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Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 134 - 134
1 May 2011
Von Roth P Radojewski P Matziolis G Duda G Perka C Winkler T
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Objectives: Skeletal muscle trauma leads to severe functional deficits. Present therapeutic treatments are unsatisfying and insufficient posttraumatic regeneration is a problem in trauma and orthopaedic surgery. Mesenchymal stem cell (MSC) therapy is a promising tool in the regeneration of muscle function after severe trauma. Our group showed increased contraction forces compared to a non-treated control group 3 weeks after MSC transplantation (TX) into a skeletal muscle trauma. In addition we demonstrated a dose-response relationship of the amount of MSC and force enhancement. We furthermore investigated the fate of the transplanted MSC labelled with very small iron oxide particles using 7 Tesla-MRI. Histological analysis revealed fusion events between existing myofibers but only to a low amount. The increase of muscle force can not be explained by these events only. Before further steps are taken the impact of paracrine effects and the homing to the site of trauma of the MSC has to be evaluated. Experimental studies about the functional regeneration of traumatized skeletal muscule after systemic MSC-TX do not exist.

Methods: 36 female SD-rats received open crush trauma of the left soleus muscle. One week after trauma 2.5 x 106 autologous MSC, harvested from tibial biopsies, were transplanted intraarterially (i.a., femoral arte-ria, group 1) or intravenously (i.v., tail vein, group 2) (n=18). Control animals received saline (i.a.: group 3; i.v.: group 4) (n=18). Histological analysis and biomechanical evaluation by in vivo muscle force measurement was performed 3 weeks after TX.

Results: Twitch stimulation of the healthy right soleus muscles resulted in a contraction force of 0.52±0.14 N. Forces of tetanic contraction in the uninjured muscles reached 0.98±0.27 N. The i.a. MSC-TX improved the muscle force of the injured soleus significantly compared to control (twitch: 82,4%, p=0.02, tetany: 61.6%, p=0.02). Contraction forces of muscles treated i.v. (MSC vs. saline) showed no significant difference. The histological analysis showed no differences in the amount of fibrotic tissue.

Conclusions: The presented study demonstrates the effect of systemic MSC-TX in the treatment of severe skeletal muscle injuries. Interestingly, the functional regeneration could only be increased by i.a. application. The entrapment of MSC in the lungs and the dilution effect in the circulation, when injecting the MSC i.v. could be the reason. For possible future therapeutic approaches a systemic application is considered to be favourable compared to local injections due to the better distribution of the cells in the target muscle.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 622 - 622
1 Oct 2010
Winkler T Duda G Matziolis G Perka C Tohtz S Von Roth P
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Skeletal muscle injuries often lead to severe functional deficits. Mesenchymal stem cell (MSC) therapy is a promising but still experimental tool in the regeneration of muscle function after severe trauma. One of the most important questions, which has to be answered prior to a possible future clinical application is the ideal time of transplantation. Due to the initial inflammatory environment we hypothesized that a local injection of the cells immediately after injury would result in an inferior functional outcome compared to a delayed transplantation.

Twenty-seven female Sprague Dawley rats were used for this study. Bone marrow was aspirated from both tibiae of each animal and autologous MSC cultures obtained from the material. The animals were separated into three groups (each n=9) and the left soleus muscles were bluntly crushed in a standardized manner. In group 1 2×106 MSCs were transplanted into the injured muscle immediately after trauma, whereas group 2 and 3 received an injection of saline. Another week later the left soleus muscles of the animals of group 2 were transplanted with the same number of MSCs. Group 1 and 3 received a sham treatment with the application of saline solution in an identical manner. In vivo functional muscle testing was performed four weeks after trauma to quantify muscle regeneration.

Maximum contraction forces after twitch stimulation decreased to 39 ± 18 % of the non injured right control side after crush trauma of the soleus muscles as measured in group 3. Tetanic stimulation showed a reduction of the maximum contraction capacity of 72 ± 12 % of the value obtained from intact internal control muscles. The transplantation of 2 x 106 MSCs one week after trauma improved the functional regeneration of the injured muscles as displayed by significantly higher contraction forces in group 2 (twitch: p = 0.014, tetany: p = 0.018). Local transplantation of the same number of MSCs immediately after crush injury was able to enhance the regeneration process to a similar extent with an increase of maximum twitch contraction forces by 73.3 % (p = 0.006) and of maximum tetanic contraction forces by 49.6 % (p = 0.037) compared to the control group.

