P.J. Emans

Tibial component rotation in total knee arthroplasty

BackgroundBoth the range of motion (ROM) technique and the tibial tubercle landmark (TTL) technique are frequently used to align the tibial component into proper rotational position during total knee arthroplasty (TKA).The aim of the study was to assess the intra-operative differences in tibial rotation position during computer-navigated primary TKA using either the TTL or ROM techniques. The ROM technique was hypothesized to be a repeatable method and to produce different tibial rotation positions compared to the TTL technique.MethodsA prospective, observational study was performed to evaluate the antero-posterior axis of the cut proximal tibia using both the ROM and the TTL technique during primary TKA without postoperative clinical assessment. Computer navigation was used to measure this difference in 20 consecutive knees of 20 patients who underwent a posterior stabilized total knee arthroplasty with a fixed-bearing polyethylene insert and a patella resurfacing.ResultsThe ROM technique is a repeatable method with an interclass correlation coefficient (ICC2) of 0.84 (p < 0.001). The trial tibial baseplate was on average 4.56 degrees externally rotated compared to the tubercle landmark. This difference was statistically significant (p = 0.028). The amount of maximum intra-operative flexion and the pre-operative mechanical axis were positively correlated with the magnitude of difference between the two methods.ConclusionsIt is important for the orthopaedic surgeon to realise that there is a significant difference between the TTL technique and ROM technique when positioning the tibial component in a rotational position. This difference is correlated with high maximum flexion and mechanical axis deviations.

Recurrent patella loosening and extra-articular migration after TKA.

Loosening and subsequent extra-articular migration of the patella component is a rare complication of total knee arthroplasty. We report a case of recurrent aseptic loosening and extra-articular migration of a patella component. Eventually, treatment consisted of removing the patellar component without replacement.

Cartilage Tissue Engineering; Lessons Learned From Periosteum

Cartilage, due to its unique physiology (lack of vasculature), can be potentially repaired using tissue engineered in the laboratory, by combining cells and with a supporting scaffold. This requires a marriage between material science, cell biology, and translational medicine, a concept well established as Tissue Engineering. Over the years the in vivo and in vitro chondrogenic potential of periosteum has been recognised by many researchers and as such periosteum is explored both to repair cartilage defects directly by transplanting periosteum into the cartilage defect or by using periosteum as a cell source for cartilage engineering purposes. The initial example hereof is the first generation of Autologous Chondrocyte Transplantation. Graft hypertrophy and ossification remain the primary drawbacks of cartilage repair strategies using engineered cartilage. These drawbacks may (partially) be due to the endochondral ossification process that can take over when cartilage is repaired. In this process chondrogenesis of progenitor cells is followed by hypertrophy of these cells and subsequent ossification. Periosteal progenitor cells go through this process in order to heal bone fractures. This review provides an overview of the role of periosteum in cartilage repair and cartilage tissue engineering and illustrates how periosteum can be used as a model to study the endochondral process. Such studies may provide clues to further optimize cartilage tissue engineering by identifying important factors which are capable of maintaining cells in their chondrogenic phenotype. Finally, the use of periosteum to engineer cartilage in vivo at an extra-articular site is described.

Identification of BMP-7-mimicking peptides that reverse the katabolic-chondrocyte phenotype in OA chondrocytes

Osteoarthritis (OA) is the most common degenerative joint disease causing joint immobility and chronic pain. Treatment is mainly based on alleviating pain and reducing disease progression. During OA progression the chondrocyte undergoes a hypertrophic switch in which extracellular matrix (ECM) -degrading enzymes are released, actively degrading the ECM. However, cell biological based therapies to slow down or reverse this katabolic phenotype are still to be developed. Bone morphogenetic protein 7 (BMP-7) has been shown to have OA disease-modifying properties. BMP-7 suppresses the chondrocyte hypertrophic and katabolic phenotype and may be the first biological treatment to target the chondrocyte phenotype in OA. However, intra-articular use of BMP-7 is at risk in the proteolytic and hydrolytic joint-environment. Weekly intra-articular injections are necessary to maintain biological activity, a frequency unacceptable for clinical use. Additionally, production of GMP-grade BMP-7 is challenging and expensive....

Celecoxib-mediated reduction of prostanoid release in Hoffa's fat pad from donors with cartilage pathology results in an attenuated inflammatory phenotype

OBJECTIVE The Hoffas fat pad (HFP) is an intra-articular adipose tissue which is situated under and behind the patella. It contains immune cells next to adipocytes and secretes inflammatory factors during osteoarthritis (OA). In this study, we compared the release profile of prostanoids, which are involved in inflammation, of HFP from OA patients vs patients with a focal cartilage defect (CD) without evidence for OA on MRI and investigated the prostanoid modulatory anti-inflammatory action of celecoxib on HFP. DESIGN Prostanoid release was analyzed in conditioned medium of HFP explant cultures from 17 osteoarthritic patients and 12 CD patients, in the presence or absence of celecoxib. Furthermore, gene expression of COX enzymes and expression of genes indicative of a pro-inflammatory or anti-inflammatory phenotype of HFP was analyzed. RESULTS Prostanoid release by HFP from knee OA patients clustered in two subgroups with high and low prostanoid producers. HFP from high prostanoid producers released higher amounts of PGE2, PGF2α and PGD2 compared to HFP from CD patients. PGE2 release by OA HFP was positively associated with expression of genes known to be expressed by M1 macrophages, indicating a role for macrophages. Celecoxib modulated prostanoid release by HFP, and also modulated the inflammation ratio towards a more favorable anti-inflammatory M2 phenotype, most effectively in patients with higher prostanoid release profiles. CONCLUSION In knee OA patients with inflamed HFPs, celecoxib may exert positive effects in the knee joint via decreasing the release of prostanoids produced by the HFP and by favorably modulating the anti-inflammatory marker expression in HFP.

