T.J. Welting

Novel radiopaque ultrahigh molecular weight polyethylene sublaminar wires in a growth-guidance system for the treatment of early-onset scoliosis: feasibility in a large animal study.

Study Design. In vivo analysis in an ovine model. Objective. To evaluate the feasibility of radiopaque ultrahigh molecular weight polyethylene (UHMWPE) sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility, and growth potential. Summary of Background Data. Several growth-guidance systems have been developed for the treatment of early-onset scoliosis. The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for early-onset scoliosis. Methods. Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHMWPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T12 and fixed to dual cobalt-chromium rods. Four age-matched animals that were not operated were evaluated to serve as a control group. Radiographs were obtained to measure growth of the instrumented segment. After 24 weeks, the animals were killed and the spines were harvested for histological evaluation and high-resolution peripheral quantitative computed tomographic analysis. Results. No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5–T11) in the intervention group (27 ± 2 mm), which was not significantly different to the control group, (30 ± 4 mm, P = 0.42). High-resolution peripheral quantitative computed tomographic analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris. Conclusion. This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth-guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local-tissue response to these wires was observed. Level of Evidence: N/ASTUDY DESIGN In vivo analysis in an ovine model. OBJECTIVE To evaluate the feasibility of radiopaque ultrahigh molecular weight polyethylene (UHMWPE) sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility, and growth potential. SUMMARY OF BACKGROUND DATA Several growth-guidance systems have been developed for the treatment of early-onset scoliosis. The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for early-onset scoliosis. METHODS Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHMWPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T12 and fixed to dual cobalt-chromium rods. Four age-matched animals that were not operated were evaluated to serve as a control group. Radiographs were obtained to measure growth of the instrumented segment. After 24 weeks, the animals were killed and the spines were harvested for histological evaluation and high-resolution peripheral quantitative computed tomographic analysis. RESULTS No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5-T11) in the intervention group (27 ± 2 mm), which was not significantly different to the control group, (30 ± 4 mm, P = 0.42). High-resolution peripheral quantitative computed tomographic analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris. CONCLUSION This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth-guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local-tissue response to these wires was observed. LEVEL OF EVIDENCE N/A.

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....

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.

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. .