The presented results underline the effectivity of MSC transplantation in the treatment of severe skeletal muscle injuries. The most surprising finding was that despite of the fundamental differences of the local environment into which MSCs had been transplanted, similar results could be obtained in respect to functional skeletal muscle regeneration. We assume that the effect of the MSC after immediate injection can partly be explained by their known immunomodulatory competences. The data of our study provide evidence for a large time window of MSC transplantation after muscle trauma.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 70 - 70
1 Mar 2010
Lienau J Schell H Schmidt-Bleek K Perka C Bail H Duda G
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*Winner of ISFR Young Investigator Award

Purpose: The aim of this study was to compare the temporal expression pattern of factors related to cartilage and bone formation and endochondral ossification during standard and delayed bone healing for a more in-depth understanding of the molecular basis of disturbed bone healing and to elucidate suitable timing for substitution of factors to stimulate the healing process.

Methods: A tibial osteotomy was performed in two groups of sheep (n=30 each) and stabilized with either a rigid external fixator leading to standard healing or with a mechanically critical one leading to delayed healing. Hematoma/callus tissue was harvested 4, 7, 14, 21 and 42 days postop. qPCR was employed to determine the expression patterns of BMPs and other molecules.

Results: Gene expressions of BMP2, BMP4, BMP7, Noggin, MMP9 and MMP13 were distinctly lower in the delayed compared to the standard healing group at several time points from day 14, whilst no differential gene expression of Coll II and Coll X was found between both groups. Among the BMPs, BMP7 showed the most markedly differential expression. The first evident difference in BMP7 expression between both groups was found at day 14 suggesting that exogen substitution in the context of a therapeutic approach should be postponed. The differential expression pattern of both MMP9 and MMP13 suggests that there might be a failure or delay in endochondral ossification in delayed bone healing.

Conclusion: Downregulation in gene expression of osteogenic BMPs and cartilage matrix degrading MMPs may account for a considerable delay of bone healing.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 123 - 124
1 Mar 2009
Matziolis G Krocker D Tohtz S Perka C
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While significant component malalignment in the frontal and sagittal plane may lead to early loosening and pain, even small errors in the rotational component alignment are not tolerated due to its complex impact on knee joint kinematics and especially the patella tracking. It is accepted that navigated implantation of total knee arthroplasties improves accuracy in the frontal plane but it is yet unclear weather navigation leads to a more precise rotational component alignment. The study evaluated the influence of navigated implantation on femoral and tibial component alignment.

In a prospective randomized study 32 navigated and 28 conventionally implanted total knee arthroplasties were evaluated through a postoperative CT scan. In all cases the femoral component was referenced to the surgical epicondylar axis and the tibial component was referenced to the medial third of the tibial tuberosity. The angles between these bone landmarks and the components were measured on the CT scans and compared between both study groups.

The rotational malalignment of the femoral component in the conventional operating technique was 0.1° ± 2.2° (range 3.3° of internal rotation and 5.0° of external rotation). Navigated implanted femoral components showed a malalignment of 0.3° ± 1.4° (range 4.7° of internal rotation and 2.2° of external rotation), the difference was not significant. The rotational malalignment of the tibial component in the conventional technique was 7.5° ± 6.0° (range 27.1° of internal rotation and 15° of external rotation). Navigated implanted tibial components showed a malalignment of 6.9° ± 4.7° (range 21.2° internal rotation and 11.0° external rotation), the difference was not significant.

In conclusion the use of a navigation system did not improve the rotational alignment of the tibial or femoral component if only one bone landmark was used. Taking the relatively small errors of a navigation machine into account the error is attributable to the surgeon, who seems to be unable to precisely define bone landmarks. More than one landmark (e.g. additionally Whiteside’s line, posterior condyles, flexion gap for the femur and ankle joint for the tibia) should be used to define the component rotations. Consideration of different rotational landmarks is best done with a navigation system that, in contrast to the manual technique, has the possibility to show the degree of deviation of the components from each landmark.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 145 - 145
1 Mar 2009
Perka C
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Total hip arthroplasty is a challenging problem in case of high hip dislocation. In order to reduce the hip, a femoral shortening osteotomy is necessary to prevent damage to the neurovascular structures. In this study we present the mid-term results of a simple technique of simultaneous derotating and shortening osteotomy of the femur without the necessity of additional osteosynthesis.

