TY  - JOUR
A1  - Bothe, Friederike
A1  - Deubel, Anne-Kathrin
A1  - Hesse, Eliane
A1  - Lotz, Benedict
A1  - Groll, Jürgen
A1  - Werner, Carsten
A1  - Richter, Wiltrud
A1  - Hagmann, Sebastien
T1  - Treatment of focal cartilage defects in minipigs with zonal chondrocyte/mesenchymal progenitor cell constructs
JF  - International Journal of Molecular Sciences
N2  - Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (µCT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage.
KW  - cartilage repair
KW  - osteochondral defect
KW  - tissue engineering
KW  - starPEG hydrogel
KW  - chondrocyte
KW  - MSC
KW  - zonal construct
KW  - minipig
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285118
SN  - 1422-0067
VL  - 20
IS  - 3
ER  - 
TY  - JOUR
A1  - Stuckensen, Kai
A1  - Lamo-Espinosa, José M.
A1  - Muiños-López, Emma
A1  - Ripalda-Cemboráin, Purificación
A1  - López-Martínez, Tania
A1  - Iglesias, Elena
A1  - Abizanda, Gloria
A1  - Andreu, Ion
A1  - Flandes-Iparraguirre, María
A1  - Pons-Villanueva, Juan
A1  - Elizalde, Reyes
A1  - Nickel, Joachim
A1  - Ewald, Andrea
A1  - Gbureck, Uwe
A1  - Prósper, Felipe
A1  - Groll, Jürgen
A1  - Granero-Moltó, Froilán
T1  - Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP−2 and enhanced bone regeneration
JF  - Materials
N2  - In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP–2, BMP–7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP–2. In vitro, both scaffolds presented similar mechanical properties, rhBMP–2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP–2 mediated bone healing.
KW  - rhBMP–2
KW  - collagen sponge
KW  - cryostructured scaffolds
KW  - bone critical size defect
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195966
SN  - 1996-1944
VL  - 12
IS  - 19
ER  -