boekwerk orthopedie def - BioTec Maastricht2 assessment of failed implants to learn how to improve implant design and ﬁ xation techniques 3 improvement of conservative (i.e. non-surgical)

o r t h o p a e d i ek e e p o n m o v i n g

Department of Orthopaedic Surgery Maastricht

Educational Centre

Medical School

Orthopaedic Trainees

Centre of Excellence

Regional Hospital

University Hospital

Osteoarthritis Clinic

Spine Clinic

Paediatric Orthopaedics

Sports Medicine & Traumatolgy

Research Department

Research LabOrthopaedics

GROWBasic research

Trial BureauOrthopaedics

CAPHRIClinical research

Medical Field Lab

The Department of Orthopedic Surgery has three main tasks: education, patient care and research. The education

programme involves participating in Maastricht University’s Faculty of Health, Medicine and Life Sciences and training MDs to become orthopaedic surgeons. Our Centre of Excellence provides fellowships and short training visits for orthopaedic surgeons from all over the world.

The clinic provides both regional and top referral patient care. In addition, the MUMC+ (Maastricht University Medical Centre) is the only university medical centre in the Netherlands that serves both functions in a single centre. This provides our department with additional opportunities and when researching chronic diseases such as osteoarthritis, the possibility to treat and monitor patients from an early stage.

We engage in four main areas of clinical interest: Osteoarthritis, Spine, Paediatric Orthopaedics and Sports Medicine and Traumatology. In accordance with these focus areas and top referral patient care, our research primarily concentrates on two research lines: Osteoarthritis and Spine. An osteoarthritis clinic (Artrose Kliniek Maastricht) and spine clinic (Spine Centrum Maastricht) were recently established to integrate patient care with fundamental and clinical research.

We have a strong vision on how clinical related research should be organised. Clinical issues are translated into research questions and in the laboratory we attempt to fi nd answers and solutions that we can subsequently implement in clinical practice. We are thus constantly working to create a continuum between clinic and laboratory. In this way we are building a new organisation that is able to compete at both a national and international level.

On behalf of the Department of Orthopaedic Surgery.

Prof. dr. L.W. van Rhijn

Prof. dr. G.H.I.M. Walenkamp

Osteoarthritis Clinic Maastricht (Artrose Kliniek Maastricht, AKM)In the near future, osteoarthritis-related joint complaints and their treatment

will increase exponentially. The babyboomers generation has reached an age at which osteoarthritis (OA) is liable to occur. However, this age group is still very vital and keen to maintain a dynamic daily lifestyle for as long as possible. Current OA treatment consists in conservative or surgical treatment (depending on the severity of the disease) with a total joint prosthesis as a last option. These joint prostheses, however, have limited lifespans. For patients with mild or moderate OA, several conservative treatment options (life rules, limiting load or ortheses) are possible. In the Osteoarthritis Clinic Maastricht, patients with early-stage arthritis receive information about OA and can discuss the treatment possibilities for conservative pain relief. Those who have developed severe OA, requiring operative treatment, are coached in the rapid recovery programme Healthy Healing (‘gezond genezen’). Further information about the AKM is available at www.artrosekliniek.nl.

Spine Clinic (Spine Centrum Maastricht)

Back and neck pain are among the main causes of physical disability and pain in modern society. The annual costs of work absenteeism and early retirement

due to back pain are huge. Back pain and subsequent disability can be caused by degeneration of the spine but are also infl uenced by psychosocial factors and work status. Therefore, it is important that back pain is evaluated in all its aspects, which entails a multidimensional and multidisciplinary approach. The Department of Orthopaedic Surgery has taken the lead in this regard by developing a spine clinic where patients can be evaluated and treated in a cross-disciplinary manner that further enhances the quality of spinal care.

Department of Orthopaedic Surgery research laboratoryOur research laboratory facilitates applied and fundamental research on the

various orthopaedic topics mentioned above. It investigates the development and regeneration of cartilage and bone, as well as the (molecular) mechanisms that infl uence this process. Importantly, we focus on methods and knowledge that, ultimately, are also applicable for clinical use in cartilage and bone regenerative medicine. A second focal point is orthopaedic biomaterials and the development of innovative solutions for prosthesis and surgical technologies.

