One year after treatment, characterized chondrocyte implantation was associated with a tissue regenerate that was superior to that after microfracture. Short-term clinical outcome was similar for both treatments. The superior structural outcome may result in improved long-term clinical benefit with characterized chondrocyte implantation. Long-term follow-up is needed to confirm these findings.

We have shown that osteogenic protein-1 (OP-1) (bone morphogenetic protein-7) is responsible for the induction of nephrogenic mesenchyme during embryonic kidney development. Gene knock-out studies showed that OP-1 null mutant mice die of renal failure within the first day of postnatal life. In the present study, we evaluated the effect of recombinant human OP-1 for the treatment of acute renal failure after 60 min bilateral renal artery occlusion in rats. Bioavailability studies in normal rats indicate that ‫ف‬ 1.4 g OP-1/ml is available in the circulation 1 min after intravenous administration of 250 g/kg, which then declines steadily with a half life of 30 min. About 0.5% of the administered OP-1 dose/g tissue is targeted for OP-1 receptors in the kidney. We show that OP-1 preserves kidney function, as determined by reduced blood urea nitrogen and serum creatinine, and increased survival rate when administered 10 min before or 1 or 16 h after ischemia, and then at 24-h intervals up to 72 h after reperfusion.

IV.

Conservative approach is usually the first choice for the management of the knee degeneration processes, especially in the phase of the disease recognized as early osteoarthritis (OA) with no clear lesions or associated abnormalities requiring to be addressed surgically. A wide spectrum of treatments is available, from non-pharmacological modalities to dietary supplements and pharmacological therapies, as well as minimally invasive procedures involving injections of various substances aiming to restore joint homeostasis and provide clinical improvement and possibly a disease-modifying effect. Numerous pharmaceuticals have been proposed, but since no therapy has shown all the characteristic of an ideal treatment, and side effects have been reported at both systemic and local level, the use of pharmacological agents should be considered with caution by assessing the risk/benefit ratio of the drugs prescribed. Both patients and physicians should have realistic outcome goals in pharmacological treatment, which should be considered together with other conservative measures. A combination of these therapeutic options is a more preferable scenario, in particular considering the evidence available for non-pharmacological management. In fact, exercise is an effective conservative approach, even if long-term effectiveness and optimal dose and administration modalities still need to be clarified. Finally, physical therapies are emerging as viable treatment options, and novel biological approaches are under study. Further studies to increase the limited medical evidence on conservative treatments, optimizing results, application modalities, indications, and focusing on early OA will be necessary in the future. Level of evidence IV.

Purpose The purpose of this study was to revise the clinical use of commercial BMP2 (Infuse) and BMP7 (Osigraft) based bone devices and explore the mechanism of action and efficacy of low BMP6 doses in a novel whole blood biocompatible device OSTEOGROW. Methods Complications from the clinical use of BMP2 and BMP7 have been systemically reviewed in light of their role in bone remodeling. BMP6 function has been assessed in Bmp6-/-mice by μCT and skeletal histology, and has also been examined in mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and osteoclasts. Safety and efficacy of OSTEOGROW have been assessed in rats and rabbits.Results Clinical use issues of BMP2 and BMP7 have been ascribed to the limited understanding of their role in bone remodeling at the time of device development for clinical trials. BMP2 and BMP7 in bone devices significantly promote bone resorption leading to osteolysis at the endosteal surfaces, while in parallel stimulating exuberant bone formation in surrounding tissues. Unbound BMP2 and BMP7 in bone devices precipitate on the bovine collagen and cause inflammation and swelling. OSTEOGROW required small amounts of BMP6, applied in a biocompatible blood coagulum carrier, for stimulating differentiation of MSCs and accelerated healing of critical size bone defects in animals, without bone resorption and inflammation. BMP6 decreased the number of Mladenka Jurin contributed equally to this paper. S. Vukicevic (*) : J. Curak : J. Brkljacic : M. Pauk : I. Erjavec : I. Dumic-Cule : R. Novak : V. Kufner : T. Bordukalo Niksic :

No abstract

Bone morphogenetic protein-7 in tendon graft integration might be successfully used in reconstructive surgery of ligaments.

We randomly assigned 17 patients with scaphoid non-union at the proximal pole to three treatment groups: (1) autologous iliac graft (n=6), (2) autologous iliac graft + osteogenic protein-1 (OP-1; n=6), and (3) allogenic iliac graft + OP-1 (n=5). Radiographic, scintigraphic, and clinical assessments were performed throughout the follow-up period of 24 months. OP-1 improved the performance of both autologous and allogenic bone implants and reduced radiographic healing time to 4 weeks compared with 9 weeks in group 1. Helical CT scans and scintigraphy showed that in OP-1-treated patients sclerotic bone was replaced by well-vascularised bone. The addition of OP-1 to allogenic bone implant equalised the clinical outcome with the autologous graft procedure. Consequently the harvesting of autologous graft can be avoided.Résumé Nous avons réparti 17 malades avec une pseudarthrose du pôle proximal du scaphoide en trois groupes aléatoires de traitement: (1) greffe autologue iliaque (n=6), (2) greffe autologue iliaque + protéine osteogenique-1 (OP-1; n=6), et (3) greffe allogène iliaque + OP-1 (n=5). L'estimation radiographique, scintigraphique et clinique a été exécutée pendant une période de suivi de 24 mois. L'OP-1 a amélioré la performance des autogreffes et des allogreffes osseuses et a réduit le temps curatif radiographique à 4 semaines, comparé à 9 semaines dans le groupe traité uniquement avec de l'os autologues. Chez les malades traités avec l'OP-1, la tomodensitométrie hélicoïdale et la scintigraphie ont montré que l'os scléreux était remplacé par de l'os bien vascularisé. L'addition d'OP-1 à la greffe allogène a égalisé le résultat clinique avec la procédure de greffe autologue et a permis de supprimer le temps de prise de greffe.