Endochondral Bone Formation as Blueprint for Regenerative Medicine

During our life moving, walking, sport, etc., are essential for our health and quality of life. Both bones and cartilage enable us to do so. Bones support us, allow muscles to move them, and protect vital internal organs. At the end of most bones articular joints are situated. The side where 2 bones form an articular joint, the ends of these bones are covered with hyaline cartilage. This articular cartilage is able to withstand very high mechanical forces with very low friction and thereby enables easy movement. A large number of bones are formed by a process called endochondral ossification. During this process a cartilage template is replaced by bone, in contrast with the cartilage in newly formed joints which remains cartilage. Both articular cartilage and bone mature and this leads to a well organised architecture and specialisation. The arcade-like architecture of cartilage is capable to withstand an enormous amount of intensive and repetitive forces during life. However, the British surgeon William Hunter made the now famous statement that “From Hippocrates to the present age it is universally allowed that ulcerated cartilage is a troublesome thing and that once destroyed it is not repaired” (Hunter 1743). In contrast, bone has a very high regenerative capacity. This difference in self-healing capacity may partially be explained by the access to progenitor cells which contribute to tissue repair. For bone repair, progenitor cells of three different sources have been identified. These sources are: (i) progenitor cells form the blood stream since bone is a highly vascularised tissue, (ii) progenitor cells from the overlying periosteum and (iii) progenitor cells from the bone marrow. Cartilage is not vascularised, is not covered by periosteum, nor has a specialized tissue such as bone marrow and this might be part of the explanation for the limited self-repair capacity of cartilage. Although both tissues start from the same mesenchymal cell condensations, the contrast in self-repair is striking (Hunziker, Kapfinger et al. 2007).

168 AN EARLY INFLAMMATORY RESPONSE DETERMINES THE ONSET OF CHONDROGENESIS

chondrocyte cultures. Genes already associated with hypertrophic cartilage or OA (ALPL, COL3A1, COL10A1, MMP13, POSTN, PTH1R, RUNX2) were not significantly regulated between the two donor groups. The expression of 661 genes was differentially regulated between OA and ND chondrocytes cultured in monolayer. During scaffold culture, the differences diminished, and only 184 genes were differentially regulated. Conclusions: All in all, our data confirm already known data on many characteristic features of native OA cartilage, but we have also identified new candidate genes that are differentially expressed during OA. For the development of new OA cartilage treatment strategies, such a deeper insight into phenotypical alterations occurring in OA is important. Only a few genes were differentially expressed between OA and ND chondrocytes in hyaff-11 culture. So, the risk of generating hypertrophic cartilage does not seem to be increased for OA chondrocytes. Importantly, our findings suggest that the chondrogenic capacity is not significantly affected by OA, and OA chondrocytes fulfill the requirements for ACT.

Cell Based Therapies: What Do We Learn from Periosteal Osteochondrogenesis?

Unraveling isolation, cultivation and transplantation protocols is often difficult and time consuming but essential to exploit the full potential of cell based therapies. Studying periosteal callus formation, may give novel insights how this tissue can be used to repair cartilage and bone defects and thus bypass optimization of the protocols mentioned above. Periosteal callus can be induced in vivo without breaking the bone. During periosteal callus formation, osteochondrogenic progenitor cells which reside in the cambium cambium layer, differentiate via the sequential steps of endochondral bone formation; chondrogenesis is initiated then chondrocytes differentiate into hypertrophic cells. These hypertrophic chondrocytes release pro-angiogenic factors, mineralize and bone is deposited. Grafts can be harvested during the chondrogenic phase. Compared to isolated undifferentiated periosteal cells, cells in these grafts survive the transplantation into an osteochondral defect much better. By injecting a gel between bone and periosteum, the micro-environment can be manipulated. Per example inhibition of vascularization and induction of hypoxia enhances periosteal chondrogenesis both in vitro and in vivo. Taken together, studying repair processes of the body in detail may not only give essential information for different cell based therapies, but can even lead to a complete other approach in which the body its own regenerative capacity is used.

175 DECREASED CHONDROCYTE HYPERTROPHIC DIFFERENTIATION BY INHIBITION OF CYCLOOXYGENASE-2

INTRODUCTION: Chondrocyte hypertrophic differentiation is an essential process during endochondral bone formation, however it hampers the application of many cartilage regenerative techniques and may play a role at the onset of osteoarthritis (1). Heterotopic bone formation after orthopaedic surgery is suppressed by non-steroidal anti-inflammatory drugs (NSAIDs) and recent studies point to an essential role of Cyclooxygenase-2 (COX-2) in osteocytes during endochondral ossification (2). COX-2 and its metabolite PGE2 are thought to regulate the function of bone morphogenic protein-2 (BMP-2) and vice versa, which might provide an explanation for the role of COX-2 during endochondral ossification (3). It is largely unknown how and in which phase NSAIDs affect endochondral bone formation. In this study, we aim to determine the involvement of COX-2 in chondrocyte hypertrophy and provide an explanation for the suppressive effect of NSAIDs on heterotopic ossification and fracture healing. .