In our research, we cooperate with several national and international partners and participate in various collaborative projects. To ensure the translational character of the research, we link fundamental science from the lab with the clinic via the Department of Orthopaedic Surgery’s Trial Bureau.

Trial Bureau: Clinical evaluation of new implant technology Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are considered

highly successful interventions for total joint arthritis. The major surgical challenges in current orthopaedics are in the longevity and long-term fi xation of the implant components, while the main patient challenges relate to the preservation of function and quality of life over time. Since 1995, the Trial Bureau of the Department of Orthopaedic Surgery has been responsible for the design, setup, and follow-up of clinical research. The major research theme is the assessment of implant fi xation and survival, particularly in view of the department’s long tradition with uncemented THA and TKA implants. It is our primary aim to assess how well implants function over time (revision rate/infection rate). As a secondary aim, we strive for optimal surgical techniques and patient care and in doing so investigate new technologies and techniques. These include:1 assessment of potential ways to improve implantation techniques with new technologies (e.g. computer navigation) and new surgical approaches (e.g. minimally invasive surgery)2 assessment of failed implants to learn how to improve implant design and fi xation techniques3 improvement of conservative (i.e. non-surgical) interventions for hip, knee, spine and shoulder pathology 4 assessment of rehabilitation speed and quality/quantity of movement after THA, TKA, and spine surgery 5 assessment of patient satisfaction.

Orthopaedic biotechnology bridges the clinical area of orthopaedic surgery and developments within the fi eld of

biotechnology. These developments are aimed at supporting, replacing and repairing musculoskeletal tissue. Care is being taken to ensure that a continuum exists between fundamental research and clinical application.

(Epi)genetics Infl ammation In Situ Incubator

Nucleus prosthesis Spineguide Bone cement Scoliosis brace

Knee brace Insoles Chondrocyte Implantation Computer navigated TKP

Bioceramics Infections Novel coatings Hydroxy-apatite coated THP

Fundamental research Pre-clinical Clinical phase

Bioceramicsß-TCP-based ceramics are widely used in orthopaedic surgery (e.g. during

prosthesis implantation to achieve bony ingrowth and mechanical support). For large bone defects, however, ceramic-based anatomical reconstruction is not possible using the current technologies. Together with several partners, we have developed a 3D plotting process to print porous structures from a biodegradable ceramic paste that hardens in a cold cement reaction, enabling the incorporation of bioactives.

InfectionsAn infected total joint replacement is a devastating complication for the patient

and a costly one for the health system and society in general. In terms of orthopaedic surgery, implant infection is a serious adverse event often requiring revision surgery. In general, two types of infection can be distinguished: 1) direct postoperative wound infection, and 2) low-grade infection that develops over time. The incidence depends on the type of elective surgery and indication, but is observed on average between 0.5 and 4% of all orthopaedic surgical interventions. In the BioMedical Materials (BMM) NANTICO consortium we aim to develop and test a new antibacterial coating that can be applied on almost every metal implant available.


Novel coatingsThe plasma spray technique is a relatively diffi cult procedure to control,

performed under extremely high temperatures and results in thick, brittle coatings that occlude the deeper layers of the 3D surface textures, which are more open nowadays. Further, there is concern about long-term bone-implant coupling in the event of coating loss in suboptimal designs. Recently, however, new coating techniques (e.g. electrochemical deposition) have been developed for the processing of biomimetic (‘nature-like’) coatings, which are much thinner but nevertheless highly bioactive. They can be applied below body temperature onto and deeply into the porous implant surfaces. Because they allow for improved control of the coating characteristics (crystallinity, Ca-P ratio), the effects can be better regulated. This provides for deeper and tighter anchoring of implant to bone, as well as an almost complete sealing of the interfaces for wear particles.

Hydroxyapatite-coated total hip prosthesisFrom a patient’s perspective and in terms of cost effectiveness, total hip

arthroplasty (THA) has been the most successful type of operation ever. But the challenge remains of ensuring a long-lasting bond between implant and bone in order to prevent (or at least postpone) complicated revision arthroplasty. Since the late 1970s, important improvements have been realised in the choice of materials (for better biocompatibility), implant design (for improved mechanical stability and stress transfer to bone), surface texture (for deeper bone ingrowth) and bioactive coatings (for faster and more extensive fi xation to bone). In the area of osteoconductive coatings, the Department of Orthopaedic Surgery is an international pioneer, spearheaded by Professor Ruud Geesink in the 1980s. In particular, the application of hydroxyapatite by means of a plasma spray technique – an absolute novelty worldwide –resulted in the swift bonding of prosthesis to bone, with unequalled clinical results and implant survival.