In this retrospective study we included 28 patients with high hip dislocation. In these patients 30 consecutive cementless primary total hip arthroplasties with femoral shortening osteotomy were performed. 20 cases were previously operated. All patients were clinically and radiologically followed up after a mean of 4.5 years (range 2 – 5.7 years). Time point of consolidation was determined on consecutive radiographs for each patient.

The average operative time was 116 minutes (range 65 to 150 minutes). There were no intraoperative complications. Postoperatively no femur fractures, no pseudarthroses and no pareses were observed. The mean consolidation time of the osteotomy was 4.4 months. At the time of follow-up, one aseptic loosening had been verified. In this case a very small stem (size 03) had been used. The mean Merle d’Aubigne score for the unrevised hips improved from 8.2 points preoperatively to 15.1 points at follow-up.

In conclusion the presented technique allowed an easy and fast implantation of total hip arthroplasty in patients with high hip dislocation. The Zweymueller stem design with its rectangular cross-section seems responsible for the sufficient stability of the osteotomy resulting in a short consolidation time. Any additional osteosynthesis is obsolete. This leads to additional advantages including a short duration of surgery and a low complication rate. The good clinical results are attributable to the fact, that by shortening the femur, the physiological hip joint biomechanics could be approximated. The mid-term results of the described technique are very promising.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 154 - 154
1 Mar 2009
Dynybil C Schmidt C Backstroem M Schlichting K Duda G Perka C
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Introduction: Selective COX-2 (Cyclooxygenase-2) inhibitors have been found to impede fracture healing. The effect of selective COX-2 inhibitors on tendon healing in a bone tunnel, however, is unknown.

Methods: The authors performed bilateral anterior cruciate ligament reconstructions in 32 rabbits and used peripheral quantitative computed tomography (pQCT) to compare tendon-to-bone healing between tunnel aperture and midtunnel regarding bone mineral density (BMD) and ingrowth of new bone. Each animal was assigned to one of four groups. Two groups received selective COX-2 inhibitors orally for 3 weeks (Cele-coxib; 10 mg/kg/d), the two other groups received no COX-2 inhibitors (controls). The animals were sacrificed 3 and 6 weeks after surgery. In biomechanical testing maximum load to failure and stiffness of the tendon grafts were calculated from the load displacement curve and failure modes were recorded. To assess indirectly the effect on local COX-2 activity the synovial content of Prostaglandin E2 (PGE2), the major metabolite of arachnidonic acid metabolism and catalyzed by COX-2, was measured by Enzyme-linked Immunosorbent Assay (ELISA).

Results: Animals treated with selective COX-2 inhibitors had significantly lower BMD at the tunnel aperture (P=.02). In all groups the BMD at the tunnel aperture was significantly higher in comparison with the midtunnel (P< .05). In the controls ingrowth of new bone was greater at the tunnel aperture at 3 weeks (P=.028). After 3 weeks of COX-2 inhibitor administration synovial fluid concentrations of PGE2 were significantly lowered (P=.018) and increased more than threefold by 6 weeks after surgery and 3 weeks after last drug administration (P=.022), while in the controls there was a decrease in PGE2 between week 3 and 6. At 6 weeks the controls exhibited a twofold increase in maximum load to failure (3 weeeks: 28.2±20.9 N; 6 weeks: 59.6±53.6 N; P=.394), whereas the COX-2 inhibitor treated specimens decreased 1.9fold (3 weeks: 69.3±50.5 N; 6 weeks: 37.4±16.8 N; P=.24). Maximum load to failure values correlated with PGE2 changes, but not statistically significant (r2= −0,502; p=0,056). Failure modes at 3 and 6 weeks were rupture and degloving, respectively, of the tendon graft.

Discussion: This study revealed decreased bone mineral density at the tunnel aperture at 3 weeks, an increase of the inflammatory mediator PGE2 and decreased graft stability with time after treatment with selective COX-2 inhibitors. Untreated controls appeared to have a more physiological healing course with a continuous decrease in PGE2 and an increase in graft stability. Our results suggest, that selective COX-2 inhibitors may delay tendon healing in a bone tunnel.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 155 - 155
1 Mar 2009
Winkler T von Roth P Schumann M Sieland K Taupitz M Perka C Duda G Matziolis G
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Background: Autologous mesenchymal stem cells (MSC) have been shown to improve the functional outcome after severe skeletal muscle trauma. The reasons for this improvement have yet not been revealed. Up to now insufficient techniques of cell labelling, which could only be used for histologic analysis ex vivo, have been a problem.

