Research projects
Cartilage research
Malfunction of the knee joint is often associated with cartilage injury. Whether healing or restoration of lost or wounded parts of articular cartilage with newly formed fully functional cartilage is possible, remains one of the unsolved problems in orthopaedic practice. These knee patients have more problems than patients with anterior cruciate ligament rupture and experience severe limitations in their daily life. Despite this the knowledge about the best treatment and whether surgical treatment offers a better outcome than the natural history is still not documented. A better understanding of articular cartilage biology, pathophysiology and biomechanics is definitely warranted. Research questions in the group, have been focused on improving the understanding of the cartilage repair process and to figure out if mesenchymal stem cells should be used instead of chondrocytes for cartilage repair. The ongoing work of the cartilage research group can be divided in three main areas
Experimental cell-culturing cartilage research
The group has worked intensively with culturing conditions of chondrocytes by changing the physiological conditions of pH, oxygen and carbondioxide tension in order to obtain chondrocytes with a higher potential for regenerating hyaline cartilage. New chondrocyte preparation techniques for culturing for implantation where progenitor cells located in the normal hyaline articular cartilage are used does give hope for improvements of the repair tissue obtained. Mesenchymal stem cells harvested from the bone marrow implanted in hyaluronan-based scaffolds have been intensively studied in the laboratory for the production of articular hyaline cartilage specific markers. Theoretically these cells have a promising potential for repair of normal hyaline cartilage. Collaboration with the Institute of Immunology (RH) has contributed to improved cells for cell based cartilage repair and has made it possible to test and develop new scaffolds.
Pre-experimental cartilage research in an animal model
An important issue in cartilage treatment is the location of the defect in the knee and the consequence this might have for the treatment of the defect and the risk of degenerative changes. One experimental study has been performed to specifically investigate this issue. The difference in the outcome between microfracture and mosaicplasty has been difficult to evaluate clinically and an experimental study has been conducted to evaluate these clinical techniques. Changes are observed in the subchondral bone that are of concern for the long-term risk of degenerative changes in the joint. Mesenchymal stem cells implanted under a commercially available scaffold (figure 3) for repair of articular defect have been evaluated experimentally to look at feasibility of this technique and the amount of cartilage obtained in the defect [3].
 |
| Figure 3 Hyaluronic acid used as a cell scaffold for chondrocytes and mesenchymal stem cells. |
Clinical projects
The experimental work is closely connected to the clinical studies of the group and there are ongoing studies on comparison of the mosaic and microfracture techniques that now includes 6o patients. Patients with cartilage defects of the knees treated with chondrocyte implantation have been evaluated by electron microscopy biopsies to look at ultra organization of the tissue and deaths of chondrocytes (submitted paper to the KSSTA). A smaller previous clinical study investigated the results of periosteum transplantation as treatment of cartilage defects of the patella. Periosteum contains progenitor cells for cartilage repair but no clinical study has thoroughly evaluated the effects of this. Furthermore, a clinical trial investigating the clinical application of mesenchymal stem cells versus chondrocytes for treatment of articular cartilage defects of the knee has been conducted and 22 patients are already included in this project that is proposed to include 50 patients.
Deficient fracture healing
Delayed fracture healing or non-union may occur in patients with systemic diseases, with hormonal or nutritional deficiencies, or in patients taking specific medications like nonsteroidal anti-inflammatory drugs (NSAIDs and COXIBS). NSAIDs have been reported to affect bone metabolism in general, and indomethacine has been shown to reduce fracture healing experimentally, and to inhibit ectopic bone formation clinically.
In these studies we will investigate fracture healing in rats on a short time medication with an injectible COXIB. Parecoxib is a new and selective NSAID targeting cyclooxygenase- 2 (COX-2). Through their selective action these drugs are supposed to lack many of the main side effects of other NSAIDs and thereby are expected to be the drugs of choice in the near future for several patient groups. The effects on bone metabolism and healing have, however, not been elucidated. Furthermore, it has been demonstrated that COX-2 is required for both intramembranous and endochondral bone formation. Thus there are reasons for concern regarding the potential negative effects of these drugs on bone metabolism and bone repair. Concern has also been expressed about their potential negative effects on bone. The present study is designed to investigate the effects of short-term administration of parecoxib on bone healing. Based on the current knowledge our hypothesis is that the drug will delay the healing process and this has already been verified and published [1].
Another project on intramedullary nailing and external fixation in lower leg fractures evaluates bone healing by quantitative micro computer tomography (qmCT), in addition to mechanical testing and densitometric measurements. This includes the development of a segmentation technique applied to qmCT images and an investigation of the correlation between the segmented qmCT data and mechanical properties.
Tendon healing to bone surfaces/tunnels
Healing of tendon material to bony surfaces is of major importance in both shoulder and knee surgery where understanding of the biology and biomechanics in this process is a key element. A recent experimental paper from the group demonstrates that this is significantly affected by both a COX-2 inhibitor and a conventional NSAID [2]. The experimental setup is illustrated in figure 1 and 2 adapted from the published study.
 |
 |
| Figure 1. Operation technique. The Achilles tendon was pulled through a drill hole in distal tibia. |
Figure 2. Mechanical testing. The tibia was fixed in a clamp and the calcaneus was fixed in a claw. The tendon was pulled straight out by a force applied aligned with the drill hole. |
Biomaterial surface in prosthesis surgery One of the PhD projects in the group is focused on the surface material of prosthesis that probably can be increased by selecting the correct coating and biomaterial of the prosthesis. One experimental study will specifically focus on how this can be improved (figure 4).
 |
Figure 4. Illustration of four different coating of biomaterials used as test templates in the experimental trial.
|
Go back
Print this page
E-mail this page