Knee braceTo understand the pathogenesis of osteoarthritis and improve rehabilitation

strategies, it is critical to monitor the loading of the affected joint during daily activities and exercise. We develop and use technologies aimed at monitoring whole body activity and knee use (i.e. loads and activity) in an ambulant manner. Within the research project ‘Biosensing’, we will also develop an innovative modular system which integrates objective biomechanical parameters (e.g. knee joint forces, strength/activity, knee alignment) estimated and analysed using 3D gait analysis. Validated under gold-standard laboratory conditions by use of the 3D gait analysis (Vicon) system. This offers the possibility for 24-hour outpatient monitoring and wireless communication. It also provides 3D characteristics of the knee joint, integrated EMG and recognition and differentiation between types of activity. Thus, the project holds promise to determine possible correlations between biomechanical variables and the progression of osteoarthritis.

InsolesThe traditional method of measuring and constructing orthopaedic footwear is

a time-consuming process. It relies necessarily on trial and error, as footwear and insoles are frequently modifi ed during the treatment on the basis of personal insight without scientifi c foundation. In Footfuse, a ‘Pieken in de Delta’ project from 2006, an industrial and predictable method for measuring and producing therapeutic insoles was developed. The data set derived from this study has been used to create a foot model that demonstrates the effects of the insole shape on movement and load. When combined with 3D scanning techniques and plantar pressure measurements in a automated production process, new insoles can be manufactured more rapidly and far more cheaply.

Chondrocyte ImplantationAt present, promising steps are being taken in cartilage repair. Small parts of still-

healthy joint cartilage are harvested, cultured in a laboratory, then later transplanted into the cartilage defects of patients’ knees. The Department of Orthopaedic Surgery in Maastricht is involved in a multicentre study (the Matrix Assisted Chondrocyte Implantation) to compare this method of cartilage repair with older, more established techniques (e.g. microfracture). Currently, the new procedure is only possible for specifi c cartilage defects, and thus cannot be used to treat all arthritic knees.

Computer-navigated total knee prosthesisKnee prosthesis has evolved rapidly in design over the last ten years. Currently,

much focus is being placed on better instrumentation, different materials and coatings (i.e. the layer on the prosthesis that enhances the bone ingrowth of the components) and improvements in implant placement. Computer navigation has been used for many years during total knee prosthesis implantation. This allows for more accurate placement and results in fewer postoperative complaints, speedier recovery and better long-term implant survival.


EpigeneticsIn addition to genetic information, cells also carry epigenetic (Greek; epi = up,

above) information: nuclear DNA is not naked, but tightly packed in chromatin. Use of genetic information (gene expression) requires changes in chromatin structure; the degree of chromatin compaction determines whether transcription factors have access to DNA or not. We focus specifi cally on Polycomb Group (PcG) proteins, a class of chromatin ‘packers’. We discovered that PcG proteins play an important role in fi netuning transcription and DNA replication activities during chondrogenesis. In addition, we found that immediate early genes (including EGR1) can play a novel role in opening chromatin in the context of chondrogenesis. Loss of EGR1 deregulates central chondrogenic master genes and affects PcG function.

Infl ammationCartilage development, or chondrogenesis, is a cellular differentiation process that

starts with mesenchymal progenitor cells that differentiate into adult chondrocytes typically expressing collagen type II. Chondrogenesis of the growth plate ends at the hypertrophic phase, which is marked by collagen type X expression. After this phase, the cells die and osteocytes infi ltrate the remaining matrix. For unknown reasons, healthy articular cartilage does not show the transition to hypertrophy. Chondrocyte hypertrophy and subsequently, ossifi cation are major complicating factors in cartilage regenerative techniques. We hypothesised that COX inhibition of the infl ammation proteïne cyclooxygenese can be used as a molecular tool to modulate cartilage development. Therefore, we studied the specifi c function of COX-2 during chondrogenesis. Our fi ndings showed that inhibition of COX-2 from the onset of differentiation had an inhibitory effect only on the hypertrophic phase of chondrogenesis. Inhibition in later phases of cartilage development, however, stimulated chondrogenesis. These fi ndings will improve our knowledge about the function of COX-1 and COX-2 during different stages of cartilage formation and may help to improve the outcome of cartilage regenerative techniques.