The development of iron oxide nanoparticles, which are taken up and endosomally stored by stem cells, allows the evaluation of cellular behaviour in the muscle with the use of magnetic resonance imaging (MRI). Previous work has shown that labelling does not affect the proliferation and neurogenic differentiation capacity of embryonic stem cells. In the present study we are currently investigating the in vivo distribution and migration of locally transplanted MSC after blunt muscle trauma in a rat model.

Methods: MSC cultures are derived from tibial biopsies of Sprague Dawley rats via plastic adherence. A standardized open crush injury of the left soleus muscle is performed in each animal. 24 hours before transplantation cells are labelled with very small superparamagnetic iron oxid particles (VSOP-C200, Ferropharm, Teltow, Germany) and Green Fluorescent Protein (GFP). One week after trauma different amounts of stem cells (5×105, 1×106 and 5×106) are transplanted into the soleus muscle by local injection. Distribution and migration of the cells are evaluated over time by the repeated performance of high resolution-MRI at 7 Tesla (Bruker, Rheinstetten, Germany). At the endpoint of the study, three and six weeks after transplantation, the muscles are harvested and histologically and immunohistochemically analysed.

Results: Cells could be visualised inside the soleus muscle in the MRI 24 hours after transplantation showing characteristic signal extinctions in T2*-weighed images. The hypointense signal could be followed over the longest investigated time of six weeks and could be easily discriminated from the structures of the injured muscle. Preliminary results show that the cell pool changed its shape over time with the loss of an initially depicted injection canal and an increase in the surface/volume ratio. First histologic Prussian Blue stained sections showed co-localisation of the respective MRI signal and nanoparticle labelled cells. Fusion events of marked cells with regenerating myofibers could be observed.

Conclusion: Magnetic labelling of MSC is a powerful tool to analyse the in vivo behaviour of the cells after transplantation into a severly injured skeletal muscle. For the first time the observation of an intraindividual time course of the distribution of the transplanted cells is possible. Our preliminary results are promising and the ongoing work will further characterise migration processes and the correlation of the MRI results with muscle function evaluated by contraction force measurements.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 156 - 157
1 Mar 2009
Winkler T Matziolis G Schumann M Stoltenburg-Didinger G Duda G Perka C
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Background: Scientific investigation of muscle trauma and regeneration is in need of well standardised models. These should mimic the clinical situation and be thoroughly described histologically and functionally. Existing models of blunt muscle injury are either based on segmental muscle damage or in case of whole muscle injury also affect the innervating structures. In this study we present a modified model of open crush injury to the whole soleus muscle of rats sparing the region of the neuromuscular junctions.

Methods: The left soleus muscles of male Sprague-Dawley rats were crushed with the use of a curved artery forceps. Functional regeneration was evaluated 1, 4 and 8 weeks after trauma (n = 6 per group) via in vivo measurement of muscle contraction force after fast twitch and tetanic stimulation of the sciatic nerve. The intact right soleus muscle served as an internal control. H & E staining was used for descriptive analysis of the trauma. The amount of fibrosis was determined histomorphologically on Picro-Sirius Red stained sections at each point of time.

Results: Across the evaluated regeneration period a continuous increase in contraction force after fast twitch as well as after tetanic stimulation could be observed – describing the functional regeneration of the traumatized soleus muscle over time. Tetanic force amounted to 0.34 ± 0.14 N, which are 23 ± 4% of the control side one week after trauma, and recovered to 55 ± 23% after eight weeks. Fast twitch contraction was reduced to 49 ± 7% of the control side at one week after injury and recovered to 68 ± 19% during the study period. Fibrotic tissue occupied 40 ± 4% of the traumatized muscles after the first week, decreased to approximately 25% after four weeks and remained at this value at eight weeks.

Conclusion: The trauma model characterised morphologically and functionally in the presented study allows the investigation of muscle regeneration caused by highly standardized injury exclusively to muscle fibers.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 55 - 55
1 Mar 2006
Perka C Schröder J
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Introduction: Total hip arthroplasty is problematical in the case of high hip dislocation. To reposition the hip, a femoral shortening osteotomy is necessary in order to prevent damage to the neurovascular structures. This paper describes the implantation of a small threaded cup and a cementless straight stem using a simple technique with a simultaneous, derotating and shortening osteotomy for the femur.

