harvested IVDs can yield sufficient cultured cells. The harvesting process requires sacrifice of an IVD; restricting the technique to patients undergoing surgery. Mesenchymal stem cells (MSCs) can differentiate into progeny with NP cell-like characteristics in culture [6]. Animal models utilising MSCs have showed promise as well. The ready availability of MSCs, with no IVD sacrifice, means cellular therapy can also be applied to patients where surgery is not. The immune-privileged NP niche also opens the possibility of using allogenic stem cells. However, the human degenerative disc is a chronic, inflammatory condition in a load bearing structure, while most experiments were performed on 4-legged mammals with an acute disc injury. Cadaveric studies by Roberts et al [7] showed that a higher proportion of NP cells in herniated discs were in senescence compared to those in non-herniated discs; possibly because of the pro-inflammatory, high oxidative stress of the niche environment. This raises doubts on whether cellular therapy can successfully repopulate the NP and regenerate the extracellular matrix in humans. Nevertheless, the anti-inflammatory properties of MSCs may be able to mitigate these effects. The trigger for inflammation and cell death in the NP is unknown, but is thought to be associated with disruption to disc nutrition [8]. The NP cells are nourished by passive diffusion of solutes delivered by the end-plate vasculature [9]. Diseased discs have been found to have delayed gadolinium transit times in MRI studies [10]. Cadaveric studies by Boos et al [11] found an association in the reduction of end-plate blood supply and increased NP degeneration. End-plate

vasculature therefore plays a key role in the long-term health of the disc. In 2003, Luk et al [12] reported the technical feasibility of transplanting cadaveric discs with their associated end-plates into live patients. Although the transplanted discs showed accelerated degeneration within a few years, it does offer a possible avenue of overcoming end-plate vascular degeneration; end-plate replacement. This paper will present the authors views on the possibility of using stem cells in clinical practise in order to treat patients with low back pain. Reference(s) [1] Andersson GB. Epidemiological features of chronic low-back pain. Lancet 1999;354(9178):581–5. [2] Luoma K, Riihimaki H, Luukkonen R, Raininko R, Viikari-Juntura E, Lamminen A. Low back pain in relation to lumbar disc degeneration. Spine (Phila Pa 1976) 2000;25–4:487–92. [3] Brown MF, Hukkanen MV, McCarthy ID, Redfern DR, Batten JJ, Crock HV, Hughes SP, Polak JM. Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease. J Bone Joint Surg Br 1997;79–1:147–53. [4] Ganey T, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ, Hutton WC. Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine (Phila Pa 1976) 2003;28–23:2609–20. [5] Hohaus C, Ganey TM, Minkus Y, Meisel HJ. Cell transplantation in lumbar spine disc degeneration disease. Eur Spine J 2008;17 Suppl 4:492–503. [6] Anderson DG, Risbud MV, Shapiro IM, Vaccaro AR, Albert TJ. Cell-based therapy for disc repair. Spine J 2005;5–6 Suppl:297S-303S. [7] Roberts S, Evans EH, Kletsas D, Jaffray DC, Eisenstein SM. Senescence in human intervertebral discs. Eur Spine J 2006;15 Suppl 3: S312–6. [8] Wallace AL, Wyatt BC, McCarthy ID, Hughes SP. Humoral regulation of blood flow in the vertebral endplate. Spine (Phila Pa 1976) 1994;19–12:1324–8. [9] Crock HV, Goldwasser M. Anatomic studies of the circulation in the region of the vertebral end-plate in adult Greyhound dogs. Spine (Phila Pa 1976) 1984;9–7:702–6. [10] Niinimaki JL, Parviainen O, Ruohonen J, Ojala RO, Kurunlahti M, Karppinen J, Tervonen O, Nieminen MT. In vivo quantification of delayed gadolinium enhancement in the nucleus pulposus of human intervertebral disc. J Magn Reson Imaging 2006;24–4:796–800. [11] Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG. Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine (Phila Pa 1976) 2002;27–23:2631–44. [12] Ruan D, He Q, Ding Y, Hou L, Li J, Luk KD. Intervertebral disc transplantation in the treatment of degenerative spine disease: a preliminary study. Lancet 2007; 369–9566:993–9.

P-7 Future Directions in Knee Replacement P.S. Walker, G. Yildirim, S. Arno, Y. Heller. NYU Hospital for Joint Diseases, New York, NY, USA The use of artificial joints for the treatment of osteoarthritis is expected to expand considerably over the next decade. While newer technologies can offer yet further improvements in total knee systems, implementation will be strongly affected by the need to satisfy apparently competing requirements. Patients expect quicker rehabilitation, improved performance, and lifelong durability; on the other hand, economic constraints require a reduction in cost for each procedure, as well as early intervention and preventative measures, while there is increased pressure from health care systems to use evidence-based medicine as the standard of choice for implants and techniques. The success of a knee replacement depends upon the design itself, the surgical technique, the rehabilitation, and, not least, the patient. The major goal of the implant design can be redefined as a restoration of normal knee mechanics, whether by maximum preservation of tissues, or by