Chondrogenic modelsHealing of cartilage defects is still a major clinical problem. Most defects do not

heal spontaneously and can eventually lead to osteoarthritis. To improve cartilage healing, much effort is being put into fundamental cellular research. A cellular system should have all aspects of cartilage development (e.g. synthesis of cartilage specifi c biomolecules) and to study every important aspect of cartilage development it should be possible to manipulate the system pharmaceutically and genetically. One of the best characterised chondrogenic cell lines is the ATDC5 cell line. This mesenchymal precursor cell can be stimulated for chondrogenic differentiation by proper stimuli. To enable the transition from in-vitro to in-vivo, we set up an ex-vivo culture system. We succeeded in culturing sections from periosteal tissue and differentiating these into cartilage. The series of chondrogenic models ranges from in-vitro cell lines via primary in-vitro models to ex-vivo tissue culture. It enables us to test in-vitro fi ndings on systems that better resemble the actual clinical situation.

In Situ IncubatorTreatment of full-thickness damage to hyaline cartilage is hampered by the limited

availability of autologous healthy cartilage and the lengthy, costly cell isolation and expansion steps associated with autologous chondrocyte implantation (ACI). We therefore developed a strategy for de-novo engineering of ectopic autologous cartilage (EAC) within the sub-periosteal space (In Situ Incubator, or ISI). This novel method for generating EAC is supported by the Dutch Reumafonds. Formation of EAC was achieved without transplantation of cells and can even be achieved without administration of growth factors. Both in-vitro and in-vivo, hypoxia seems to play an important role in inducing periosteal chondrogenesis. The use of EAC derived from the ISI is a promising method for repairing chondral and osteochondral defects (e.g. osteochondritis dissecans).


Nucleus prosthesisThe intervertebral disc is a complex structure with several relatively distinct

components: the nucleus pulposus, the annulus fi brosus and the vertebral end plates. Synthetic hydrogel biomaterials have been developed to create a biomimetic prosthesis for the intervertebral disc (with a focus on the nucleus pulposus). During the past four to fi ve years, the MUMC+ has developed a new experimental nucleus prosthesis. The device is based on a new, biocompatible hydrogel with engineered properties that mimic the physical-mechanical characteristics of the normal, healthy nucleus. The new biomaterial has two additional features: 1) it readily absorbs water and 2) it is radiopaque, so it can be visualised using X-ray. With regard to the intervertebral disc, the Department of Orthopaedic Surgery is now participating in the BioMedical Materials (BMM) IDiDAS consortium, a collaborative project for the further development of intervertebral disc prosthesis.

SpineguideSpinal deformities are usually the result of (congenital) impaired development

of the vertebral bodies. Current approaches attempt to rectify the deformity but are restricted with respect to postoperative mobility and show mechanical failure such as fatigue and static fractures. The Department of Orthopaedic Surgery is now collaborating with DSM’s Dyneema group to test and develop a spinal cable and fi xation system using Dyneema Purity® cable constructs. This project is known as SpineGuide and aims to preserve mobility and growth while providing suffi cient stability in correcting spinal deformities.


Bone cementWith the ageing of the population, the prevalence of osteoporotic vertebral

fractures is increasing. These fractures can cause considerable pain and deteriorate physical and mental wellbeing in the elderly population. Percutaneous, transpedicular injection of bone cement can stabilise the fractured vertebral body and thus relieve pain. This new, minimally invasive operative treatment is being performed by the Department of Orthopaedic Surgery. In addition, a novel radiopaque bone cement developed at Maastricht University is being tested in the laboratory. If successful, it may be used in clinical practice in the near future.

Scoliosis braceScoliosis is a curvature of the spine from side to side that can result in disability and

a heavy psychological burden for the patient. Traditionally, patients are treated with heavy, rigid braces that are both marked and inconvenient. In collaboration with TNO, Welldesign, IDEE and Orthopedie 2000, the Department of Orthopaedic Surgery has developed a new brace with more fl exibility, an active tightening assistance component and strap tension fastening that follows a special force pattern. The new brace enhan-ces comfort considerably, and will be tested for its effi cacy to control the deformity by way of pressure measurements and radiographic evaluation.