Materials and Methods: In this study, 30 cementless primary total hip arthroplasties were performed in 27 patients with high hip dislocation, and clinically assessed at a mean follow-up of 5.1 years. Acetabular reconstruction was done with a cementless threaded cup, whereby the cup was medialized to ensure that at least one thread was anchored in the bone in order to achieve good primary stability. All radiographs were analyzed retrospectively.

Results: A femoral shortening osteotomy was performed in all cases. The average duration of surgery was 116 minutes. One cup loosening and one stem loosening was observed. Kaplan-Meier survivorship analysis, with aseptic radiological loosening as the endpoint, predicted a survival rate of 96,6% at 5.1 years for the acetabular component and 96.6% for the stem. The mean Harris hip score for the unrevised hips improved from 28.7 points preoperatively to 81.2 points postoperatively. Femur fractures, pseudoarthroses, paresis and deep infections were not found.

Conclusion: The surgical technique described enables the initial stable fixation of a threaded cup in the small acetabulum and of a standard prosthesis without additional osteosynthesis for the performed osteotomy. Additional advantages include a shorter duration of surgery, a lower complication rate and a more rapid consolidation of the osteotomy in comparison to other techniques. Despite a patient group with a low average age and comparatively high daily activity, hip reconstruction with a cementless, threaded cup and the use of a cementless, straight stem without additional osteosyn-thesis has produced a good mid-term outcome.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 130 - 130
1 Mar 2006
Tuischer J Matziolis G Krocker D Duda G Perka C
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Background Osteopontin (OPN), also known as bone sialoprotein I or secreted phosphoprotein 1, is a major non-collagenous bone matrix protein. A broad distribution has been detected in embryonic bone, osteoid, and fracture callus [Nomura et al. 2000] pointing out its central role in bone development and healing. It remains unclear weather mechanical conditions influence OPN synthesis and thereby osteoprogenitor cell differentiation. We investigated OPN mRNA-levels of bone marrow derived mesenchymal stem cells (bm-MSC) cultured in a previously described compression bioreactor (CBR) [Matziolis et al. under review] under dynamic compression (DC).

Materials Bm-MSCs of 5 different individuals (mean age 61y) were seeded in a fibrin-alginate mix-matrix placed between two slices of lyophyliced cancellous bone. One group of constructs (n=10) underwent DC with 7kPa at 0.05 Hz, resulting in a matrix compression of 1mm at an heigh of 5mm, for 24 hours in the CBR. Constructs cultured under similar conditions but without DC served as control group (n=10). mRNA was extracted out of each construct after ending the DC, following the Trizol®-protocol. After cDNA-synthesis, GEArray Q series (Human Osteogenesis Gene Arrays) were performed and normalized versus GAPDH.

Results We found an increase of OPN-expression in all dynamically compressed matrices. In the DC-group we found a mean of 5-fold increase of OPN mRNA compared to the control group (median: 0.43 vs. 0.09, p< 0.001).

Discussion and Conclusion The results of this study demonstrate that an in vitro DC of bm-MSCs for 24 hours leads to an increased expression of OPN. We conclude that DC is an important element of early fracture healing by increasing the expression of OPN and thereby modulating progenitor cell differentiation immediately after mechanical instability caused by a fracture.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 60 - 60
1 Mar 2006
Perka C Heller M Taylor W Duda G
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The hypothesis of the current study was that the loading of the proximal femur is altered significantly by the surgical approach. The change in long-term periprosthetic bone mineral density in relation to the alteration of the musculature after the anterolateral (Group A) and transgluteal approaches (Group B) has been compared. Group A comprised 35 hip joints (30 patients) and Group B 47 hip joints (37 patients). No significant differences were seen between groups in respect to age, gender, or diaphyseal BMD distribution and in respect to average stem size in a Wilcoxon test. Measurement of BMD in femoral Gruen Zones I, II, VI, and VII revealed a significant bone loss in Group B compared with Group A; however the functional outcome showed no significant differences between the two groups postoperatively. Analysis of proximal femoral loading by means of a validated musculoskeletal model showed a considerable redistribution of the musculoskeletal loading across the hip during walking and stair climbing after a transgluteal compared with an anterolateral surgical approach. The muscular damage caused by the surgical approach seems to have a significant influence on the long-term bone loss and the initial postoperative loading of the proximal femur.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 26 - 27
1 Mar 2006
Perka C Katterle H Drahn T Matziolis G
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Introduction: The objective of the study was to test the hypothesis that revision total hip arthoplasty in cases with extensive acetabular bone defects performed with a newly developed, conical, titanium, ribbed shaft socket designed for cementless press-fit into the dorsocranial ilium would not demonstrate inferior outcomes using literature controls.

