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Horgen / Horgen (Dorfkern), Switzerland

Martinez-Carranza N.,Karolinska University Hospital | Martinez-Carranza N.,Karolinska Institutet | Berg H.E.,Karolinska University Hospital | Berg H.E.,Karolinska Institutet | And 4 more authors.
Osteoarthritis and Cartilage | Year: 2014

Objective: Focal cartilage lesions according to International Cartilage Repair Society (ICRS) grade 3-4 in the medial femoral condyle may progress to osteoarthritis. When treating such focal lesions with metallic implants a sound fixation to the underlying bone is mandatory. We developed a monobloc unipolar cobalt-chrome (Co-Cr) implant with a double coating; first a layer of commercially pure titanium (c.p.Ti) on top of which a layer of hydroxyapatite (HA) was applied. We hypothesised that such a double coating would provide long-lasting and adequate osseointegration. Design (materials and methods): Unilateral medial femoral condyles of 10 sheep were operated. The implants were inserted in the weight-bearing surface and immediate weight-bearing was allowed. Euthanasia was performed at 6 (three animals) or 12 months (six animals). Osseointegration was analysed with micro-computer tomography (CT), light microscopy and histomorphometric analyses using backscatter scanning electron microscopy (B-SEM) technique. Results: At 6 months one specimen out of three showed small osteolytic areas at the hat and at 12 months two specimens out of six showed small osteolytic areas at the hat, no osteolytical areas were seen around the peg at any time point. At both time points, a high total bone-to-implant contact was measured with a mean (95% confidence interval - CI) of 90.6 (79-102) at 6 months and 92.3 (89-95) at 12 months, respectively. Conclusions: A double coating (Ti+HA) of a focal knee resurfacing Co-Cr implant was presented in a sheep animal model. A firm and consistent bond to bone under weight-bearing conditions was shown up to 1 year. © 2014 Osteoarthritis Research Society International. Source

Martinez-Carranza N.,Karolinska University Hospital | Martinez-Carranza N.,Karolinska Institutet | Ryd L.,Episurf Medical AB | Hultenby K.,Karolinska Institutet | And 7 more authors.
Osteoarthritis and Cartilage | Year: 2016

Background: Full depth focal cartilage lesions do not heal spontaneously and while some of these lesions are asymptomatic they might progress to osteoarthritis. Treatment for these lesions is warranted and the gold standard treatment at younger age remains biological healing by cell stimulation. In the middle-age patient the success rate of biologic treatment varies, hence the surge of non-biological alternatives. Our objective was to evaluate the efficacy and safety of a metallic implant for treatment of these lesions with respect to the long-term panarticular cartilage homeostasis. Methods: The medial femoral condyle of 16 sheep was operated unilaterally. A metallic implant was inserted in the weight-bearing surface at an aimed height of 0.5 mm recessed. Euthanasia was performed at 6 or 12 months. Implant height and tilt was analyzed using a laser-scanning device. Damage to cartilage surfaces was evaluated macroscopically and microscopically according to the Osteoarthritis Research Society International (OARSI) recommendations. Results: Thirteen sheep were available for evaluation and showed a varying degree of cartilage damage linearly increasing with age. Cartilage damage of the medial tibial plateau opposing the implant was increased compared to the non-operated knee by 1.77 units (p = 0.041; 95% CI: 0.08, 3.45) on a 0-27 unit scale. Remaining joint compartments were unaffected. Implant position averaged 0.54 recessed (95% CI: 0.41, 0.67). Conclusions: Our results showed a consistent and accurate placement of these implants at a defined zone. At this position cartilage wear of opposing and surrounding joint cartilage is limited. Thus expanded animal and human studies are motivated. © 2015 The Authors. Source

Bain J.L.,University of Alabama at Birmingham | Bonvallet P.P.,University of Alabama at Birmingham | Abou-Arraj R.V.,University of Alabama at Birmingham | Schupbach P.,Schupbach Ltd. | And 2 more authors.
Tissue Engineering - Part A | Year: 2015

Autogenous bone is the gold standard material for bone grafting in craniofacial and orthopedic regenerative medicine. However, due to complications associated with harvesting donor bone, clinicians often use commercial graft materials that may lose their osteoinductivity due to processing. This study was aimed to functionalize one of these materials, anorganic bovine bone (ABB), with osteoinductive peptides to enhance regenerative capacity. Two peptides known to induce osteoblastic differentiation of mesenchymal stem cells were evaluated: (1) DGEA, an amino acid motif within collagen I and (2) a biomimetic peptide derived from bone morphogenic protein 2 (BMP2pep). To achieve directed coupling of the peptides to the graft surface, the peptides were engineered with a heptaglutamate domain (E7), which confers specific binding to calcium moieties within bone mineral. Peptides with the E7 domain exhibited greater anchoring to ABB than unmodified peptides, and E7 peptides were retained on ABB for at least 8 weeks in vivo. To assess the osteoinductive potential of the peptide-conjugated ABB, ectopic bone formation was evaluated utilizing a rat subcutaneous pouch model. ABB conjugated with full-length recombinant BMP2 (rBMP2) was also implanted as a model for current clinical treatments utilizing rBMP2 passively adsorbed to carriers. These studies showed that E7BMP2pep/ABB samples induced more new bone formation than all other peptides, and an equivalent amount of new bone as compared with rBMP2/ABB. A mandibular defect model was also used to examine intrabony healing of peptide-conjugated ABB. Bone healing was monitored at varying time points by positron emission tomography imaging with 18F-NaF, and it was found that the E7BMP2pep/ABB group had greater bone metabolic activity than all other groups, including rBMP2/ABB. Importantly, animals implanted with rBMP2/ABB exhibited complications, including inflammation and formation of cataract-like lesions in the eye, whereas no side effects were observed with E7BMP2pep/ABB. Furthermore, histological analysis of the tissues revealed that grafts with rBMP2, but not E7BMP2pep, induced formation of adipose tissue in the defect area. Collectively, these results suggest that E7-modified BMP2-mimetic peptides may enhance the regenerative potential of commercial graft materials without the deleterious effects or high costs associated with rBMP2 treatments. © Copyright 2015, Mary Ann Liebert, Inc. Source

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