Medical Field Lab‘The gaining of knowledge is in its application’

Most university medical centres recognise the need to drive the growth of innovation but few are adequately equipped for this purpose. Even when internal development resources are fully employed, it still may be diffi cult to produce suffi cient innovation quality and output excellence to meet business goals. The MUMC+ has developed a unique concept to facilitate the development of innovative products and services dedicated to optimal clinical application: the Medical Field Lab (MFL). The MFL initiative was established in 2006 as a project within the MUMC+’s Department of Orthopaedic Surgery. It began with an ambitious cluster project dedicated to ‘personalised’ high-tech medical devices. The cluster encompassed three innovative sub-projects: an interactive scoliosis brace, customised bioceramic implants and customised insoles through rapid prototyping.

Since October 2008 the MFL has existed as a limited liability company within the MUMC+ organisation. Its innovation activities focus on producing market-oriented health products that generate social, economic and scientifi c value. The MFL acts as a hub for an internal network of clinicians and researchers and an external network of SMEs, multinationals, knowledge institutions and societal organisations. Its core business is project building, project management and fundraising. Currently, the MFL is seen as a promising platform to facilitate academically grounded innovation and technology transfer.

Medical Field Lab BV

Maastricht Universitair Medisch CentrumP. Debyelaan 25Postbus 58006229 HX Maastricht

T: +31 (0)43 387 50 31E: medicalfi [email protected]: www.medicalfi eldlab.nl

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This publication was fi nancially suported by:

Department of Orthopaedic SurgeryUniversity Hospital MaastichtPO Box 58006202 AZ MaastrichtT: +31-43-3875038F: +31-43-3874893E: [email protected]: WWW.biotecmaastricht.nl

In de collegecyclus brengen we onder-zoek, behandeling in het ziekenhuis en maatschappelijke vragen dichter bij elkaar. Naast een overzicht van de nieuwste behandeltechnieken krijgt u inzicht in diverse onderzoeks-richtingen en leggen wij u onze visie voor over hoe behandelingen er in de nabije toekomst zouden kunnen uitzien. Er is gelegenheid tot interactie, we horen graag uw mening.

De colleges zijn vrij toegankelijk. Reserveren is niet mogelijk, maar gezien het beperkt aantal plaatsen adviseren wij u tijdig aanwezig te zijn.

Middagcolleges: 16.00 - 17.30 uur

Locatie maandag t/m woensdagmiddag: Greepzaal azM / niveau 4

Locatie donderdagmiddag: Personeelsrestaurant azM / niveau 1Adres: P. Debyelaan 25, 6229 HX Maastricht

Van 15 t/m 18 juni vindt in de hal van het ziekenhuis een interactieve exposi-tie plaats, over dezelfde onderwerpen als de collegereeks. Wij nodigen u uit kennis te nemen van de ontwikkelingen en tonen u de nieuwste operatie- en behandeltechnieken aan de hand van demo’s en posters. ‘s Middags zijn er interactieve sessies waarin u zelf diverse technieken kunt uitproberen: bijvoorbeeld een camera hanteren die bij operaties wordt gebruikt of een schroef plaatsen met behulp van de computer etc. Tevens kunt u met artsen en onderzoekers van gedachten wisselen over de nieuwe ontwikkelingen.

Avondcolleges: 19.00 - 20.30 uur

Locatie alle avonden: Aula UMAdres: Minderbroedersberg 4-6, 6211 LK Maastricht

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Uitnodiging

Keep on Moving15 juni 2009 t/m 18 juni 2009

Collegecyclus Orthopaedische Biotechnologie

www.biotecmaastricht.nl

Collegecyclus Expositie en zelf doen

Voor meer informatie verwijzen wij u naar de website: www.biotecmaastricht.nl

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Contact:azMSecretariaat OrthopaediePostbus 5800T: 043-387 50 38F: 043-387 48 93E: [email protected]: www.biotecmaastricht.nl

Elk college wordt 2 keer gegeven op 2 locaties:

Symposium Orthopaedische BiotechnologieCollegecyclus Orthopaedische Biotechnologie


Documents

boekwerk orthopedie def - BioTec Maastricht2 assessment of failed implants to learn how to improve implant design and ﬁ xation techniques 3 improvement of conservative (i.e. non-surgical)