Methods: 38 consecutive hips had an acetabular revision with a pedestal cup. All of the patients had a type IIIa or IIIb defect according the Paprosky-classification. There was an average follow-up of 4.2 years, with a range of 3 to 6 years. Two patients died, one patient was lost to follow-up. All patients were evaluated radiographically, by CT-Scan and clinically.

Results: At the time of follow-up, 32 (91.4%) cups were stable. Aseptic loosenings occured in one case, septic loosenings occured in 2 cases. The average Harris Hip Score improved from 43 points (range: 16–78 points) preoperatively to 82 points (range 56–98 points) postoperatively. Complications included four dislocations without recurrency. The guide instrument facilitates correct anchorage in the dorsal ilium in all cases.

Conclusion: The presented findings show the short-term efficancy of the procedure with respect to implant fixation and clinical results in large acetabular defects, but longer follow-ups and a larger number of patients are needed before the durability of this reconstructive technique can be assessed. The implant allows restoration of the correct centre of rotation, equalization of leg length and optimization of the strength of the hip abductors. Our results should be considered encouraging.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 94 - 94
1 Mar 2006
Dynybil C Tobler M Schlichting K Schmidt C Perka C Weiler A
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Objectives: The replacement tissue used for anterior cruciate ligament reconstruction undergoes extensive biologic remodelling and incorporation after implantation. These changes, in which the tendon loses some of its characteristic features and adopts those typically associated with ligaments, has been referred to as ligamentization. The purpose of this study was to identify the proinflammatory response in the healing graft in the early phase.

Methodes: Twenty New Zealand White Rabbits underwent ACL reconstruction with a semitendinosus tendon. Animals were sacrificed at 3 and 6 weeks. The harvested tissue including parts of remaining grafted tendon and genuine anterior cruciate ligament at time of the surgery as well as the tendon graft withdrawn at sacrification were prepared for immunohistochemical, histomorphometry and electromicroscopical analysis; synovia samples were taken at the sacrification as well. The tissues were immunostained for IL-1beta, TGF-beta, TNF-alpha (induction of inflammatory cascade), COX-2 (mediator of inflammatory response), Matrix Metalloproteinases (MMP-1, MMP-3, MMP-13, matrix destructive enzymes), TIMP-2 (Tissue Inhibitor of MMPs); the PGE2 (mediator of inflammatory response) content in the synovia was quantified by ELISA.

Results: At 3 weeks after surgery the COX-2+ cells accounted for 70% of all cells present in the graft tissue, and decreased to 28% at 6 weeks. Similar, IL-1beta+ cells within the tendon decreased from week 3 to week 6. Controversly, there was an increase of COX-2, IL-1beta and MMP-1 in the intercellular tissue. The numbers of COX-2+ cells and IL-1beta+ cells at 3 weeks as well as the intercellular area stained positiv for COX-2, IL-1beta and MMP-1 at 6 weeks were significantly larger compared to the genuine ACL (p =< 0.05). At 3 weeks some cells stained positiv for MMP-3 and MMP-13, but not at 6 weeks. There was a slight pericellular staining for TIMP-2 at 3 weeks. TGF-beta+ cells and TNF-alpha+ cells were almost not detectable at every time point. Thus, proinflammatory cytokines and MMPs were synthesized in the early phase after ACL reconstruction by the tendon cells and accumulated at 6 weeks in the intercellular tissue.

Conclusions: In the early phase of the graft healing after ACL reconstruction, there was a signifikant increase in proinflammatory cytokines and matrix destructive enzymes in the tendon graft. With the capability of synthesizing cytokines, tendon cells may play a critical role in tendon healing at early time points. Facing the widespread use the bias of cox-2 inhibitors on these immunologic processes has to be checked. Activating matrix destructive enzymes, cytokines appear to be crucial for connective tissue remodelling and graft stability after ACL reconstruction.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 148 - 148
1 Mar 2006
Funk J Gross C Disch A Schneider S Tohtz S Perka C Putzier M
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The objective of this study was to evaluate the suitability of autologous periosteal cells for spinal fusion in humans. Lumbar spondylodesis has a slow consolidation rate with a consecutive lengthy period of inability to work and the risk of non-union. This study evaluates the applicability of a cell-matrix construct for spinal fusion using clinical and radiological parameters.

All experiments were approved by the university ethics committee. Lumbar spondylodesis of the segments L4/5 or L5/S1 was performed in 20 healthy patients (mean age 45 years). Indication for surgery was DDD resistant to conservative treatment. 10 weeks before fusion operation, a piece of periosteum was harvested from the proximal tibia of the patient. The material was chopped and digested. In the washed cell suspension cell number and viability were determined. The viability was greater 90% before seeding. After four passages, the cells were mixed with human fibrinogen, and soaked into polymer fleeces. Polymerization was achieved by adding thrombin. The 3D constructs were cultured for 3 weeks. The final application form were chips of 2mm thickness and 8mm diameter. Spondylodesis was performed using a ventral approach for implantation of 2 titanium cages and a dorsal approach for application of a transpedicular screw-rod system (Medtronic, Sofamor Danek). In 10 patients the chips were implanted ventrally within the cage. The other 10 patients obtained a dorsal intertransverse transplantation of the chips. Pre-operative, 3, 6, 9, and 12 months after surgery a clinical examination was performed, radiographs, and functional scores were obtained.

No implant associated side effects were noted. Especially, signs of infection or allergic reaction have not been observed. The harvest sites of all patients presented symptom-free after 3 months. The rate of consolidation was 60% after 6 months, 90% after 9 months, and 100% after 12 months. No clinical or radiological signs for implant failure or malpositioning were observed. 90% of the patients were satisfied with the outcome of the surgery.

Cultured autologous periosteal cells are a suitable material for anterior as well as posterior spinal fusion in humans. They may accelerate the rate of fusion and reduce the risk of non-union. Rate and velocity of osseous consolidation need to be compared to that of patients treated with iliac crest autograft. A major advantage might be the lower rate of graft site morbidity.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 64 - 64
1 Mar 2006
Schroeder J Morawietz L Matziolis G Leutloff D Gehrke T Krenn V Perka C
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Despite all gain of knowledge, septic and aseptic loosening of endoprostheses still remain unsolved problems. In loosening of joint arthroplasty a periprosthetic membrane is found between the bone and the loosened implant. The characteristics of the membrane are influenced by the process that leads to the loosening of the endoprosthesis. The aim of the study was to introduce a classification system that enables a standardized diagnostic evaluation and helps to determine the aetiology of the loosening process.

Based on histomorphological criteria and polarized light microscopy, four types of periprosthetic membranes were defined: periprosthetic membranes of the wear particle type (type I), periprosthetic membranes of the infectious type (type II), periprosthetic membranes of the combined type (type III), and periprosthetic membranes of the indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria.

The interobserver reproducibility was sufficient (95%). The correlation between histopathological and microbiological diagnosis was high (89%, p< 0,001). The four types of periprosthetic membranes showed a significantly different time of revision.

This classification system enables a standardized diagnostic procedure. It therefore is a basis for further studies concerning the etiology and pathogenesis of prosthesis loosening. The reliability of this histomorphological examination in diagnosing infections is currently reviewed.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 4 | Pages 560 - 564
1 Apr 2005
Disch AC Matziolis G Perka C

Bone-marrow oedema can occur both in isolation and in association with necrosis of bone, but it has not been shown whether each respond to the same methods of treatment.

We treated 16 patients with isolated oedema and 17, in which it was associated with necrosis of the proximal femur, with the prostacyclin derivative iloprost, which has been shown to be effective in the idiopathic form. The Harris hip score, the range of movement, the extent of the oedema as measured by MRI, pain on a visual analogue scale and patient satisfaction were recorded before and subsequent to treatment.

In both groups, we were able to show a significant improvement (p < 0.001) in these observations during the period of follow-up indicating that iloprost will produce clinical improvement in both circumstances.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 334 - 334
1 Mar 2004
Matziolis G Perka C
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Aims:We report our results with a Tantalum acetabular pressþt cup (Hedrocel), available since 1997. Although not coated its trabecular metal microstructure provides a good primary stability through a high friction against cancellous and cortical bone. An excellent bony ingrowth could be demonstrated in several animal experiments. Methods: 125 total hip arthroplasties were performed on 108 patients. All of them were followed up in a prospective manner 3, 6 and 12 months postoperatively. The outcome was quantiþed using the Harris hip and Merle dñAubigne scores and radiographic evaluation. Results: The Harris hip score raise from preoperative 44 to 87 after one year and the Merle dñAubigne score from 8 to 16. There were no signs of radiographic acetabular loosening. Sclerosis (Zone 1, 2 according to DeLee and Charnley) due to adaptation of the trabecular bone could be shown in most cases. The complication rate was on a low level (0.8% major, 3.2% minor complications) including 2 luxations, 2 relevant hematomas and 1 deep infection. Two cups had to be revised, one direct postoperatively for recurrent luxations due to an oversized inclination angle, the other for a deep infection. The infected cup was þrmly integrated, although it had to be explanted only a few weeks after implantation. Conclusions: Our results show, that the new Hedrocel acetabular cup has very good results with a good primary stability, a lack of radiographic loosening signs and an adaptation of the trabecular structures meaning a good osseous integration after one year. The long term results have to be obtained in the future.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 276 - 276
1 Mar 2004
Perka C Drahn T Katterle H
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Aim: The purpose of this study was to assess the results with use of a newly developed, conical, titanium, ribbed shaft socket designed for cementless pressþt into the dorsocranial ilium for revision total hip arthroplasty Methods: 25 hips had an acetabular revision with a pedestal cup (Centerpulse). All of the patients had a type III defect according the AAOS classiþcation. There was an average follow-up of 4.3 years, with a range of 3 to 5 years. One patient died during the study period. All patients were evaluated radiographically, by CT-Scan and clinically. Results: At the time of follow-up, 22 (91.7%) of 24cups were stable. Both loosenings affected patients with an low-grade infect. In this group none aseptical loosening occurred. The average Harris Hip Score improved from 41 points (range: 16–78 points) preoperatively to 84 points (range 56–98 points) postoperatively. Complications included four dislocations without recurrency. The radiological follow-up examinations revealed osteointegration of 21 implants. Conclusion: The presented þndings show the short-term efþcancy of the prcedure with respect to implant þxation and clinical results in large acetabular defects, but longer follow-ups and a larger number of patients are needed before the durability of this reconstructive technique can be assessed. Our results should be considered encouraging.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 284 - 284
1 Mar 2004
Hasart O Labs K Leutloff D Perka C
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Aim: The purpose of study was to analyse osseous changes of tibial spine in radiographs of knees with aplasia of cruciate ligament. Methods: 13 patients with aplasia of cruciate ligament and respective x-rays were examined and analysed. Diagnosis were proofen by MRI or Arthroscopy. Moreover we checked patients with anterior and complete aplasia of cruciate ligament (s) separately. Results: We found typical signs of hypolasia and aplasia of intercondylar eminence in radiagraphs which correlate with anterior or complete aplasia of cruciate ligaments. These changes we classiþed in 3 types. Conclusion: Using this classiþcation it is possible to get a strong indication for aplasia of cruciate ligament only on the basis of x-rays.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 275 - 275
1 Mar 2004
Perka C Tohtz S
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Aim: The purpose of this study was to assess the results with use of an oval cementless acetabular component for revision total hip arthroplasty. Methods: 30 hips had an acetabular revision with an cementless oval acetabular component. No patient was lost to follow-up, but one died during the study period. All defects were classiþed during surgery according the AAOS classiþcation. All patients were evaluated radiographically and clinically and were followed for an average of thirty-six months (range, twenty four to fourty eight months). In 21 of the 30 hips no additional bone grafting was necessary. Results: There were 17 segmental defects (type 1), 12 combined defects (type III) and one case of pelvic discontinuity (type IV). At the time of follow-up, 27 (93.1%) of 29 cups were stable. One of the loosening affected the patient with pelvic discontinuity, the other a patient with a combined segmental defect including the medial wall. The average Harris Hip Score improved from 39 points (range: 15–73 points) preoperatively to 89 points (range 68–96 points) postoperatively. Complications included three dislocations without recurrency. The radiological follow-up examinations revealed good osteointegration of 27 implants. All postoperatively remaining defects were completly þlled in by bone at the follow up. Conclusion: The asymmetrical shape of the BOFOR enhanced the primary stabilty on the lateral columns with three point anchorage. We recommend this device when a patient has an oblong-shaped acetabular defect and the surgeon wants to correct an elevated hip center. However, the medial wall of the acetabulum (Kohlerñs line) should be intact.